1.Excess Oxygen Supply for Different Time Periods Affect Energy Metabolism in Rat Alveolar Epithelial Type Ⅱ Cells.
Rong-Rong HUANG ; Shan-Shan QU ; Hong GUO ; Su-Heng CHEN ; Chuan-Qi YANG ; Jun-Mei ZHANG ; Yu-Lan LI
Acta Academiae Medicinae Sinicae 2023;45(1):9-15
Objective To observe the effect of excess oxygen supply for different time periods on the mitochondrial energy metabolism in alveolar epithelial type Ⅱ cells. Methods Rat RLE-6TN cells were assigned into a control group (21% O2 for 4 h) and excess oxygen supply groups (95% O2 for 1,2,3,and 4 h,res-pectively).The content of adenosine triphosphate (ATP),the activity of mitochondrial respiratory chain complex V,and the mitochondrial membrane potential were determined by luciferase assay,micro-assay,and fluorescent probe JC-1,respectively.Real-time fluorescence quantitative PCR was employed to determine the mRNA levels of NADH dehydrogenase subunit 1 (ND1),cytochrome b (Cytb),cytochrome C oxidase subunit I (COXI),and adenosine triphosphatase 6 (ATPase6) in the core subunits of mitochondrial respiratory chain complexes Ⅰ,Ⅲ,Ⅳ,and Ⅴ,respectively. Results Compared with the control group,excess oxygen supply for 1,2,3,and 4 h down-regulated the mRNA levels of ND1 (q=24.800,P<0.001;q=13.650,P<0.001;q=9.869,P<0.001;q=20.700,P<0.001),COXI (q=16.750,P<0.001;q=10.120,P<0.001;q=8.476,P<0.001;q=14.060,P<0.001),and ATPase6 (q=22.770,P<0.001;q=15.540,P<0.001;q=12.870,P<0.001;q=18.160,P<0.001).Moreover,excess oxygen supply for 1 h and 4 h decreased the ATPase activity (q=9.435,P<0.001;q=11.230,P<0.001) and ATP content (q=5.615,P=0.007;q=5.029,P=0.005).The excess oxygen supply for 2 h and 3 h did not cause significant changes in ATPase activity (q=0.156,P=0.914;q=3.197,P=0.116) and ATP content (q=0.859,P=0.557;q=1.273,P=0.652).There was no significant difference in mitochondrial membrane potential among the groups (F=0.303,P=0.869). Conclusion Short-term excess oxygen supply down-regulates the expression of the core subunits of mitochondrial respiratory chain complexes and reduces the activity of ATPase,leading to the energy metabolism disorder of alveolar epithelial type Ⅱ cells.
Animals
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Rats
;
Energy Metabolism
;
Adenosine Triphosphate
;
Adenosine Triphosphatases
;
RNA, Messenger
;
Oxygen
2.Neuroglobin Facilitates Neuronal Oxygenation through Tropic Migration under Hypoxia or Anemia in Rat: How Does the Brain Breathe?
Chun-Yang LI ; Hai-Feng JIANG ; Li LI ; Xiao-Jing LAI ; Qian-Rong LIU ; Shang-Bin YU ; Cheng-La YI ; Xiao-Qian CHEN
Neuroscience Bulletin 2023;39(10):1481-1496
The discovery of neuroglobin (Ngb), a brain- or neuron-specific member of the hemoglobin family, has revolutionized our understanding of brain oxygen metabolism. Currently, how Ngb plays such a role remains far from clear. Here, we report a novel mechanism by which Ngb might facilitate neuronal oxygenation upon hypoxia or anemia. We found that Ngb was present in, co-localized to, and co-migrated with mitochondria in the cell body and neurites of neurons. Hypoxia induced a sudden and prominent migration of Ngb towards the cytoplasmic membrane (CM) or cell surface in living neurons, and this was accompanied by the mitochondria. In vivo, hypotonic and anemic hypoxia induced a reversible Ngb migration toward the CM in cerebral cortical neurons in rat brains but did not alter the expression level of Ngb or its cytoplasm/mitochondria ratio. Knock-down of Ngb by RNA interference significantly diminished respiratory succinate dehydrogenase (SDH) and ATPase activity in neuronal N2a cells. Over-expression of Ngb enhanced SDH activity in N2a cells upon hypoxia. Mutation of Ngb at its oxygen-binding site (His64) significantly increased SDH activity and reduced ATPase activity in N2a cells. Taken together, Ngb was physically and functionally linked to mitochondria. In response to an insufficient oxygen supply, Ngb migrated towards the source of oxygen to facilitate neuronal oxygenation. This novel mechanism of neuronal respiration provides new insights into the understanding and treatment of neurological diseases such as stroke and Alzheimer's disease and diseases that cause hypoxia in the brain such as anemia.
