PARM-1 Is an Endoplasmic Reticulum Molecule Involved in Endoplasmic Reticulum Stress-Induced Apoptosis in Rat Cardiac Myocyt

Koji Isodono, Tomosaburo Takahashi, Hiroko Imoto, Naohiko Nakanishi, Takehiro Ogata, Satoshi Asada, Atsuo Adachi, Tomomi Ueyama, Hidemasa Oh, Hiroaki Matsubara

Research output: Contribution to journalArticle

42 Citations (Scopus)

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, highsalt 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.

Original languageEnglish
Article numbere9746
JournalPLoS One
Volume5
Issue number3
DOIs
Publication statusPublished - 2010
Externally publishedYes

Fingerprint

Endoplasmic Reticulum Stress
androgens
Endoplasmic Reticulum
endoplasmic reticulum
Androgens
Rats
apoptosis
Apoptosis
Molecules
rats
Cardiac Myocytes
heart
caspase-12
Caspase 12
Inbred Dahl Rats
tunicamycin
Tunicamycin
transmembrane proteins
Thapsigargin
Castration

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Isodono, K., Takahashi, T., Imoto, H., Nakanishi, N., Ogata, T., Asada, S., ... Matsubara, H. (2010). PARM-1 Is an Endoplasmic Reticulum Molecule Involved in Endoplasmic Reticulum Stress-Induced Apoptosis in Rat Cardiac Myocyt. PLoS One, 5(3), [e9746]. https://doi.org/10.1371/journal.pone.0009746

PARM-1 Is an Endoplasmic Reticulum Molecule Involved in Endoplasmic Reticulum Stress-Induced Apoptosis in Rat Cardiac Myocyt. / Isodono, Koji; Takahashi, Tomosaburo; Imoto, Hiroko; Nakanishi, Naohiko; Ogata, Takehiro; Asada, Satoshi; Adachi, Atsuo; Ueyama, Tomomi; Oh, Hidemasa; Matsubara, Hiroaki.

In: PLoS One, Vol. 5, No. 3, e9746, 2010.

Research output: Contribution to journalArticle

Isodono, K, Takahashi, T, Imoto, H, Nakanishi, N, Ogata, T, Asada, S, Adachi, A, Ueyama, T, Oh, H & Matsubara, H 2010, 'PARM-1 Is an Endoplasmic Reticulum Molecule Involved in Endoplasmic Reticulum Stress-Induced Apoptosis in Rat Cardiac Myocyt', PLoS One, vol. 5, no. 3, e9746. https://doi.org/10.1371/journal.pone.0009746
Isodono, Koji ; Takahashi, Tomosaburo ; Imoto, Hiroko ; Nakanishi, Naohiko ; Ogata, Takehiro ; Asada, Satoshi ; Adachi, Atsuo ; Ueyama, Tomomi ; Oh, Hidemasa ; Matsubara, Hiroaki. / PARM-1 Is an Endoplasmic Reticulum Molecule Involved in Endoplasmic Reticulum Stress-Induced Apoptosis in Rat Cardiac Myocyt. In: PLoS One. 2010 ; Vol. 5, No. 3.
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