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PARM-1 is an endoplasmic reticulum molecule involved in endoplasmic reticulum stress-induced apoptosis in rat cardiac myocytes.
- Source :
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PloS one [PLoS One] 2010 Mar 18; Vol. 5 (3), pp. e9746. Date of Electronic Publication: 2010 Mar 18. - Publication Year :
- 2010
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Abstract
- To identify novel transmembrane and secretory molecules expressed in cardiac myocytes, signal sequence trap screening was performed in rat neonatal cardiac myocytes. One of the molecules identified was a transmembrane protein, prostatic androgen repressed message-1 (PARM-1). While PARM-1 has been identified as a gene induced in prostate in response to castration, its function is largely unknown. Our expression analysis revealed that PARM-1 was specifically expressed in hearts and skeletal muscles, and in the heart, cardiac myocytes, but not non-myocytes expressed PARM-1. Immunofluorescent staining showed that PARM-1 was predominantly localized in endoplasmic reticulum (ER). In Dahl salt-sensitive rats, high-salt diet resulted in hypertension, cardiac hypertrophy and subsequent heart failure, and significantly stimulated PARM-1 expression in the hearts, with a concomitant increase in ER stress markers such as GRP78 and CHOP. In cultured cardiac myocytes, PARM-1 expression was stimulated by proinflammatory cytokines, but not by hypertrophic stimuli. A marked increase in PARM-1 expression was observed in response to ER stress inducers such as thapsigargin and tunicamycin, which also induced apoptotic cell death. Silencing PARM-1 expression by siRNAs enhanced apoptotic response in cardiac myocytes to ER stresses. PARM-1 silencing also repressed expression of PERK and ATF6, and augmented expression of CHOP without affecting IRE-1 expression and JNK and Caspase-12 activation. Thus, PARM-1 expression is induced by ER stress, which plays a protective role in cardiac myocytes through regulating PERK, ATF6 and CHOP expression. These results suggested that PARM-1 is a novel ER transmembrane molecule involved in cardiac remodeling in hypertensive heart disease.
- Subjects :
- Animals
Cytokines metabolism
Disease Models, Animal
Heart Diseases metabolism
Heat-Shock Proteins metabolism
Hypertension metabolism
RNA, Small Interfering metabolism
Rats
Rats, Inbred Dahl
Rats, Wistar
Transcription Factor CHOP metabolism
Androgen-Binding Protein metabolism
Apoptosis
Endoplasmic Reticulum metabolism
Myocytes, Cardiac cytology
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 5
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 20305782
- Full Text :
- https://doi.org/10.1371/journal.pone.0009746