Rats
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Animals
;
Neuroglobin/metabolism*
;
Globins/metabolism*
;
Nerve Tissue Proteins/metabolism*
;
Neurons/metabolism*
;
Hypoxia/metabolism*
;
Brain/metabolism*
;
Oxygen
;
Anemia/metabolism*
;
Adenosine Triphosphatases/metabolism*
4.SMARCA2 deficiency in NSCLC: a clinicopathologic and immunohistochemical analysis of a large series from a single institution.
Shanshan SUN ; Qiujing LI ; Zhenkun ZHANG ; Sili XIONG ; Yujie ZHANG ; Qian LIU ; Zhe LI ; Fujun YANG ; Shukun ZHANG
Environmental Health and Preventive Medicine 2022;27(0):3-3
BACKGROUND:
SMARCA2 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator of Chromatin, Subfamily A, Member 2) is an important ATPase catalytic subunit in the switch-sucrose nonfermenting (SWI/SNF) complex. However, its relationship with the pathological features of NSCLC and its prognosis remain unclear.
METHODS:
We retrospectively reviewed 2390 patients with surgically resected NSCLC, constructed tissue microarrays (TMAs) and performed immunohistochemical assays. We analyzed the correlation of SAMRCA2 with clinicopathological features and evaluated its prognostic value.
RESULTS:
Among 2390 NSCLC cases, the negative expression ratios of SAMRCA2, SMARCA4, ARID1A, ARID1B and INI1 were 9.3%, 1.8%, 1.2%, 0.4% and 0%, respectively. In NSCLC, male sex, T3 and T4 stage, moderate and poor differentiation, tumor ≥ 2 cm, Ki67 ≥ 15%, SOX-2 negative expression, middle lobe lesion and adenocarcinoma were relative risk factors affecting SMARCA2-negative expression. In lung adenocarcinomas, high-grade nuclei, histological morphology of acinar and papillary, solid and micropapillary and TTF-1-negative expression were relative risk factors affecting SMARCA2-negative expression. Kaplan-Meier survival analysis showed that the OS was shorter in the SMARCA2-negative group. Multivariate survival analysis revealed that SMARCA2-negative expression was an independent factor correlated with a poor prognosis in NSCLC.
CONCLUSION
In conclusion, SMARCA2-negative expression is an independent predictor of a poor outcome of NSCLC and is a potential target for NSCLC treatment.
Adenosine Triphosphatases/metabolism*
;
Carcinoma, Non-Small-Cell Lung/genetics*
;
Humans
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Male
;
Retrospective Studies
;
Transcription Factors/genetics*
5.Advances in plant heavy metal transporter P1B-ATPases.
Penghu AN ; Duomin ZHANG ; Zifang ZHOU ; Dan HAN ; Zicheng XU ; Wuxing HUANG
Chinese Journal of Biotechnology 2021;37(9):3020-3030
P1B-ATPases are a group of proteins that can transport heavy metal ions across membranes by hydrolyzing ATP and they are a subclass of the P-type ATPase family. It was found that P1B-ATPases are mainly responsible for the active transport of heavy metal ions in plants and play an important role in the regulation of heavy metal homeostasis in plants. In this paper, we dissusses the mechanism of P1B-ATPases from the structure and classification of P1B-ATPases, and review the current research progress in the function of P1B-ATPases, in order to provide reference for future research and application of P1B-ATPases in improving crop quality and ecological environment management.
