Dexmedetomidine reversed hypoxia/reoxygenation injury-induced oxidative stress and endoplasmic reticulum stress-dependent apoptosis of cardiomyocytes via SIRT1/CHOP signaling pathway.
Mol Cell Biochem
; 476(7): 2803-2812, 2021 Jul.
Article
em En
| MEDLINE
| ID: mdl-33725228
ABSTRACT
We aimed to investigate the protective role and mechanism of dexmedetomidine (DEX) on H9c2 cardiomyocytes after hypoxia/reoxygenation (H/R) injury. Six experimental groups were designed as follows normal control group (group C), H/R group, H/R + DEX group, H/R + gastrodin group, H/R + Ex527 (SIRT1 inhibitor) group, and H/R + DEX + Ex527 group. Lactate dehydrogenase (LDH) activity and the levels of oxidative stress-related enzymes such as malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT) and glutathione (GSH) were measured using corresponding commercial kits. Cell counting kit (CCK)-8 assay was used to detect cell survival rate while flow cytometry and caspase 3/7 activity were used to determine cell apoptosis, respectively. Western blot was used to detect the expression of silent information regulator 1 (SIRT1), C/EBP homologous protein (CHOP), cleaved-caspase-12/3 and pro-caspase-12/3 in each group. From our findings, when compared with H/R, H/R + Ex527 and H/R + DEX + Ex527 groups, DEX pretreatment of cells in H/R + DEX group significantly increased cell survival rate, and simultaneously reduced LDH activity, oxidative stress and the apoptosis rate of H9c2 cells with H/R injury. Moreover, DEX up-regulated SIRT1 expression level and down-regulated the levels of endoplasmic reticulum (ER) stress-related markers such as CHOP, cleaved-caspase-12 and cleaved-caspase-3, respectively. Ex527 could completely block DEX-induced upregulated expression of SIRT1, and partially blocked the DEX-induced downregulated expression levels of CHOP, cleaved-caspase-12 and cleaved-caspase-3. These results proved that DEX reversed H/R injury-induced oxidative stress and ER stress-dependent apoptosis of cardiomyocytes via SIRT1/CHOP signaling pathway.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Traumatismo por Reperfusão Miocárdica
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Transdução de Sinais
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Apoptose
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Estresse Oxidativo
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Dexmedetomidina
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Miócitos Cardíacos
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Fator de Transcrição CHOP
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Sirtuína 1
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Estresse do Retículo Endoplasmático
Limite:
Animals
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article