High Levels of Intracellular ATP Prevent Nitric Oxide-induced Apoptosis in Rat Gastric Mucosal Cells

Overview

Journal Int J Exp Pathol

Publisher Wiley

Specialty Pathology

Date 2004 Jan 30

PMID 14748747

Citations 5

Authors

Kenichi Honda

Katsuaki Kato

Naohiro Dairaku

Katsunori Iijima

Tomoyuki Koike

Akira Imatani

Hitoshi Sekine

Shuichi Ohara

Hiroshi Matsui

Tooru Shimosegawa

Affiliations

Soon will be listed here.

Abstract

Nitric oxide (NO) plays an important role in gastric mucosal injury in the human stomach. Exposure to excessive NO leads to apoptosis; however, the mechanism remains largely unknown in gastric epithelial cells. The apoptotic process is modulated by energy states in cells. This study investigated molecular mechanisms of NO-induced apoptosis in gastric epithelial cells and influence of high glucose on those mechanisms. Normal rat gastric mucosal epithelial (RGM-1) cells were cultured in media containing either 1000 (low) or 4500 mg/l (high) of D-glucose. When the cells were incubated with a chemical NO donor NOC18, apoptosis was induced in a dose-dependent manner. Intracellular adenosine triphosphate (ATP) levels significantly increased in the cells cultured with high glucose in comparison with the low-glucose condition. The cells with high ATP levels were more resistant to NO-induced apoptosis than the cells with low ATP levels. NO-induced apoptosis was followed by mitochondrial depolarization, upregulation of Bax protein, cytochrome C release from mitochondria to the cytosol and subsequent caspases activation. These results suggest that NO inhibition of mitochondrial respiratory system and acute ATP depletion initiate apoptotic signalling in gastric epithelial cells. High glucose may prevent NO-induced apoptosis by leading to high levels of intracellular ATP or other metabolic changes in this cell line.

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