Adenosine Triphosphatases/metabolism*
;
Biological Transport
;
Metals, Heavy
;
Plants/enzymology*
6.Involvement of mitochondrial dysfunction in hepatotoxicity induced by Ageratina adenophora in mice.
Wei SUN ; Chao-Rong ZENG ; Dong YUE ; Yan-Chun HU
Journal of Zhejiang University. Science. B 2019;20(8):693-698
Ageratina adenophora is a noxious plant and it is known to cause acute asthma, diarrhea, depilation, and even death in livestock (Zhu et al., 2007; Wang et al., 2017). A. adenophora grows near roadsides and degraded land worldwide (He et al., 2015b). In the areas where it grows, A. adenophora is an invasive species that inhibits the growth of local plants and causes poisoning in animals that come in contact with it (Nie et al., 2012). In China, these plants can be found in Yunnan, Sichuan, Guizhou, Chongqing, and other southwestern areas (He et al., 2015a) and they have become a dominant species in these local regions. It threatens the native biodiversity and ecosystem in the invaded areas and causes serious economic losses (Wang et al., 2017). It has been reported that A. adenophora can grow in the northeast direction at a speed of 20 km per year in China (Guo et al., 2009). Because of the damage caused by A. adenophora, it ranks among the earliest alien invasive plant species in China (Wang et al., 2017).
Adenosine Triphosphatases/metabolism*
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Ageratina/toxicity*
;
Animals
;
Biodiversity
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Chemical and Drug Induced Liver Injury/pathology*
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China
;
DNA, Mitochondrial/genetics*
;
Ecosystem
;
Introduced Species
;
Liver/drug effects*
;
Mice
;
Microscopy, Electron, Transmission
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Mitochondria, Liver/pathology*
;
Plant Extracts/toxicity*
7.Effects of soybean isoflavones on the energy metabolism of swimming mice.
Bing-Nan DENG ; Jing-Ran SUN ; Hong JIN ; Hong-Jing NIE ; Rui-Feng DUAN ; Lie LIU ; Zhi-Xian GAO ; Zhao-Li CHEN
Chinese Journal of Applied Physiology 2018;34(1):39-42
OBJECTIVE:
To establish an animal model for loaded swimming, so as to investigate the energy metabolism effects of soybean isoflavones (SI) on swimming mice.
METHODS:
Thirty male Kunming mice were randomly divided into three groups:normal control, swimming group, and swimming+SI group. The normal control group mice were fed a basic AIN-93M diet, the SI groups were supplied with soybean isoflavones(4 g/kg).Two weeks later, the mice were forced to swim for an hour,and then all the mice were killed, the samples of blood, liver and muscles of hind were collected.The serum contents of lactic acid(Lac), the activities of lactic dehydrogenase (LDH), succinate dehydrogenase (SDH), creatine kinase (CK) and ATPase were measured.
RESULTS:
Compared with normal control,the serum content of Lac was significantly improved in the group of the swimming control and SI(<0.05),the activity of LDH in the serum was obviously improved in the group of the swimming control and SI, and the activity of CK and SDH were both significantly improved in the group of the swimming control and SI except the activity of SDH in the liver of the group SI; compared with the swimming control,the serum contents of Lac,the activities of LDH, ATPase, SDH, CK were obviously improved(<0.05).
CONCLUSIONS
Soybean isoflavones can improve the energy metabolism,antioxidant capacity of the swimming mice.
