title: p38 MAPK activation and function following osmotic shock of erythrocytes.
abstract: p38 protein kinase is activated by hyperosmotic shock, participates in the regulation of cell volume sensitive transport and metabolism and is involved in the regulation of various physiological functions including cell proliferation and apoptosis. Similar to apoptosis of nucleated cells, erythrocytes may undergo suicidal death or eryptosis, which is paralleled by cell shrinkage and cell membrane scrambling with phosphatidylserine exposure at the cell surface. Triggers of eryptosis include hyperosmotic shock, which increases cytosolic Ca(2+) activity and ceramide formation. The present study explored whether p38 kinase is expressed in human erythrocytes, is activated by hyperosmotic shock and participates in the regulation of eryptosis. Western blotting was utilized to determine phosphorylation of p38 kinase, forward scatter to estimate cell volume, annexin V binding to depict phosphatidylserine exposure and Fluo3 fluorescence to estimate cytosolic Ca(2+) activity. As a result, erythrocytes express p38 kinase, which is phosphorylated upon osmotic shock (+550 mM sucrose). Osmotic shock decreased forward scatter, increased annexin V binding and increased Fluo3 fluorescence, all effects significantly blunted by the p38 kinase inhibitors SB203580 (2 μM) and p38 Inh III (1 μM). In conclusion, p38 kinase is expressed in erythrocytes and participates in the machinery triggering eryptosis following hyperosmotic shock.
authors.affiliation: Department of Physiology, University of Tübingen, Tübingen, Germany.
authors.forename: Sergios
authors.initials: S
authors.lastname: Gatidis
authors.forename: Christine
authors.initials: C
authors.lastname: Zelenak
authors.forename: Abul
authors.initials: A
authors.lastname: Fajol
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Lang
authors.forename: Kashif
authors.initials: K
authors.lastname: Jilani
authors.forename: Diana
authors.initials: D
authors.lastname: Michael
authors.forename: Syed M
authors.initials: SM
authors.lastname: Qadri
authors.forename: Florian
authors.initials: F
authors.lastname: Lang
mesh_terms: D000814:Aniline Compounds / Q000737:chemistry; D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis; D002118:Calcium / Q000378:metabolism; D048429:Cell Size; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004912:Erythrocytes / Q000187:drug effects / Q000201:enzymology*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D009997:Osmotic Pressure; D010718:Phosphatidylserines / Q000494:pharmacology; D010766:Phosphorylation; D011485:Protein Binding; D011725:Pyridines / Q000494:pharmacology; D014966:Xanthenes / Q000737:chemistry; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D000814:Aniline Compounds; D017304:Annexin A5; D004791:Enzyme Inhibitors; D007093:Imidazoles; D010718:Phosphatidylserines; D011725:Pyridines; D014966:Xanthenes; C059715:Fluo-3; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580; D002118:Calcium