1.Physiological and transcriptional responses to heat stress in a typical phenotype of Pinellia ternata.
Jialu WANG ; Jialei CHEN ; Xiangyu ZHANG ; Xue FENG ; Xiwen LI
Chinese Journal of Natural Medicines (English Ed.) 2023;21(4):243-252
		                        		
		                        			
		                        			Pinellia ternata is an important medicinal plant, and its growth and development are easily threatened by high temperature. In this study, comprehensive research on physiological, cytological and transcriptional responses to different levels of heat stress were conducted on a typical phenotype of P. ternata. First, P. ternata exhibited tolerance to the increased temperature, which was supported by normal growing leaves, as well as decreased and sustained photosynthetic parameters. Severe stress aggravated the damages, and P. ternata displayed an obvious leaf senescence phenotype, with significantly increased SOD and POD activities (46% and 213%). In addition, mesophyll cells were seriously damaged, chloroplast thylakoid was fuzzy, grana lamellae and stroma lamellae were obviously broken, and grana thylakoids were stacked, resulting in a dramatically declined photosynthetic rate (74.6%). Moreover, a total of 16 808 genes were significantly differential expressed during this process, most of which were involved in photosynthesis, transmembrane transporter activity and plastid metabolism. The number of differentially expressed transcription factors in MYB and bHLH families was the largest, indicating that these genes might participate in heat stress response in P. ternata. These findings provide insight into the response to high temperature and facilitate the standardized cultivation of P. ternata.
		                        		
		                        		
		                        		
		                        			Pinellia/genetics*
		                        			;
		                        		
		                        			Heat-Shock Response/genetics*
		                        			;
		                        		
		                        			Photosynthesis/genetics*
		                        			;
		                        		
		                        			Plants, Medicinal/genetics*
		                        			;
		                        		
		                        			Phenotype
		                        			
		                        		
		                        	
2.Study on drug properties of Arisaematis Rhizoma and Arisaema Cum Bile based on substance and energy metabolism in normal and cold/heat syndrome model rats.
Fa-Zhi SU ; Chen-Xi BAI ; Wen-Sen ZHANG ; Jing YANG ; Jian-Ping HU ; Yan-Ping SUN ; Bing-You YANG ; Hai-Xue KUANG ; Qiu-Hong WANG
China Journal of Chinese Materia Medica 2022;47(17):4682-4690
		                        		
		                        			
		                        			This paper clarified the scientific connotation of the changes in cold and heat properties of Arisaematis Rhizoma and Arisaema Cum Bile through investigating the changes of substance and energy metabolism after drug intervention in the rats with normal and cold/heat syndrome, so as to improve the method of evaluating the drug properties of Chinese medicine. After one week of adaptive feeding, healthy male SD rats were randomly divided into three parts: normal rats, heat syndrome rat models, and cold syndrome rat models. Through ice water bath and oral euthyrox(120 μg·kg~(-1)), the models of cold syndrome and heat syndrome were induced, respectively. The models were made at 9:00 am. and administrated by gavage at 3:00 pm. every day. All administration groups were administrated with Arisaematis Rhizoma and Arisaema Cum Bile decoction, respectively, and the blank group was given the same dose of normal saline. After continuous administration for 15 d, the rats were anesthetized by chloral hydrate, blood was taken from abdominal aorta, and the hearts and livers were removed and stored at-80 ℃. The changes in the body weight and anal temperature of rats during administration were detected, and the liver coefficient of rats was detected after removing the liver. Enzyme-linked immunosorbent assay(ELISA) was adopted to detect the expression level of the indexes related to substance and energy metabolism in liver and heart of rat, and Western blot was used to detect the expression of key proteins in AMPK/mTOR signaling pathway for further verification. The results showed that Arisaematis Rhizoma enhanced the expression level of enzymes related to substance and energy metabolism in the normal and cold and heat syndrome rat models, and increased anal temperature, which exhibited warm(hot) drug property. Arisaema Cum Bile inhibited the level of substance and energy metabolism in rats, and reduced anal temperature, which showed cold(cool) drug property. Chinese Pharmacopoeia has recorded "Arisaematis Rhizoma has warm property and Arisaema Cum Bile has cool property", which is consistent with the phenomenon in this study. Therefore, it is feasible to evaluate the drug properties of Chinese medicine based on the substance and energy metabolism of normal and cold/heat syndrome model rats, which completes the method of evaluating drug properties of Chinese medicine.
		                        		
