title: Infarct-induced steroidogenic acute regulatory protein: a survival role in cardiac fibroblasts.
abstract: Steroidogenic acute regulatory protein (StAR) is indispensable for steroid hormone synthesis in the adrenal cortex and the gonadal tissues. This study reveals that StAR is also expressed at high levels in nonsteroidogenic cardiac fibroblasts confined to the left ventricle of mouse heart examined 3 days after permanent ligation of the left anterior descending coronary artery. Unlike StAR, CYP11A1 and 3β-hydroxysteroid dehydrogenase proteins were not observed in the postinfarction heart, suggesting an apparent lack of de novo cardiac steroidogenesis. Work with primary cultures of rat heart cells revealed that StAR is induced in fibroblasts responding to proapoptotic treatments with hydrogen peroxide or the kinase inhibitor staurosporine (STS). Such induction of StAR in culture was noted before spontaneous differentiation of the fibroblasts to myofibroblasts. STS induction of StAR in the cardiac fibroblasts conferred a marked resistance to apoptotic cell death. Consistent with that finding, down-regulation of StAR by RNA interference proportionally increased the number of STS-treated apoptotic cells. StAR down-regulation also resulted in a marked increase of BAX activation in the mitochondria, an event known to associate with the onset of apoptosis. Last, STS treatment of HeLa cells showed that apoptotic demise characterized by mitochondrial fission, cytochrome c release, and nuclear fragmentation is arrested in individual HeLa cells overexpressing StAR. Collectively, our in vivo and ex vivo evidence suggests that postinfarction expression of nonsteroidogenic StAR in cardiac fibroblasts has novel antiapoptotic activity, allowing myofibroblast precursor cells to survive the traumatized event, probably to differentiate and function in tissue repair at the infarction site.
authors.affiliation: Department of Biological Chemistry, The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem 41904, Israel.
authors.forename: Eli
authors.initials: E
authors.lastname: Anuka
authors.forename: Natalie
authors.initials: N
authors.lastname: Yivgi-Ohana
authors.forename: Sarah
authors.initials: S
authors.lastname: Eimerl
authors.forename: Benjamin
authors.initials: B
authors.lastname: Garfinkel
authors.forename: Naomi
authors.initials: N
authors.lastname: Melamed-Book
authors.forename: Elena
authors.initials: E
authors.lastname: Chepurkol
authors.forename: Dan
authors.initials: D
authors.lastname: Aravot
authors.forename: Tova
authors.initials: T
authors.lastname: Zinman
authors.forename: Asher
authors.initials: A
authors.lastname: Shainberg
authors.forename: Edith
authors.initials: E
authors.lastname: Hochhauser
authors.forename: Joseph
authors.initials: J
authors.lastname: Orly
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D005786:Gene Expression Regulation / Q000187:drug effects; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008954:Models, Biological; D009203:Myocardial Infarction / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D009206:Myocardium / Q000473:pathology / Q000648:ultrastructure; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D011994:Recombinant Proteins / Q000494:pharmacology; D013312:Stress, Physiological / Q000187:drug effects; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D000098682:Steroidogenic Acute Regulatory Protein
chemical_list: D010750:Phosphoproteins; D011994:Recombinant Proteins; D051028:bcl-2-Associated X Protein; D000098682:Steroidogenic Acute Regulatory Protein