FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W1609254757> ?p ?o ?g. }

• W1609254757 abstract "In diabetes mellitus the morbidity and mortality of cardiovascular disease is increased and represents an important independent mechanism by which heart disease is exacerbated. The pathogenesis of diabetic cardiomyopathy involves the enhanced activation of PPAR transcription factors, including PPARα, and to a lesser degree PPARβ and PPARγ1. How these transcription factors are regulated in the heart is largely unknown. Recent studies have described post-translational ubiquitination of PPARs as ways in which PPAR activity is inhibited in cancer. However, specific mechanisms in the heart have not previously been described. Recent studies have implicated the muscle-specific ubiquitin ligase muscle ring finger-2 (MuRF2) in inhibiting the nuclear transcription factor SRF. Initial studies of MuRF2−/− hearts revealed enhanced PPAR activity, leading to the hypothesis that MuRF2 regulates PPAR activity by post-translational ubiquitination. MuRF2−/− mice were challenged with a 26-week 60% fat diet designed to simulate obesity-mediated insulin resistance and diabetic cardiomyopathy. Mice were followed by conscious echocardiography, blood glucose, tissue triglyceride, glycogen levels, immunoblot analysis of intracellular signaling, heart and skeletal muscle morphometrics, and PPARα, PPARβ, and PPARγ1-regulated mRNA expression. MuRF2 protein levels increase ~20% during the development of diabetic cardiomyopathy induced by high fat diet. Compared to littermate wildtype hearts, MuRF2−/− hearts exhibit an exaggerated diabetic cardiomyopathy, characterized by an early onset systolic dysfunction, larger left ventricular mass, and higher heart weight. MuRF2−/− hearts had significantly increased PPARα- and PPARγ1-regulated gene expression by RT-qPCR, consistent with MuRF2’s regulation of these transcription factors in vivo. Mechanistically, MuRF2 mono-ubiquitinated PPARα and PPARγ1 in vitro, consistent with its non-degradatory role in diabetic cardiomyopathy. However, increasing MuRF2:PPARγ1 (>5:1) beyond physiological levels drove poly-ubiquitin-mediated degradation of PPARγ1 in vitro, indicating large MuRF2 increases may lead to PPAR degradation if found in other disease states. Mutations in MuRF2 have been described to contribute to the severity of familial hypertrophic cardiomyopathy. The present study suggests that the lack of MuRF2, as found in these patients, can result in an exaggerated diabetic cardiomyopathy. These studies also identify MuRF2 as the first ubiquitin ligase to regulate cardiac PPARα and PPARγ1 activities in vivo via post-translational modification without degradation." @default.
• W1609254757 created "2016-06-24" @default.
• W1609254757 creator A5005086170 @default.
• W1609254757 creator A5006213707 @default.
• W1609254757 creator A5010825727 @default.
• W1609254757 creator A5015135988 @default.
• W1609254757 creator A5017516899 @default.
• W1609254757 creator A5017540265 @default.
• W1609254757 creator A5019380061 @default.
• W1609254757 creator A5028997082 @default.
• W1609254757 creator A5029499930 @default.
• W1609254757 creator A5031084037 @default.
• W1609254757 creator A5040595417 @default.
• W1609254757 creator A5047669723 @default.
• W1609254757 creator A5052353077 @default.
• W1609254757 creator A5062992566 @default.
• W1609254757 creator A5069025186 @default.
• W1609254757 creator A5076537324 @default.
• W1609254757 creator A5081821816 @default.
• W1609254757 date "2015-08-05" @default.
• W1609254757 modified "2023-10-17" @default.
• W1609254757 title "MuRF2 regulates PPARγ1 activity to protect against diabetic cardiomyopathy and enhance weight gain induced by a high fat diet" @default.
• W1609254757 cites W1566724399 @default.
• W1609254757 cites W1567411317 @default.
• W1609254757 cites W1574112426 @default.
• W1609254757 cites W1597941165 @default.
• W1609254757 cites W1607586648 @default.
• W1609254757 cites W1672123070 @default.
• W1609254757 cites W1916657993 @default.
• W1609254757 cites W1967400215 @default.
• W1609254757 cites W1968305991 @default.
• W1609254757 cites W1975796727 @default.
• W1609254757 cites W1978781045 @default.
• W1609254757 cites W1979595579 @default.
• W1609254757 cites W1979976015 @default.
• W1609254757 cites W1982185581 @default.
• W1609254757 cites W1982380248 @default.
• W1609254757 cites W1984706808 @default.
• W1609254757 cites W1985629225 @default.
• W1609254757 cites W1987003603 @default.
• W1609254757 cites W1987320803 @default.
• W1609254757 cites W1987713254 @default.
• W1609254757 cites W1990349157 @default.
• W1609254757 cites W1991430539 @default.
• W1609254757 cites W1993235298 @default.
• W1609254757 cites W1995868373 @default.
• W1609254757 cites W1996816319 @default.
• W1609254757 cites W1998290880 @default.
• W1609254757 cites W2000379370 @default.
• W1609254757 cites W2000773294 @default.
• W1609254757 cites W2001330437 @default.
• W1609254757 cites W2001512276 @default.
• W1609254757 cites W2002568383 @default.
• W1609254757 cites W2004324027 @default.
• W1609254757 cites W2006051234 @default.
• W1609254757 cites W2010195338 @default.
• W1609254757 cites W2012937324 @default.
• W1609254757 cites W2013339424 @default.
• W1609254757 cites W2015774467 @default.
• W1609254757 cites W2015777977 @default.
• W1609254757 cites W2019402080 @default.
• W1609254757 cites W2020170906 @default.
• W1609254757 cites W2021176126 @default.
• W1609254757 cites W2021469711 @default.
• W1609254757 cites W2021871393 @default.
• W1609254757 cites W2022174018 @default.
• W1609254757 cites W2024173579 @default.
• W1609254757 cites W2024942196 @default.
• W1609254757 cites W2028825337 @default.
• W1609254757 cites W2031606593 @default.
• W1609254757 cites W2033307728 @default.
• W1609254757 cites W2033789572 @default.
• W1609254757 cites W2034024903 @default.
• W1609254757 cites W2035050651 @default.
• W1609254757 cites W2039457074 @default.
• W1609254757 cites W2040065416 @default.
• W1609254757 cites W2040978941 @default.
• W1609254757 cites W2044741742 @default.
• W1609254757 cites W2048057768 @default.
• W1609254757 cites W2048114546 @default.
• W1609254757 cites W2050745715 @default.
• W1609254757 cites W2051409222 @default.
• W1609254757 cites W2056487036 @default.
• W1609254757 cites W2058518321 @default.
• W1609254757 cites W2059081636 @default.
• W1609254757 cites W2061929833 @default.
• W1609254757 cites W2063376078 @default.
• W1609254757 cites W2068677664 @default.
• W1609254757 cites W2072366020 @default.
• W1609254757 cites W2074332237 @default.
• W1609254757 cites W2075728010 @default.
• W1609254757 cites W2079386976 @default.
• W1609254757 cites W2081356823 @default.
• W1609254757 cites W2082532918 @default.
• W1609254757 cites W2084634578 @default.
• W1609254757 cites W2088403696 @default.
• W1609254757 cites W2091003171 @default.
• W1609254757 cites W2092363626 @default.
• W1609254757 cites W2092862331 @default.
• W1609254757 cites W2096772012 @default.

• next