Expression of the heterotrimeric G protein Gi and ATP release are impaired in erythrocytes of humans with diabetes mellitus.
Erythrocytes of humans have been reported to stimulate nitric oxide (NO) synthesis in the circulation as a consequence of their ability to release ATP in response to both mechanical deformation and exposure to reduced oxygen tension. It has been proposed that the ability of the erythrocyte to affect local vascular resistance permits it to participate in the regulation of blood flow such that oxygen delivery is matched with metabolic need. A signal transduction pathway that relates deformation and exposure to reduced oxygen tension to ATP release from human erythrocytes has been described. The heterotrimeric G protein, Gi, is a critical component of this pathway. Importantly, stimulation of Gi results in activation of adenylyl cyclase and ATP release from these cells. Recently, in a model of diabetes mellitus in rats, expression of Gi was reported to be decreased in the aorta. We report that expression of G alpha 12 is selectively decreased in erythrocytes of humans with type 2 diabetes (DM2) and that these erythrocytes fail to release ATP in response to incubation with mastoparan 7 (10 microM), an agent that activates Gi. These results provide support for the hypothesis that ATP release from erythrocytes of humans with DM2 is impaired and this defect in erythrocyte physiology could contribute to the vascular disease associated with this clinical condition.
Sprague
Randy
R
Saint Louis University, School of Medicine, Department of Pharmacological and Physiological Science, St. Louis, MO 63104, USA. spraguer@slu.edu
Stephenson
Alan
A
Bowles
Elizabeth
E
Stumpf
Madelyn
M
Ricketts
Gregory
G
Lonigro
Andrew
A
D000255:Adenosine Triphosphate / Q000737:chemistry* / Q000378:metabolism; D015153:Blotting, Western; D002462:Cell Membrane / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000473:pathology; D004912:Erythrocytes / Q000378:metabolism*; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000096:biosynthesis*; D006454:Hemoglobins / Q000378:metabolism; D020962:Heterotrimeric GTP-Binding Proteins / Q000737:chemistry*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D008954:Models, Biological; D010100:Oxygen / Q000378:metabolism; D010455:Peptides / Q000494:pharmacology; D017434:Protein Structure, Tertiary
D006454:Hemoglobins; D036341:Intercellular Signaling Peptides and Proteins; C084070:Mas7 protein, synthetic; D010455:Peptides; D000255:Adenosine Triphosphate; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D020962:Heterotrimeric GTP-Binding Proteins; D010100:Oxygen