		                        		
		                        		
		                        			AMP-Activated Protein Kinases
		                        			;
		                        		
		                        			Animals
		                        			;
		                        		
		                        			Arisaema/chemistry*
		                        			;
		                        		
		                        			Bile
		                        			;
		                        		
		                        			Chloral Hydrate
		                        			;
		                        		
		                        			Cold-Shock Response/drug effects*
		                        			;
		                        		
		                        			Drugs, Chinese Herbal/therapeutic use*
		                        			;
		                        		
		                        			Energy Metabolism
		                        			;
		                        		
		                        			Heat Stroke/therapy*
		                        			;
		                        		
		                        			Hot Temperature
		                        			;
		                        		
		                        			Male
		                        			;
		                        		
		                        			Rats
		                        			;
		                        		
		                        			Rats, Sprague-Dawley
		                        			;
		                        		
		                        			Saline Solution
		                        			;
		                        		
		                        			Syndrome
		                        			;
		                        		
		                        			TOR Serine-Threonine Kinases
		                        			;
		                        		
		                        			Thyroxine
		                        			;
		                        		
		                        			Water
		                        			
		                        		
		                        	
3.Dynamic changes of the PGAM1 expression in the mouse testis exposed to single heat stress.
Yuan-Shu ZHAO ; Wen-Bin CHEN ; Li-Bin ZOU ; Dao-Jun L ; Shou-Bo ZHANG
National Journal of Andrology 2021;27(9):780-786
		                        		
		                        			Objective:
		                        			To investigate the expression of phosphoglycerate mutase 1 (PGAM1) in the mouse testis after exposure to single heat stress (SHS).
		                        		
		                        			METHODS:
		                        			We randomly assigned 32 C57 male mice to an SHS (n = 16) and a control group (n = 16), the former bathed in water at 43 ℃ and the latter at 25 ℃ for 15 minutes. At 1 and 7 days after exposure, we harvested the testicular tissue for observation of the morphological changes of testicular cells by HE staining and determination of the location and expression of the PGAM1 protein by immunohistochemistry and Western blot.
		                        		
		                        			RESULTS:
		                        			The testis volume of the mice were reduced significantly, the spermatogenic tubules were disorganized, and the cells were reduced in number after heat stress and basically disappeared after 7 days. Immunohistochemistry showed extensive expression of the PGAM1 protein in the testicular spermatogenic tubules of the SHS-exposed mice, significantly higher than in the control group at 1 day after exposure, which was down-regulated in the testis tissue at 7 days, but still markedly higher than that in the control. Western blot exhibited significantly up-regulated expression of the PGAM1 protein after heat stress compared with that in the control group.
		                        		
		                        			CONCLUSIONS
		                        			The expression of the PGAM1 protein undergoes dynamic changes in the mouse testis after exposed to single heat stress, which is related to heat stress-induced proliferation and division of testicular spermatogenic cells.
		                        		