Adenosine Triphosphatases
;
blood
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Animals
;
Creatine Kinase
;
blood
;
Energy Metabolism
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Isoflavones
;
pharmacology
;
L-Lactate Dehydrogenase
;
blood
;
Lactic Acid
;
blood
;
Male
;
Mice
;
Random Allocation
;
Soybeans
;
chemistry
;
Succinate Dehydrogenase
;
blood
;
Swimming
8.Effect of baicalin on ATPase and LDH and its regulatory effect on the AC/cAMP/PKA signaling pathway in rats with attention deficit hyperactivity disorder.
Rong-Yi ZHOU ; Jiao-Jiao WANG ; Yue YOU ; Ji-Chao SUN ; Yu-Chen SONG ; Hai-Xia YUAN ; Xin-Min HAN
Chinese Journal of Contemporary Pediatrics 2017;19(5):576-582
OBJECTIVETo study the effect of baicalin on synaptosomal adenosine triphosphatase (ATPase) and lactate dehydrogenase (LDH) and its regulatory effect on the adenylate cyclase (AC)/cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) signaling pathway in rats with attention deficit hyperactivity disorder (ADHD).
METHODSA total of 40 SHR rats were randomly divided into five groups: ADHD model, methylphenidate hydrochloride treatment (0.07 mg/mL), and low-dose (3.33 mg/mL), medium-dose (6.67 mg/mL), and high-dose (10 mg/mL) baicalin treatment (n=8 each). Eight WKY rats were selected as normal control group. Percoll density gradient centrifugation was used to prepare brain synaptosomes and an electron microscope was used to observe their structure. Colorimetry was used to measure the activities of ATPase and LDH in synaptosomes. ELISA was used to measure the content of AC, cAMP, and PKA.
RESULTSCompared with the normal control group, the ADHD model group had a significant reduction in the ATPase activity, a significant increase in the LDH activity, and significant reductions in the content of AC, cAMP, and PKA (P<0.05). Compared with the ADHD model group, the methylphenidate hydrochloride group and the medium- and high-dose baicalin groups had a significant increase in the ATPase activity (P<0.05), a significant reduction in the LDH activity (P<0.05), and significant increases in the content of AC, cAMP, and PKA (P<0.05). Compared with the methylphenidate hydrochloride group, the high-dose baicalin group had significantly greater changes in these indices (P<0.05). Compared with the low-dose baicalin group, the high-dose baicalin group had a significant increase in the ATPase activity (P<0.05); the medium- and high-dose baicalin groups had a significant reduction in the LDH activity (P<0.05) and significant increases in the content of AC, cAMP, and PKA (P<0.05). Compared with the medium-dose baicalin group, the high-dose baicalin group had a significant increase in the ATPase activity (P<0.05).
CONCLUSIONSBoth methylphenidate hydrochloride and baicalin can improve synaptosomal ATPase and LDH activities in rats with ADHD. The effect of baicalin is dose-dependent, and high-dose baicalin has a significantly greater effect than methylphenidate hydrochloride. Baicalin exerts its therapeutic effect possibly by upregulating the AC/cAMP/PKA signaling pathway.
Adenosine Triphosphatases ; metabolism ; Adenylyl Cyclases ; physiology ; Animals ; Attention Deficit Disorder with Hyperactivity ; drug therapy ; physiopathology ; Cyclic AMP ; physiology ; Cyclic AMP-Dependent Protein Kinases ; physiology ; Flavonoids ; pharmacology ; therapeutic use ; L-Lactate Dehydrogenase ; metabolism ; Rats ; Rats, Inbred SHR ; Rats, Inbred WKY ; Signal Transduction ; drug effects ; Synaptosomes ; chemistry ; ultrastructure
9.Dynamic changes of aciduric virulence factor membrane-bound proton-translocating ATPase of Streptococcus mutans in the development of dental caries.
West China Journal of Stomatology 2016;34(2):200-204
OBJECTIVETo observe the dynamic changes of membrane-bound proton-translocating ATPase (F-ATPase) in the development of dental caries, the expression of Streptococcus mutans F-ATPase under different pH concentrations and during the development of dental caries is analyzed.
