期刊
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
卷 320, 期 5, 页码 H1813-H1821出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpheart.00999.2020
关键词
ATF6; cardiomyocyte; FAR1; ischemia-reperfusion; peroxisome
资金
- National Heart, Lung, and Blood Institute [R01HL135893, R01 HL141463, R01 HL149931, 1F31HL140850]
- SDSU Heart Institute
- Inamori Foundation
- ARCS Foundation, Inc., San Diego Chapter
By studying neonatal rat ventricular myocytes, it was discovered that the peroxisomal protein FAR1 is upregulated under ER stress and localizes to peroxisomes in cardiac myocytes, reducing myocyte viability during oxidative stress. This implies that plasmalogens may have maladaptive effects on myocyte viability during oxidative stress.
Although peroxisomes have been extensively studied in other cell types, their presence and function have gone virtually unexamined in cardiac myocytes. Here, in neonatal rat ventricular myocytes (NRVM) we showed that several known peroxisomal proteins co-localize to punctate structures with a morphology typical of peroxisomes. Surprisingly, we found that the peroxisomal protein, fatty acyl-CoA reductase 1 (FAR1), was upregulated by pharmacological and pathophysiological ER stress induced by tunicamycin (TM) and simulated ischemia-reperfusion (sI/R), respectively. Moreover, FAR1 induction in NRVM was mediated by the ER stress sensor, activating transcription factor 6 (ATF6). Functionally, FAR1 knockdown reduced myocyte death during oxidative stress induced by either sI/R or hydrogen peroxide (H2O2). Thus, Far1 is an ER stress-inducible gene, which encodes a protein that localizes to peroxisomes of cardiac myocytes, where it reduces myocyte viability during oxidative stress. Since FAR1 is critical for plasmalogen synthesis, these results imply that plasmalogens may exert maladaptive effects on the viability of myocytes exposed to oxidative stress. NEW & NOTEWORTHY The peroxisomal enzyme, FAR1, was shown to be an ER stress- and ATF6-inducible protein that localizes to peroxisomes in cardiac myocytes. FAR1 decreases myocyte viability during oxidative stress.
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