		                        		
		                        		
		                        			Animals
		                        			;
		                        		
		                        			Heat-Shock Response
		                        			;
		                        		
		                        			Male
		                        			;
		                        		
		                        			Mice
		                        			;
		                        		
		                        			Phosphoglycerate Mutase
		                        			;
		                        		
		                        			Testis
		                        			
		                        		
		                        	
4.Development and validation of an environmental heat strain risk assessment (EHSRA) index using structural equation modeling based on empirical relations.
Saeid YAZDANIRAD ; Farideh GOLBABAEI ; Abbas Rahimi FOROUSHANI ; Mohammad Reza MONAZZAM ; Habibollah DEHGHAN
Environmental Health and Preventive Medicine 2020;25(1):63-63
		                        		
		                        			BACKGROUND:
		                        			Need to a simple, available, accurate, comprehensive, and valid indicator is felt to assess thermal effects. Therefore, the present study was aimed to develop and validate the environmental heat strain risk assessment (EHSRA) index using structural equation modeling (SEM) based on empirical relations.
		                        		
		                        			METHODS:
		                        			This cross-sectional study was performed on 201 male workers in environments with various climatic conditions. The heart rate and tympanic temperature of the individuals were monitored at times of 30, 60, and 90 min after beginning the work. At these times, values of dry temperature, wet temperature, globe temperature, and air velocity were also measured and metabolism rate and clothing thermal insulation value were estimated. At the end, a theoretical model was depicted in AMOS software and obtained coefficients were applied to develop a novel index. The scores of this indicator were categorized into four risk levels via ROC curves and validate using linear regression analysis.
		                        		
		                        			RESULTS:
		                        			Indirect effect coefficients of the globe temperature, dry temperature, wet temperature, air velocity, metabolism, and clothing thermal insulation variables on the tympanic temperature were computed by 0.77, 0.75, 0.69, 0.24, 0.49, and 0.39, respectively. These coefficients were applied to develop the index. Optimal cut-off points of boundaries between risk levels included 12.02, 15.88, and 17.56. The results showed that the EHSRA index justified 75% of the variations of the tympanic temperature (R
		                        		
		                        			CONCLUSIONS
		                        			The novel index possesses appropriate validity. It was suggested that this indicator is applied and validated in various environments in the next studies.
		                        		
		                        		
		                        		
		                        			Adult
		                        			;
		                        		
		                        			Environmental Health/methods*
		                        			;
		                        		
		                        			Heat-Shock Response
		                        			;
		                        		
		                        			Hot Temperature/adverse effects*
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Iran
		                        			;
		                        		
		                        			Latent Class Analysis
		                        			;
		                        		
		                        			Male
		                        			;
		                        		
		                        			Middle Aged
		                        			;
		                        		
		                        			Risk Assessment/methods*
		                        			;
		                        		
		                        			Young Adult
		                        			
		                        		
		                        	
5.Transformation and attribution of drug properties in Galla Chinesis fermented Baiyaojian based on cold and heat syndrome rats.
Rui-Sheng WANG ; Zhen-Ling ZHANG ; Yi-Tian CHEN ; Yun-Ling XIA ; Xiu-Min LIN ; Jiang-Shan ZHANG ; Meng-Zhen YAN
China Journal of Chinese Materia Medica 2019;44(10):2084-2089
		                        		
