Senescence marker protein-30 (SMP30) enhances the calcium efflux from renal tubular epithelial cells

Abstract

Background. Senescence marker protein-30 (SMP30), a calcium binding protein, is preferentially expressed in the renal proximal tubules and hepatocytes and is presumed to play a role in Ca²⁺ homeostasis.

Methods. To explore its physiological functions in the tubular cells, we investigated the effect of SMP30 on Ca²⁺ efflux via the ATP-dependent plasma membrane calcium pump. LLC-PK1 cells were stably transfected with a cDNA encoding SMP30, and the established transfectants were subjected to ATP responses.

Results. Overexpression of SMP30 significantly increased Ca²⁺ efflux under both basal and ATP-stimulated conditions. Inhibition of calmodulin by trifluoperazine abrogated the enhanced Ca²⁺ efflux, suggesting that SMP30 activated the calmodulin-dependent Ca²⁺ pump. It is known that Ca²⁺ superfluous influx induces cellular injury. Compared with mock-transfected cells, LLC-PK1 cells expressing SMP30 showed resistance to cellular death triggered by Ca²⁺ superfluous influx.

Conclusion. These results suggest the possibility that, in renal tubular cells, endogenous SMP30 participates in Ca²⁺ efflux via activating the calmodulin-dependent Ca²⁺ pump and thereby confers resistance of the cells against injury caused by high intracellular Ca²⁺ concentrations.