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Uhrf1 regulates H3K9me2 modification of mTOR to inhibit the effect of autophagy in myocardial ischemia-reperfusion injury.
- Source :
-
Aging [Aging (Albany NY)] 2021 Mar 19; Vol. 13 (7), pp. 9704-9718. Date of Electronic Publication: 2021 Mar 19. - Publication Year :
- 2021
-
Abstract
- The regulation of mTOR and the dimethylation of histone H3 on lysine 9 (H3K9me2) H3K9me2 by Uhrf1 and the mechanism of autophagy regulation in myocardial ischemia-reperfusion injury (MIRI) were studied in vivo and in vitro . An in vitro I/R injury model was established using the primary mouse cardiomyocytes treated with H <subscript>2</subscript> O <subscript>2</subscript> . Subsequent analysis by qRT-PCR, western blot, and immunofluorescence indicated that overexpression of Uhrf1 significantly inhibited apoptosis of the H <subscript>2</subscript> O <subscript>2</subscript> -treated cardiomyocytes, reduced expression of apoptosis factors caspase-3 and Bax, and increased expression of apoptosis inhibitory factor Bcl-2. Furthermore, Uhrf1 was found to increase cardiomyocyte proliferation and promote the expression of mTOR, while the four expression peaks of H3K9me2 on the mTOR gene were inhibited by overexpression of Uhrf1. The expression of autophagy factors LC3, Beclin-1, and p-mTOR in Uhrf1-overexpressed cardiomyocytes was dramatically increased, and P62 expression was dramatically decreased. When an H3K9me2 inhibitor was added to the Uhrf1-knockdown cardiomyocytes, the expression of mTOR was increased, the expression of LC3, Beclin-1, and p-mTOR was decreased, and P62 expression was significantly increased. In the present study, Uhrf1 exhibits a protective function in MIRI, reducing the apoptosis of cardiomyocytes while increasing their proliferation and viability.
- Subjects :
- Animals
Apoptosis drug effects
Apoptosis physiology
Autophagy drug effects
Caspase 3 metabolism
Cell Proliferation drug effects
Cell Proliferation physiology
Cell Survival drug effects
Cell Survival physiology
Hydrogen Peroxide pharmacology
Mice
Myocytes, Cardiac drug effects
Signal Transduction drug effects
Signal Transduction physiology
bcl-2-Associated X Protein metabolism
Autophagy physiology
CCAAT-Enhancer-Binding Proteins metabolism
Histones metabolism
Myocardial Reperfusion Injury metabolism
Myocytes, Cardiac metabolism
TOR Serine-Threonine Kinases metabolism
Ubiquitin-Protein Ligases metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1945-4589
- Volume :
- 13
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Aging
- Publication Type :
- Academic Journal
- Accession number :
- 33744855
- Full Text :
- https://doi.org/10.18632/aging.202722