		                        			
		                        			To reveal the transformation and attribution of drug properties in Galla Chinesis fermented Baiyaojian by studying the effect of Galla Chinesis and Baiyaojian on cold and heat syndrome rats. Euthyrox was used to induce the hyperthyrosis model,ice water stimulation was used to induce the cold syndrome model,and different concentrations of Galla Chinesis and Baiyaojian water decoction were administrated by gavage for 15 d continuously. Symptom indexes were evaluated,content of pyruvic acid( PA),ATPase activity in liver and contents of DA,T4,cAMP,5-HT,NE,17-OHCS,TRH and TSH in serum were assayed by enzyme linked immunosorbent assay and spectrophotometry. The rectal temperature,water consumption and body weight of heat syndrome rats in model group were increased,cAMP,NE,17-OHCS,TRH and PA were increased,TSH,Na-K ATPase and Ca-Mg ATPase were increased significantly( P<0. 01),while 5-HT was decreased,compared with those of the blank group( P< 0. 05),the contents of T4,DA,NE,TSH,TRH,cAMP and 17-OHCS were decreased significantly( P<0. 01),PA and Ca-Mg ATPase in WG and BG groups were decreased compared with those of the model group( P<0. 05),and the Galla Chinesis content of WG group was lower than that of BG group,while the contents of 5-HT in WG and BG groups were increased,and the Galla Chinesis content of WG group was higher than that of BG group,with no significant difference of viscera index between heat syndrome rats in blank group,model group and drug groups. The rectal temperature,water consumption and body weight of cold syndrome rats in model group were decreased,DA,T4,cAMP,NE,17-OHCS,TRH,TSH,PA,Na-K ATPase and Ca-Mg ATPase of rats in model group were decreased,whereas 5-HT was increased compared with those of the blank group( P<0. 05),the indexes of heart,lung and kidney were significantly higher than those in the blank group( P<0. 05). Both Galla Chinesis and Baiyaojian can significantly alleviate the symptoms of heat syndrome rats caused by levothyroxine sodium. Galla Chinesis has a better effect than Baiyaojian,but cannot alleviate the symptoms of cold syndrome caused by ice water stimulation,suggestting that the decoction of Galla Chinesis and Baiyaojian are both cold,but Galla Chinesis is colder than Baiyaojian. Cold property in Galla Chinesis fermented Baiyaojian can be relieved. In clinical application,the property of " slight cold" is more accurate than " neutral property" for Baiyaojian.
		                        		
		                        		
		                        		
		                        			Animals
		                        			;
		                        		
		                        			Cold Temperature
		                        			;
		                        		
		                        			Cold-Shock Response
		                        			;
		                        		
		                        			Drugs, Chinese Herbal
		                        			;
		                        		
		                        			pharmacology
		                        			;
		                        		
		                        			Heart
		                        			;
		                        		
		                        			Heat-Shock Response
		                        			;
		                        		
		                        			Hot Temperature
		                        			;
		                        		
		                        			Kidney
		                        			;
		                        		
		                        			Liver
		                        			;
		                        		
		                        			Lung
		                        			;
		                        		
		                        			Medicine, Chinese Traditional
		                        			;
		                        		
		                        			Rats
		                        			
		                        		
		                        	
6.Effect of HSPB9 on Apoptosis of DF-1 Cells.
Yong Jie XU ; Mei Ling HU ; Liang Hui ZHOU ; Qi WANG ; Xi Quan ZHANG ; Qing Bin LUO
Biomedical and Environmental Sciences 2019;32(2):107-120
		                        		
		                        			OBJECTIVE:
		                        			Our aim was to explore whether heat stress protein (HSP) 9 preferentially expresses under heat stress and affects the expression of other heat stress proteins as well as to explore the effect of HSPB9 overexpression and knockdown on apoptosis in DF-1.
		                        		
		                        			METHODS:
		                        			We used gene cloning to construct an overexpression vector of the target gene, and synthesized the target gene interference fragment to transfect the chicken fibroblast cell line. Gene and protein expression, as well as apoptosis, were detected by RT-qPCR, Western blot, and flow cytometry.
		                        		
		                        			RESULTS:
		                        			Chicken DF-1 cells showed an early state of apoptosis in the early stages of HSPB9 overexpression. In the later stages, as HSPB9 expression increased, the cells showed inhibition of apoptosis. When the cells were under heat stress, HSPB9 expression was much higher and earlier than the expression of HSPB1 and HSPA2. In addition, high expression of HSPB9 had a negative effect on HSPB1 and HSPA2 expression. This negative feedback decreased the percentage of early stages of apoptotic cells and promoted cell survival.
		                        		
		                        			CONCLUSION
		                        			HSPB9 expression, although rapid, is detrimental to cell survival early during its overexpression. In heat stress, HSPB9 overexpression, while inhibiting the expression of HSPA2 and HSPB1, is beneficial to cell survival.
		                        		
