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.