title: The Rho kinase inhibitor Y-27632 increases erythrocyte deformability and low oxygen tension-induced ATP release.
abstract: Low oxygen (O(2)) tension and mechanical deformation are stimuli for ATP release from erythrocytes. It has been shown previously that rabbit erythrocytes made less deformable with diamide, a thiol cross-linking agent, release less ATP in response to low O(2) tension, suggesting a link between these two stimuli. In nonerythroid cells, activation of the Rho/Rho kinase signaling pathway has been reported to decrease cell deformability by altering Rho kinase-dependent cytoskeleton-protein interactions. We investigated the hypothesis that the Rho kinase inhibitor Y-27632 would increase erythrocyte deformability and thereby increase low O(2) tension-induced ATP release from erythrocytes. Here we show that Y-27632 (1 μM) increases erythrocyte deformability (5%) and increases low O(2) tension-induced ATP release (203%) from healthy human erythrocytes. In addition, we found that, when erythrocytes were made less deformable by incubation with diamide (100 μM), Y-27632 restored both deformability and low O(2) tension-induced ATP release to levels similar to those measured in the absence of diamide. These findings suggest that the Rho kinase inhibitor Y-27632 is able to reverse the diamide-induced decrease in erythrocyte deformability and rescue low O(2) tension-induced ATP release. These results further support a link between erythrocyte deformability and ATP release in response to low O(2) tension.
authors: Department of Pharmacological and Physiological Science, St. Louis University School of Medicine, St. Louis, MO 63104, USA. thuetk@slu.edu
authors: K M
authors: KM
authors: Thuet
authors: E A
authors: EA
authors: Bowles
authors: M L
authors: ML
authors: Ellsworth
authors: R S
authors: RS
authors: Sprague
authors: A H
authors: AH
authors: Stephenson
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000577:Amides / Q000494:pharmacology*; D015687:Cell Hypoxia; D003432:Cross-Linking Reagents / Q000494:pharmacology; D003958:Diamide / Q000494:pharmacology; D004907:Erythrocyte Deformability / Q000187:drug effects*; D004912:Erythrocytes / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D010100:Oxygen / Q000378:metabolism*; D010455:Peptides / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology*; D013439:Sulfhydryl Reagents / Q000494:pharmacology; D014862:Wasp Venoms / Q000494:pharmacology; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
chemical_list: D000577:Amides; D003432:Cross-Linking Reagents; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D013439:Sulfhydryl Reagents; D014862:Wasp Venoms; D003958:Diamide; C066737:RHOA protein, human; C108830:Y 27632; C037500:mastoparan; D000255:Adenosine Triphosphate; D054460:rho-Associated Kinases; D020742:rhoA GTP-Binding Protein; D010100:Oxygen