METHODSStreptococcus mutans cultured under different pH (pH4.0-7.0) concentrations and containing 5% glucose and no glucose containing BHI were collected. RNA was extracted. Subsequently, F-ATPase gene was detected using real-time polymerase chain reaction. Male Wistar rats were divided randomly into caries group and control group. The rats in the caries group were fed caries feed and 5% glucose water, whereas those of control group were fed normal feed. Total RNA was extracted from plaque samples, which were collected from rats' oral cavity every two weeks. F-ATPase gene was detected by real-time PCR. In the 11th week, the upper and lower jaw bone specimens of rats were taken, and molar caries damage assessed.
RESULTSThe expression of F-ATPase in the caries group was higher than that in the control group (P<0.05). In addition, the gene was expressed highest in pH5.0 and the lowest in pH4.0 (P<0.05). 2) The expression of F-ATPase progressively increased during the caries development in both groups; expression in the caries group was higher than that in control group (P<0.05).
CONCLUSIONAcid-resisting viru-lence factor F-ATPase is related closely with the incidence and development of dental caries.
Adenosine Triphosphatases ; metabolism ; Animals ; Dental Caries ; metabolism ; microbiology ; Dental Plaque ; microbiology ; Male ; Protons ; Random Allocation ; Rats ; Rats, Wistar ; Real-Time Polymerase Chain Reaction ; Streptococcus mutans ; drug effects ; genetics ; Virulence Factors
10.DNA mismatch repair-related protein loss as a prognostic factor in endometrial cancers.
Masafumi KATO ; Masashi TAKANO ; Morikazu MIYAMOTO ; Naoki SASAKI ; Tomoko GOTO ; Hitoshi TSUDA ; Kenichi FURUYA
Journal of Gynecologic Oncology 2015;26(1):40-45
OBJECTIVE: Recent investigations have revealed DNA mismatch repair (MMR) gene mutations are closely related with carcinogenesis of endometrial cancer; however the impact of MMR protein expression on prognosis is not determined. Correlations between MMR-related protein expression and clinicopathological factors of endometrial cancers are analyzed in the present study. METHODS: A total of 191 endometrial cancer tissues treated between 1990 and 2007 in our hospital were enrolled. Immunoreactions for MSH2, MLH1, MSH6, and PMS2 on tissue microarray specimens and clinicopathological features were analyzed retrospectively. RESULTS: Seventy-six cases (40%) had at least one immunohistochemical alteration in MMR proteins (MMR-deficient group). There were statistically significant differences of histology, International Federation of Gynecology and Obstetrics (FIGO) stage, and histological grade between MMR-deficient group and the other cases (MMR-retained group). Response rate of first-line chemotherapy in evaluable cases was slightly higher in MMR-deficient cases (67% vs. 44%, p=0.34). MMR-deficient cases had significantly better progression-free and overall survival (OS) compared with MMR-retained cases. Multivariate analysis revealed MMR status was an independent prognostic factor for OS in endometrial cancers. CONCLUSION: MMR-related proteins expression was identified as an independent prognostic factor for OS, suggesting that MMR was a key biomarker for further investigations of endometrial cancers.
Adaptor Proteins, Signal Transducing/deficiency/metabolism
;
Adenosine Triphosphatases/deficiency/metabolism
;
Adult
;
Aged
;
Aged, 80 and over
;
Chemotherapy, Adjuvant
;
*DNA Mismatch Repair
;
DNA Repair Enzymes/deficiency/*metabolism
;
DNA-Binding Proteins/deficiency/*metabolism
;
Endometrial Neoplasms/*diagnosis/drug therapy/genetics/pathology
;
Female
;
Humans
;
Kaplan-Meier Estimate
;
Middle Aged
;
MutS Homolog 2 Protein/deficiency/metabolism
;
Neoplasm Proteins/deficiency/metabolism
;
Nuclear Proteins/deficiency/metabolism
;
Prognosis
;
Retrospective Studies
;
Tumor Markers, Biological/*metabolism

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