		                        		
		                        		
		                        			Animals
		                        			;
		                        		
		                        			Apoptosis
		                        			;
		                        		
		                        			genetics
		                        			;
		                        		
		                        			Avian Proteins
		                        			;
		                        		
		                        			genetics
		                        			;
		                        		
		                        			Cell Line
		                        			;
		                        		
		                        			Chickens
		                        			;
		                        		
		                        			Heat-Shock Proteins
		                        			;
		                        		
		                        			genetics
		                        			;
		                        		
		                        			Heat-Shock Response
		                        			;
		                        		
		                        			genetics
		                        			
		                        		
		                        	
7.Heat shock protein 70 increases cell proliferation, neuroblast differentiation, and the phosphorylation of CREB in the hippocampus
Hyun Jung KWON ; Woosuk KIM ; Hyo Young JUNG ; Min Soo KANG ; Jong Whi KIM ; Kyu Ri HAHN ; Dae Young YOO ; Yeo Sung YOON ; In Koo HWANG ; Dae Won KIM
Laboratory Animal Research 2019;35(4):154-164
		                        		
		                        			
		                        			In the present study, we investigated the effects of heat shock protein 70 (HSP70) on novel object recognition, cell proliferation, and neuroblast differentiation in the hippocampus. To facilitate penetration into the blood–brain barrier and neuronal plasma membrane, we created a Tat-HSP70 fusion protein. Eight-week-old mice received intraperitoneal injections of vehicle (10% glycerol), control-HSP70, or Tat-HSP70 protein once a day for 21 days. To elucidate the delivery efficiency of HSP70 into the hippocampus, western blot analysis for polyhistidine was conducted. Polyhistidine protein levels were significantly increased in control-HSP70- and Tat-HSP70-treated groups compared to the control or vehicle-treated group. However, polyhistidine protein levels were significantly higher in the Tat-HSP70-treated group compared to that in the control-HSP70-treated group. In addition, immunohistochemical study for HSP70 showed direct evidences for induction of HSP70 immunoreactivity in the control-HSP70- and Tat-HSP70-treated groups. Administration of Tat-HSP70 increased the novel object recognition memory compared to untreated mice or mice treated with the vehicle. In addition, the administration of Tat-HSP70 significantly increased the populations of proliferating cells and differentiated neuroblasts in the dentate gyrus compared to those in the control or vehicle-treated group based on the Ki67 and doublecortin (DCX) immunostaining. Furthermore, the phosphorylation of cAMP response element-binding protein (pCREB) was significantly enhanced in the dentate gyrus of the Tat-HSP70-treated group compared to that in the control or vehicle-treated group. Western blot study also demonstrated the increases of DCX and pCREB protein levels in the Tat-HSP70-treated group compared to that in the control or vehicle-treated group. In contrast, administration of control-HSP70 moderately increased the novel object recognition memory, cell proliferation, and neuroblast differentiation in the dentate gyrus compared to that in the control or vehicle-treated group. These results suggest that Tat-HSP70 promoted hippocampal functions by increasing the pCREB in the hippocampus.
		                        		
		                        		
		                        		
		                        			Animals
		                        			;
		                        		
		                        			Blotting, Western
		                        			;
		                        		
		                        			Cell Membrane
		                        			;
		                        		
		                        			Cell Proliferation
		                        			;
		                        		
		                        			Cyclic AMP Response Element-Binding Protein
		                        			;
		                        		
		                        			Dentate Gyrus
		                        			;
		                        		
		                        			Heat-Shock Proteins
		                        			;
		                        		
		                        			Hippocampus
		                        			;
		                        		
		                        			Hot Temperature
		                        			;
		                        		
		                        			HSP70 Heat-Shock Proteins
		                        			;
		                        		
		                        			Injections, Intraperitoneal
		                        			;
		                        		
		                        			Memory
		                        			;
		                        		
		                        			Mice
		                        			;
		                        		
		                        			Neurons
		                        			;
		                        		
		                        			Phosphorylation
		                        			
		                        		
		                        	
