In:
PLOS ONE, Public Library of Science (PLoS), Vol. 15, No. 11 ( 2020-11-30), p. e0242250-
Abstract:
The beta-O-linkage of N-acetylglucosamine (i.e., O-GlcNAc) to proteins is a pro-adaptive response to cellular insults. To this end, increased protein O-GlcNAcylation improves short-term survival of cardiomyocytes subjected to acute injury. This observation has been repeated by multiple groups and in multiple models; however, whether increased protein O-GlcNAcylation plays a beneficial role in more chronic settings remains an open question. Objective Here, we queried whether increasing levels of cardiac protein O-GlcNAcylation would be beneficial during infarct-induced heart failure. Methods and results To achieve increased protein O-GlcNAcylation, we targeted Oga , the gene responsible for removing O-GlcNAc from proteins. Here, we generated mice with cardiomyocyte-restricted, tamoxifen-inducible haploinsufficient Oga gene. In the absence of infarction, we observed a slight reduction in ejection fraction in Oga deficient mice. Overall, Oga reduction had no major impact on ventricular function. In additional cohorts, mice of both sexes and both genotypes were subjected to infarct-induced heart failure and followed for up to four weeks, during which time cardiac function was assessed via echocardiography. Contrary to our prediction, the Oga deficient mice exhibited exacerbated—not improved—cardiac function at one week following infarction. When the observation was extended to 4 wk post-MI, this acute exacerbation was lost. Conclusions The present findings, coupled with our previous work, suggest that altering the ability of cardiomyocytes to either add or remove O-GlcNAc modifications to proteins exacerbates early infarct-induced heart failure. We speculate that more nuanced approaches to regulating O-GlcNAcylation are needed to understand its role—and, in particular, the possibility of cycling, in the pathophysiology of the failing heart.
Type of Medium:
Online Resource
ISSN:
1932-6203
DOI:
10.1371/journal.pone.0242250
DOI:
10.1371/journal.pone.0242250.g001
DOI:
10.1371/journal.pone.0242250.g002
DOI:
10.1371/journal.pone.0242250.g003
DOI:
10.1371/journal.pone.0242250.g004
DOI:
10.1371/journal.pone.0242250.g005
DOI:
10.1371/journal.pone.0242250.t001
DOI:
10.1371/journal.pone.0242250.s001
DOI:
10.1371/journal.pone.0242250.s002
DOI:
10.1371/journal.pone.0242250.s003
DOI:
10.1371/journal.pone.0242250.s004
DOI:
10.1371/journal.pone.0242250.s005
DOI:
10.1371/journal.pone.0242250.s006
DOI:
10.1371/journal.pone.0242250.s007
DOI:
10.1371/journal.pone.0242250.s008
DOI:
10.1371/journal.pone.0242250.s009
DOI:
10.1371/journal.pone.0242250.s010
DOI:
10.1371/journal.pone.0242250.s011
DOI:
10.1371/journal.pone.0242250.s012
DOI:
10.1371/journal.pone.0242250.s013
DOI:
10.1371/journal.pone.0242250.s014
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2020
detail.hit.zdb_id:
2267670-3
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