Submitted on March 8, 2006
Accepted on May 17, 2006
Oxidative phosphorylation and its coupling to mitochondrial creatine and adenylate kinases in human gastric mucosa
Marju Gruno1, Nadezhda Peet1, Evelin Seppet1, Lumme Kadaja1, Kalju Paju1, Margus Eimre1, Ehte Orlova1, Margot Peetsalu2, Andres Tein3, Jaan Soplepmann2, Uwe Schlattner4, Ants Peetsalu2, and Enn K. Seppet1*
1 Department of Pathophysiology, University of Tartu, Tartu, Estonia
2 Department of Surgery, University of Tartu, Tartu, Estonia
3 Department of Surgery, University of Tartu, United States
4 Institute of Cell Biology, Swiss Federal Institute of Technology, Zurich, Switzerland
* To whom correspondence should be addressed. E-mail: enn.seppet{at}ut.ee.
Energy metabolism in gastrobiopsy specimens of the antral and corpus mucosa, treated with saponin to permeabilize the cells, was studied in patients with gastric diseases. The results show twice lower oxidative capacity in the antral mucosa than in the corpus mucosa, and the relative deficiency of antral mitochondria in complex I. The mucosal cells expressed mitochondrial and cytosolic isoforms of creatine (CK) and adenylate kinases (AK). Creatine (20 mM) and AMP (2 mM) markedly stimulated mitochondrial respiration in the presence of submaximal ADP or ATP concentrations, and creatine reduced apparent Km for ADP in stimulation of respiration, which indicates the functional coupling of mitochondrial kinases to oxidative phosphorylation. Addition of exogenous cytochrome c increased ADP-dependent respiration, and the large-scale cytochrome c effect (
20%) was associated with suppressed stimulation of respiration by creatine and AMP in the mucosal preparations. These results point to the impaired mitochondrial outer membrane (MOM), probably attributed to the pathogenic effects of Helicobacter pylori (H. pylori). Compared to the corpus mucosa, the antral mucosa exhibited greater sensitivity to such type of injury as the prevalence of the large-scale cytochrome c effect was twice higher among the latter specimens. Active chronic gastritis was associated with decreased respiratory capacity of the corpus mucosa but with its increase in the antral mucosa. In conclusion, human gastric mucosal cells express the mitochondrial and cytosolic isoforms of CK and AK participating in intracellular energy transfer systems. Gastric mucosa disease is associated with the altered functions of these systems and oxidative phosphorylation.
