Testosterone antagonizes paraquat-induced cardiomyocyte senescence via the mIGF-1/SIRT1 signaling pathway
Braz. j. med. biol. res
; 53(10): e9849, 2020. tab, graf
Article
em En
| LILACS, ColecionaSUS
| ID: biblio-1132481
Biblioteca responsável:
BR1.1
ABSTRACT
Testosterone has been demonstrated to antagonize doxorubicin-induced cardiomyocyte senescence. However, whether testosterone prevents the paraquat-induced cardiomyocyte senescence is largely unknown. The detection of SA-β-gal activity was performed using senescence β-gal staining kit and the reactive oxygen species levels were determined by reactive oxygen species assay kit. The plasmids for insulin-like growth factor 1 shRNA (sh-mIGF-1), sirtuin-1 shRNA (sh-SIRT1), scramble shRNA (sh-NC), overexpressing mIGF-1 (mIGF-1), overexpressing SIRT1 (SIRT1), and negative controls (NC) were obtained for this study. The expression of target genes was detected using quantitative real-time PCR, immunolabeling, and western blot. We found that testosterone significantly delayed the paraquat-induced HL-1 cardiomyocyte senescence as evidenced by decreasing senescence-associated β-galactosidase activity and reactive oxygen species generation, which were accompanied by the up-regulated expression of mIGF-1 and SIRT1. RNA interference to reduce mIGF-1 and SIRT1 expression showed that testosterone prevented paraquat-induced HL-1 senescence via the mIGF-1/SIRT1 signaling pathway. Furthermore, myocardial contraction was evaluated by expression of genes of the contractile proteins/enzymes, such as α-myosin heavy chain 6 (MHC6), α-myosin heavy chain 7 (MHC7), α-skeletal actin (ACTA-1), and sarco/endoplasmic reticulum calcium ATPase-2 (SERCA2). Testosterone adjusted the above four gene expressions and the adjustment was blocked by mIGF-1 or SIRT1 inhibition. Our findings suggested that the mIGF-1/SIRT1 signaling pathway mediated the protective function of testosterone against the HL-1 cardiomyocyte senescence by paraquat, which provided new clues for the mechanisms underlying the anti-aging role of testosterone in cardiomyocytes.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
LILACS
/
ColecionaSUS
Assunto principal:
Paraquat
/
Testosterona
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Miócitos Cardíacos
/
Sirtuína 1
Idioma:
En
Revista:
Braz. j. med. biol. res
Assunto da revista:
BIOLOGIA
/
MEDICINA
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
China
País de publicação:
Brasil