Induction of Immediate Early and Stress Genes in Rat Proximal Tubule Epithelium Following Injury: The Significance of Cytosolic Ionized Calcium

Abstract

This study was designed to investigate the influence of intracellular ionized calcium ([Ca²⁺]_i) on the induction of c-fos, c-jun, c-myc, and hsp70 genes after ox-idant stress induced by xanthinelxanthine oxidase (X/XOD) treatment or after heat shock using primary cultures of rat proximal tubule epithelium (PTE). X/XOD (500 μM/25 mU/mL) induced all of these genes; ionomycin also resulted in similar kinetics of induction of all genes. The expression of both c-fos following X/XOD treatment and hsp70 following heat shock was markedly decreased through che-lation of [Ca²⁺]_i by Quin 21AM. The c-fos expression following X/XOD treatment was partly reduced by a protein kinase C inhibitor, staurosporine (ST), and markedly inhibited by another protein kinase inhibitor, 2-aminopurine (2AP), while both ST and 2AP markedly reduced hsp70 expression. The ADP-ribosylation transferase inhibitor 3-aminobenzamide had on effect on either c-fos or hsp70 expression. These results suggest that cell injuries leading to increased [Ca²⁺]_i in PTE result in induction of c-fos, c-jun, c-myc, and hsp70; and that the activation of c-fos and hsp70 genes may be regulated by [Ca²⁺]_i and [Ca²⁺]_i-dependent protein kinases.