Submitted on January 5, 2007
Accepted on June 11, 2007
Hypoxic preconditioning induces elevated expression of stanniocalcin-1 in the heart
Johan A Westberg1, Martina Serlachius1, Petri Lankila1, and Leif C Andersson1*
1 Dept. of Pathology, Haartman Institute, University of Helsinki and HUSLAB, Helsinki, Finland
* To whom correspondence should be addressed. E-mail: leif.andersson{at}helsinki.fi.
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. We originally reported expression of mammalian STC-1 in brain neurons and showed that STC-1 is a pro-survival factor that guards neurons against hypercalcemic and hypoxic damage. This study investigates the involvement of STC-1 in HOPC-induced cardioprotection. Wild-type (WT) mice and IL-6-deficient mice were kept in hypoxic conditions (8% O2) for 6 hours. Myocardial Stc-1 mRNA expression was quantified during hypoxia and after recovery. HOPC triggered a biphasic upregulation of Stc-1 expression in the heart of WT mice, but not of IL-6-/- mice. Treatment of cardiomyocyte cells in culture with hypoxia or IL-6 elicited a 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.
