High levels of intracellular ATP prevent nitric oxide-induced apoptosis in rat gastric mucosal cells.
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.
Honda
Kenichi
K
Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.
Kato
Katsuaki
K
Dairaku
Naohiro
N
Iijima
Katsunori
K
Koike
Tomoyuki
T
Imatani
Akira
A
Sekine
Hitoshi
H
Ohara
Shuichi
S
Matsui
Hiroshi
H
Shimosegawa
Tooru
T
D000255:Adenosine Triphosphate / Q000032:analysis / Q000502:physiology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D020169:Caspases / Q000378:metabolism; D002460:Cell Line; D003470:Culture Media; D004305:Dose-Response Relationship, Drug; D005753:Gastric Mucosa / Q000166:cytology* / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology; D009569:Nitric Oxide / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009603:Nitroso Compounds / Q000494:pharmacology; D051381:Rats
D003470:Culture Media; C093285:NOC 18; D020030:Nitric Oxide Donors; D009603:Nitroso Compounds; D009569:Nitric Oxide; D000255:Adenosine Triphosphate; D020169:Caspases; D005947:Glucose