Article ; Online: BAG3 expression and sarcomere localization in the human heart are linked to HSF-1 and are differentially affected by sex and disease.
American journal of physiology. Heart and circulatory physiology
2021 Volume 320, Issue 6, Page(s) H2339–H2350
Abstract: Mutations to the sarcomere-localized cochaperone protein Bcl2-associated athanogene 3 (BAG3) are associated with dilated cardiomyopathy (DCM) and display greater penetrance in male patients. Decreased protein expression of BAG3 is also associated with ... ...
| Abstract | Mutations to the sarcomere-localized cochaperone protein Bcl2-associated athanogene 3 (BAG3) are associated with dilated cardiomyopathy (DCM) and display greater penetrance in male patients. Decreased protein expression of BAG3 is also associated with nongenetic heart failure; however, the factors regulating cardiac BAG3 expression are unknown. Using left ventricular (LV) tissue from nonfailing and DCM human samples, we found that whole LV BAG3 expression was not significantly impacted by DCM or sex; however, myofilament localized BAG3 was significantly decreased in males with DCM. Females with DCM displayed no changes in BAG3 compared with nonfailing. This sex difference appears to be estrogen independent, as estrogen treatment in ovariectomized female rats had no impact on BAG3 expression. BAG3 gene expression in noncardiac cells is primarily regulated by the heat shock transcription factor-1 (HSF-1). We show whole LV HSF-1 expression and nuclear localized/active HSF-1 each displayed a striking positive correlation with whole LV BAG3 expression. We further found that HSF-1 localizes to the sarcomere |
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| MeSH term(s) | Adaptor Proteins, Signal Transducing/metabolism ; Adult ; Aged ; Animals ; Apoptosis Regulatory Proteins/metabolism ; Cardiomyopathy, Dilated/metabolism ; Female ; Gene Expression ; Heart Ventricles/metabolism ; Heat Shock Transcription Factors/metabolism ; Humans ; Male ; Microscopy, Fluorescence ; Middle Aged ; Myocardium/metabolism ; Myocardium/pathology ; Myocytes, Cardiac/metabolism ; Myocytes, Cardiac/pathology ; Myofibrils/metabolism ; Ovariectomy ; Rats ; Sarcomeres/metabolism ; Sarcomeres/pathology ; Sex Factors |
| Chemical Substances | Adaptor Proteins, Signal Transducing ; Apoptosis Regulatory Proteins ; BAG3 protein, human ; BAG3 protein, rat ; HSF1 protein, human ; Heat Shock Transcription Factors ; Hsf1 protein, rat |
| Language | English |
| Publishing date | 2021-05-14 |
| Publishing country | United States |
| Document type | Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't |
| ZDB-ID | 603838-4 |
| ISSN | 1522-1539 ; 0363-6135 |
| ISSN (online) | 1522-1539 |
| ISSN | 0363-6135 |
| DOI | 10.1152/ajpheart.00419.2020 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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