1.Research progress on the protective effects of heat acclimation on the cardiova-scular system and its molecular mechanisms.
Guo-Yu LI ; Feng GUO ; Zhuo WANG ; Yue HUANG
Acta Physiologica Sinica 2025;77(5):820-838
Heat acclimation provides cardiovascular protection in high-temperature environments through multilevel mechanisms; however, the complete molecular basis of its effects remains unclear. In this paper, we systematically review the effects of heat acclimation on blood volume, vascular function, cardiac structure, energy metabolism, and anti-stress regulation, revealing their potential mechanisms in cardiovascular adaptive protection. We also summarizes the multilevel responses induced by heat stress and heat acclimation, including the modulatory effects of heat acclimation on heat shock proteins (HSPs), hypoxia inducible factor 1 (HIF-1), and apoptotic pathways. Additionally, we highlights the comprehensive protective effects of heat acclimation across various stressors (e.g., hypoxia, heat stress). This review provides a significant physiological basis for cardiovascular disease management and sports medicine, emphasizing the potential application of heat acclimation in response to multiple stressors and supporting its role as an effective tool in cardiovascular health management and stress protection interventions.
Humans
;
Acclimatization/physiology*
;
Hot Temperature
;
Heat-Shock Proteins/metabolism*
;
Animals
;
Heat-Shock Response/physiology*
;
Hypoxia-Inducible Factor 1/metabolism*
;
Apoptosis/physiology*
2.Dexmedetomidine attenuates heat stress-induced oncosis in human skeletal muscle cells by activating the Nrf2/Ho-1 pathway.
Yang LIU ; Yiqing JIA ; Chengcheng LI ; Handing MAO ; Shuyuan LIU ; Yi SHAN
Journal of Southern Medical University 2025;45(3):603-613
OBJECTIVES:
To investigate the protective effects of dexmedetomidine (DEX) against heat stress (HS)-induced oncosis in human skeletal muscle cells (HSKMCs) and its underlying mechanisms.
METHODS:
A HSKMC model of HS-induced oncosis were established by 43 ℃ water bath for 4 h, and the effects of treatments with 30 μmol/L DEX, ML385 (a Nrf2 inhibitor) +DEX, si-Nrf2+HS, and si-Nrf2+DEX prior to modeling on cell viability was assessed using CCK-8 assay. Oncosis characteristics were evaluated using transmission electron microscopy and Annexin V-FITC/PI flow cytometry. The oxidative stress markers (GSH, GSH-Px, MDA, SOD and ROS), mitochondrial membrane potential, energy metabolism, and inflammatory cytokines (TNF-α, IL-6 and IL-1β) in the cells were quantified using standard kits, and the expressions of porimin, caspase-3 and Nrf2 pathway proteins were analyzed using Western blotting and qRT-PCR.
RESULTS:
HS induced typical oncotic features in HSKMCs including organelle swelling and cytoplasmic vacuolization. DEX pretreatment significantly attenuated these changes, reduced Annexin V+/PI+ cell ratio and cellular porimin expression, and lowered the levels of ROS and MDA while restoring GSH and SOD levels. DEX pretreatment also significantly increased the mitochondrial membrane potential and ATP level, upregulated the expressions of Nrf2, p-Nrf2, HO-1 and NQO1, and suppressed the expressions of TNF-α, IL-6 and IL-1β. The protective effects of DEX were obviously attenuated by interventions with ML385 or si-Nrf2.
CONCLUSIONS
DEX mitigates HS-induced HSKMC oncosis by activating the Nrf2/HO-1 pathway to relieve oxidative stress, mitochondrial dysfunction, and inflammatory responses.
Humans
;
Dexmedetomidine/pharmacology*
;
NF-E2-Related Factor 2/metabolism*
;
Oxidative Stress/drug effects*
;
Heat-Shock Response/drug effects*
;
Signal Transduction/drug effects*
;
Membrane Potential, Mitochondrial
;
Muscle, Skeletal/cytology*
;
Heme Oxygenase-1/metabolism*
;
Apoptosis/drug effects*
3.Heat stress affects expression levels of circadian clock gene Bmal1 and cyclins in rat thoracic aortic endothelial cells.
Xiaoyu CHANG ; Hanwen ZHANG ; Hongting CAO ; Ling HOU ; Xin MENG ; Hong TAO ; Yan LUO ; Guanghua LI
Journal of Southern Medical University 2025;45(7):1353-1362
OBJECTIVES:
To investigate the structural changes of rat thoracic aorta and changes in expression levels of Bmal1 and cyclins in thoracic aorta endothelial cells following heat stress.
METHODS:
Twenty male SD rats were randomized equally into control group and heat stress group. After exposure to 32 ℃ for 2 weeks in the latter group, the rats were examined for histopathological changes and Bmal1 expression in the thoracic aorta using HE staining and immunohistochemistry. In the cell experiments, cultured rat thoracic aortic endothelial cells (RTAECs) were incubated at 40 ℃ for 12 h with or without prior transfection with a Bmal1-specific small interfering RNA (si-Bmal1) or a negative sequence. In both rat thoracic aorta and RTAECs, the expressions of Bmal1, the cell cycle proteins CDK1, CDK4, CDK6, and cyclin B1, and apoptosis-related proteins Bax and Bcl-2 were detected using Western blotting. TUNEL staining was used to detect cell apoptosis in rat thoracic aorta, and the changes in cell cycle distribution and apoptosis in RTAECs were analyzed with flow cytometry.
RESULTS:
Compared with the control rats, the rats exposed to heat stress showed significantly increased blood pressures and lowered heart rate with elastic fiber disruption and increased expressions of Bmal1, cyclin B1 and CDK1 in the thoracic aorta (P<0.05). In cultured RTAECs, heat stress caused significant increase of Bmal1, cyclin B1 and CDK1 protein expression levels, which were obviously lowered in cells with prior si-Bmal1 transfection. Bmal1 knockdown also inhibited heat stress-induced increase of apoptosis in RTAECs as evidenced by decreased expression of Bax and increased expression of Bcl-2.
CONCLUSIONS
Heat stress upregulates Bmal1 expression and causes alterations in expressions of cyclins to trigger apoptosis of rat thoracic aorta endothelial cells, which can be partly alleviated by suppressing Bmal1 expression.
Animals
;
ARNTL Transcription Factors/genetics*
;
Male
;
Aorta, Thoracic/metabolism*
;
Rats
;
Rats, Sprague-Dawley
;
Endothelial Cells/metabolism*
;
Apoptosis
;
Cells, Cultured
;
Heat-Shock Response
;
Cyclin B1/metabolism*
;
CDC2 Protein Kinase/metabolism*
;
Cyclins/metabolism*
;
RNA, Small Interfering
;
bcl-2-Associated X Protein/metabolism*
4.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
5.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
6.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
7.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
8.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
9.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
10.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

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