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 oxidant stress induced by xanthine/xanthine oxidase (X/XOD) treatment or after heat shock using primary cultures of rat proximal tubule epithelium (PTE). X/XOD (500 microM/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 chelation of [Ca2+]i by Quin 2/AM. 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 no 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.

• Authors: N Yamamoto, A Maki, J D Swann, I K Berezesky, B F Trump
• Journal: Renal failure (Ren Fail) Vol. 15 Issue 2 Pg. 163-71 ( 1993) ISSN: 0886-022X [Print] England
• PMID: 8469783 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Heat-Shock Proteins
• Ions
• Xanthines
• Xanthine
• Xanthine Oxidase
• Calcium

Topics

• Animals
• Calcium (metabolism)
• Cells, Cultured (drug effects, metabolism)
• Cytosol (drug effects, metabolism)
• Epithelium (drug effects, metabolism)
• Gene Expression Regulation (drug effects, physiology)
• Heat-Shock Proteins (biosynthesis, genetics)
• Ions
• Kidney Tubules, Proximal (drug effects, metabolism)
• Male
• Proto-Oncogenes (drug effects, physiology)
• Rats
• Rats, Inbred F344
• Stress, Physiological (genetics, metabolism)
• Xanthine
• Xanthine Oxidase (pharmacology)
• Xanthines (pharmacology)