8.Heat Shock Factor 1 Predicts Poor Prognosis of Gastric Cancer.
Seok Jun KIM ; Seok Cheol LEE ; Hyun Gu KANG ; Jungsoo GIM ; Kyung Hwa LEE ; Seung Hyun LEE ; Kyung Hee CHUN
Yonsei Medical Journal 2018;59(9):1041-1048
		                        		
		                        			
		                        			PURPOSE: Heat shock factor 1 (HSF1) is a key regulator of the heat shock response and plays an important role in various cancers. However, the role of HSF1 in gastric cancer is still unknown. The present study evaluated the function of HSF1 and related mechanisms in gastric cancer. MATERIALS AND METHODS: The expression levels of HSF1 in normal and gastric cancer tissues were compared using cDNA microarray data from the NCBI Gene Expression Omnibus (GEO) dataset. The proliferation of gastric cancer cells was analyzed using the WST assay. Transwell migration and invasion assays were used to evaluate the migration and invasion abilities of gastric cancer cells. Protein levels of HSF1 were analyzed using immunohistochemical staining of tissue microarrays from patients with gastric cancer. RESULTS: HSF1 expression was significantly higher in gastric cancer tissue than in normal tissue. Knockdown of HSF1 reduced the proliferation, migration, and invasion of gastric cancer cells, while HSF1 overexpression promoted proliferation, migration, and invasion of gastric cancer cells. Furthermore, HSF1 promoted the proliferation of gastric cancer cells in vivo. In Kaplan-Meier analysis, high levels of HSF1 were associated with poor prognosis for patients with gastric cancer (p=0.028). CONCLUSION: HSF1 may be closely associated with the proliferation and motility of gastric cancer cells and poor prognosis of patients with gastric cancer. Accordingly, HSF1 could serve as a prognostic marker for gastric cancer.
		                        		
		                        		
		                        		
		                        			Dataset
		                        			;
		                        		
		                        			Gene Expression
		                        			;
		                        		
		                        			Heat-Shock Response
		                        			;
		                        		
		                        			Hot Temperature*
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Kaplan-Meier Estimate
		                        			;
		                        		
		                        			Oligonucleotide Array Sequence Analysis
		                        			;
		                        		
		                        			Prognosis*
		                        			;
		                        		
		                        			Shock*
		                        			;
		                        		
		                        			Stomach Neoplasms*
		                        			
		                        		
		                        	
9.Effect of a combination of astaxanthin supplementation, heat stress, and intermittent reloading on satellite cells during disuse muscle atrophy.
Toshinori YOSHIHARA ; Takao SUGIURA ; Nobuyuki MIYAJI ; Yuki YAMAMOTO ; Tsubasa SHIBAGUCHI ; Ryo KAKIGI ; Hisashi NAITO ; Katsumasa GOTO ; Daijiro OHMORI ; Toshitada YOSHIOKA
Journal of Zhejiang University. Science. B 2018;19(11):844-852
		                        		
		                        			
		                        			We examined the effect of a combination of astaxanthin (AX) supplementation, repeated heat stress, and intermittent reloading (IR) on satellite cells in unloaded rat soleus muscles. Forty-nine male Wistar rats (8-week-old) were divided into control, hind-limb unweighting (HU), IR during HU, IR with AX supplementation, IR with repeated heat stress (41.0-41.5 °C for 30 min), and IR with AX supplementation and repeated heat stress groups. After the experimental period, the antigravitational soleus muscle was analyzed using an immunohistochemical technique. Our results revealed that the combination of dietary AX supplementation and heat stress resulted in protection against disuse muscle atrophy in the soleus muscle. This protective effect may be partially due to a higher satellite cell number in the atrophied soleus muscle in the IR/AX/heat stress group compared with the numbers found in the other groups. We concluded that the combination treatment with dietary AX supplementation and repeated heat stress attenuates soleus muscle atrophy, in part by increasing the number of satellite cells.
		                        		
