Hypoxic preconditioning induces elevated expression of stanniocalcin-1 in the heart.
Animals exposed for a few hours to low oxygen content (8%) develop resistance against further ischemic myocardial damage. The molecular mechanism(s) behind this phenomenon, known as hypoxic preconditioning (HOPC), is still incompletely understood. Stanniocalcin-1 (STC-1) is an evolutionarily conserved glycoprotein originally discovered in fish, in which it regulates calcium/phosphate homeostasis and protects against toxic hypercalcemia. Our group originally reported expression of mammalian STC-1 in brain neurons and showed that STC-1 is a prosurvival factor that guards neurons against hypercalcemic and hypoxic damage. This study investigates the involvement of STC-1 in HOPC-induced cardioprotection. Wild-type mice and IL-6-deficient (Il-6(-/-)) mice were kept in hypoxic conditions (8% O(2)) for 6 h. Myocardial Stc-1 mRNA expression was quantified during hypoxia and after recovery. HOPC triggered a biphasic upregulation of Stc-1 expression in hearts of wild-type mice but not in those of Il-6(-/-) mice. Treatment of cardiomyocyte cells in culture with hypoxia or IL-6 elicited an Stc-1 response, and ectopically expressed STC-1 in HL-1 cells localized to the mitochondria. Our findings indicate that IL-6-induced expression of STC-1 is one molecular mechanism behind the ischemic tolerance generated by HOPC in the heart.
Westberg
Johan A
JA
Department of Pathology, Haartman Institute, University of Helsinki, Finland.
Serlachius
Martina
M
Lankila
Petri
P
Andersson
Leif C
LC
D000818:Animals; D015687:Cell Hypoxia; D002478:Cells, Cultured; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism / Q000494:pharmacology; D019157:Ischemic Preconditioning, Myocardial; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008929:Mitochondria, Heart / Q000378:metabolism; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000517:prevention & control; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
D006023:Glycoproteins; D015850:Interleukin-6; D012333:RNA, Messenger; C051795:teleocalcin