Involvement of human heat shock protein 90α in nicotine-induced apoptosis

✍ Scribed by Yu-ping Wu; Kazuko Kita; Nobuo Suzuki

• Publisher: John Wiley and Sons
• Year: 2002
• Tongue: French
• Weight: 272 KB
• Volume: 100
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/ijc.10449

✦ Synopsis

Abstract

There have been conflicting reports of the apoptotic effects of nicotine on human cells and those studies reporting nicotine‐induced apoptosis have not unequivocally clarified the molecular mechanisms underlying the effect. However, we found here that human RSa cells, established from embryonic fibroblastic cells doubly infected with Rous sarcoma virus and Simian virus 40, underwent apoptosis when cultured with medium containing 0.06–0.6 μM nicotine. The apoptosis was assessed by cellular DNA fragmentation and caspase‐3 protease activation. Viability of RSa cells was reduced by nicotine treatment, as analyzed by MTT assay and the reduction was lessened by combination treatment with a caspase‐3 inhibitor, acetyl‐L‐aspartyl‐L‐glutamyl‐L‐valyl‐L‐aspart‐1‐al (Ac‐DEVD‐CHO). Levels of expression of heat shock protein 90α (Hsp90α) were found to be increased 20 min after the nicotine treatment, as analyzed by polymerase chain reaction‐based mRNA differential display after Northern blotting analysis of mRNA amounts. Cellular contents of Hsp90α were furthermore increased in the nicotine‐treated RSa cells, as quantitated by Western immunoblot analysis. By contrast, in RSa cells treated with nicotine in combination with geldanamycin (GA), an inhibitor of Hsp90α function, DNA fragmentation was not detected and caspase‐3 protease activity levels were the same as those of mock‐treated cells. Nicotine‐induced caspase‐3 activation and Hsp90α expression, as well as suppression of the induction by GA, were also observed in a xeroderma pigmentosum patient‐derived cell line, XP2OS cells. Thus, it was suggested that nicotine induces apoptosis, possibly via Hsp90α expression, in human cells tested. © 2002 Wiley‐Liss, Inc.