Oxidative phosphorylation and its coupling to mitochondrial creatine and adenylate kinases in human gastric mucosa

• Published in: American journal of physiology. Regulatory, integrative and comparative physiology Vol. 291; no. 4; pp. R936 - R946
• Main Authors: Gruno, Marju, Peet, Nadezhda, Seppet, Evelin, Kadaja, Lumme, Paju, Kalju, Eimre, Margus, Orlova, Ehte, Peetsalu, Margot, Tein, Andres, Soplepmann, Jaan, Schlattner, Uwe, Peetsalu, Ants, Seppet, Enn K
• Format: Journal Article
• Language: English
• Published: United States American Physiological Society 01.10.2006
• Subjects: Adenylate Kinase; Adenylate Kinase - genetics; Adenylate Kinase - metabolism; Aged; Biochemistry, Molecular Biology; Creatine Kinase, Mitochondrial Form; Creatine Kinase, Mitochondrial Form - genetics; Creatine Kinase, Mitochondrial Form - metabolism; Cytochromes c; Cytochromes c - metabolism; Energy Metabolism; Energy Metabolism - physiology; Female; Gastric Mucosa; Gastric Mucosa - enzymology; Gene Expression Regulation, Enzymologic; Helicobacter pylori; Humans; Life Sciences; Male; Middle Aged; Mitochondria; Mitochondria - enzymology; Muscle, Smooth; Muscle, Smooth - enzymology; Oxidative Phosphorylation; Pyloric Antrum; Pyloric Antrum - enzymology
• ISSN: 0363-6119; 1522-1490
• DOI: 10.1152/ajpregu.00162.2006

1 Department of Pathophysiology, Centre of Molecular and Clinical Medicine, Faculty of Medicine, Department of Surgery, University of Tartu, Tartu, Estonia; 2 Institute of Cell Biology, ETH Zürich, Zürich, Switzerland Submitted 8 March 2006 ; accepted in final form 17 May 2006 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 kinase and adenylate kinase (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 K m 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, probably attributed to the pathogenic effects of Helicobacter pylori . Compared with 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. human stomach mucosa; corpus; antrum Address for reprint requests and other correspondence: E. K. Seppet, Dept. of Pathophysiology, Faculty of Medicine, Univ. of Tartu, 19 Ravila St., 50411 Tartu, Estonia (e-mail: enn.seppet{at}ut.ee )