Bmal1 Regulates the Redox Rhythm of HSPB1, and Homooxidized HSPB1 Attenuates the Oxidative Stress Injury of Cardiomyocytes

Autor: Lianhong Zou, Xingwen Zhang, Yimin Zhu, Xiehong Liu, Weiwei Xiao, Lei Xu, Yu Jiang, Wen Xiao, Yan Cao, Fang Chen
Jazyk: angličtina
Rok vydání: 2021
Předmět:
0301 basic medicine
Male
Aging
medicine.medical_specialty
animal structures
Article Subject
medicine.drug_class
medicine.disease_cause
Biochemistry
Rats
Sprague-Dawley
03 medical and health sciences
Mice
0302 clinical medicine
Internal medicine
Circadian Clocks
Troponin I
Natriuretic peptide
medicine
Animals
Humans
Myocytes
Cardiac
Circadian rhythm
Myocardial infarction
Heat-Shock Proteins
chemistry.chemical_classification
Reactive oxygen species
QH573-671
business.industry
Cardiogenic shock
ARNTL Transcription Factors
Cell Biology
General Medicine
Middle Aged
medicine.disease
Rats
Oxidative Stress
030104 developmental biology
Endocrinology
chemistry
030220 oncology & carcinogenesis
Shock (circulatory)
Female
medicine.symptom
business
Cytology
Oxidation-Reduction
Oxidative stress
Research Article
Molecular Chaperones
Zdroj: Oxidative Medicine and Cellular Longevity
Oxidative Medicine and Cellular Longevity, Vol 2021 (2021)
ISSN: 1942-0994
1942-0900
Popis: Oxidative stress is the main cause of acute myocardial infarction (AMI), which is related to the disorder of the regulation of Bmal1 on the redox state. HSPB1 form homologous-oxidized HSPB1 (homooxidized HSPB1) to resist oxidative damage via S-thiolated modification. However, it is still unclarified whether there is an interaction between the circadian clock and HSPB1 in myocardial injury. A total of 118 AMI patients admitted and treated in our hospital from Sep. 2019 to Sep. 2020 were selected to detect the plasma HSPB1 expression and the redox state. We divided the AMI patients into three subgroups: morning-onset AMI (5 : 00 am to 8 : 00 am; Am-subgroup, n = 38 ), noon-onset AMI (12 : 00 pm to 15 : 00; Pm-subgroup, n = 45 ), and night-onset AMI (20 : 00 pm to 23 : 00 pm; Eve-subgroup, n = 35 ) according to the circadian rhythm of onset. The Am-subgroup had remarkably higher cardiac troponin I (cTnI), creatine kinase MB (CK-MB), and B-type natriuretic peptide (BNP) but lower left ventricular ejection fraction (LVEF) than the Pm-subgroup and Eve-subgroup. Patients complicated with cardiogenic shock were significantly higher in the Am-subgroup than in the other two groups. The homooxidized HSPB1 in plasma markedly decreased in the Am-subgroup. The HSPB1C141S mutant accelerated H9c2 cell apoptosis, increased reactive oxygen species (ROS), and decreased reduced-glutathione (GSH) and the ratio of reduced-GSH and GSSG during oxidative stress. Importantly, we found that the redox state of HSPB1 was consistent with the oscillatory rhythm of Bmal1 expression in normal C57B/L mice. The circadian rhythm disorder contributed to decrease Bmal1 and homooxidized HSPB1 in cardiomyocytes of C57BL/6 mice. In addition, Bmal1 and homooxidized HSPB1 decreased in neonatal rat cardiomyocytes exposed to H2O2. Knockdown of Bmal1 led to significant attenuation in homooxidized HSPB1 expression, whereas overexpression of Bmal1 increased homooxidized HSPB1 expression in response to H2O2. Our findings indicated that the homooxidized HSPB1 reduced probably the AMI patients’ risk of shock and target organ damage, which was associated with Bmal1 regulating the redox state of HSPB1.
Databáze: OpenAIRE
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