		                        		
		                        		
		                        			Animals
		                        			;
		                        		
		                        			Body Weight
		                        			;
		                        		
		                        			Dietary Supplements
		                        			;
		                        		
		                        			Fibrinolytic Agents/pharmacology*
		                        			;
		                        		
		                        			Heat-Shock Response
		                        			;
		                        		
		                        			Hindlimb
		                        			;
		                        		
		                        			Hot Temperature
		                        			;
		                        		
		                        			Immunohistochemistry
		                        			;
		                        		
		                        			Male
		                        			;
		                        		
		                        			Muscle, Skeletal
		                        			;
		                        		
		                        			Muscular Atrophy/drug therapy*
		                        			;
		                        		
		                        			Oxidative Stress
		                        			;
		                        		
		                        			Rats
		                        			;
		                        		
		                        			Rats, Wistar
		                        			;
		                        		
		                        			Satellite Cells, Skeletal Muscle/cytology*
		                        			;
		                        		
		                        			Xanthophylls/pharmacology*
		                        			
		                        		
		                        	
10.Endoplasmic Reticulum Stress Induces the Early Appearance of Pro-apoptotic and Anti-apoptotic Proteins in Neurons of Five Familial Alzheimer's Disease Mice.
Hui SHEN ; Xiao-Dong PAN ; Jing ZHANG ; Yu-Qi ZENG ; Meng ZHOU ; Lu-Meng YANG ; Bing YE ; Xiao-Man DAI ; Yuan-Gui ZHU ; Xiao-Chun CHEN ;
Chinese Medical Journal 2016;129(23):2845-2852
BACKGROUNDAmyloid β (Aβ) deposits and the endoplasmic reticulum stress (ERS) are both well established in the development and progression of Alzheimer's disease (AD). However, the mechanism and role of Aβ-induced ERS in AD-associated pathological progression remain to be elucidated.
METHODSThe five familial AD (5×FAD) mice and wild-type (WT) mice aged 2, 7, and 12 months were used in the present study. Morris water maze test was used to evaluate their cognitive performance. Immunofluorescence and Western blot analyses were used to examine the dynamic changes of pro-apoptotic (CCAAT/enhancer-binding protein homologous protein [CHOP] and cleaved caspase-12) and anti-apoptotic factors (chaperone glucose-regulated protein [GRP] 78 and endoplasmic reticulum-associated protein degradation-associated ubiquitin ligase synovial apoptosis inhibitor 1 [SYVN1]) in the ERS-associated unfolded protein response (UPR) pathway.
RESULTSCompared with age-matched WT mice, 5×FAD mice showed higher cleaved caspase-3, lower neuron-positive staining at the age of 12 months, but earlier cognitive deficit at the age of 7 months (all P < 0.05). Interestingly, for 2-month-old 5×FAD mice, the related proteins involved in the ERS-associated UPR pathway, including CHOP, cleaved caspase-12, GRP 78, and SYVN1, were significantly increased when compared with those in age-matched WT mice (all P < 0.05). Moreover, ERS occurred mainly in neurons, not in astrocytes.
CONCLUSIONSThese findings suggest that compared with those of age-matched WT mice, ERS-associated pro-apoptotic and anti-apoptotic proteins are upregulated in 2-month-old 5×FAD mice, consistent with intracellular Aβ aggregation in neurons.
Alzheimer Disease ; metabolism ; Amyloid beta-Peptides ; metabolism ; Animals ; Apoptosis ; physiology ; Blotting, Western ; Caspase 12 ; metabolism ; Endoplasmic Reticulum Stress ; physiology ; Frontal Lobe ; metabolism ; Heat-Shock Proteins ; metabolism ; Immunohistochemistry ; Mice ; Mice, Transgenic ; Neurons ; metabolism ; Transcription Factor CHOP ; metabolism ; Ubiquitin-Protein Ligases ; metabolism ; Unfolded Protein Response ; physiology
            
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