title: Participation of p38 MAPK and a novel-type protein kinase C in the control of mitochondrial Ca2+ uptake.
abstract: Angiotensin II elicits cytosolic and mitochondrial Ca2+ signal in H295R adrenocortical cells. We found that Ca2+ uptake rate and peak values in small mitochondrial regions both depend on the colocalization of these mitochondrial regions with GFP-marked endoplasmic reticular (ER) vesicles. The dependence of the Ca2+ response on this colocalization is abolished by SB202190 and PD169316, inhibitors of p38 MAPK, as well as by transfection with siRNA against p38 MAPK mRNA. The same manoeuvres result in an increased ratio of global mitochondrial to global cytosolic Ca2+ response, indicating that inhibition of p38 MAPK is followed by enhanced mitochondrial Ca2+ uptake. alpha-Toxin and TNFalpha, agents which similarly to angiotensin II increase the phosphorylation of p38, failed to affect mitochondrial Ca2+ uptake, indicating that activation of p38 MAPK is necessary but not sufficient for the inhibition of Ca2+ uptake. Bisindolylmaleimide, an inhibitor of the conventional and novel-type protein kinase C isoforms also evokes enhanced mitochondrial Ca2+ uptake, whereas Gö6976 that inhibits the conventional isoforms only failed to exert any effect. These data show that angiotensin II attenuates Ca2+ uptake predominantly into mitochondria that do not colocalize with ER, by a mechanism involving p38 MAPK and a novel-type PKC.
authors.affiliation: Department of Physiology, Faculty of Medicine, Semmelweis University and Laboratory of Neurobiochemistry and Molecular Physiology, Hungarian Academy of Sciences, PO Box 259, H-1444 Budapest, Hungary.
authors.forename: Gergo
authors.initials: G
authors.lastname: Szanda
authors.forename: Péter
authors.initials: P
authors.lastname: Koncz
authors.forename: Anikó
authors.initials: A
authors.lastname: Rajki
authors.forename: András
authors.initials: A
authors.lastname: Spät
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology; D001427:Bacterial Toxins / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects; D002460:Cell Line; D003600:Cytosol / Q000187:drug effects / Q000201:enzymology; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D015151:Immunoblotting; D007527:Isoenzymes / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D051744:Protein Kinase C-epsilon / Q000037:antagonists & inhibitors / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D001427:Bacterial Toxins; D007527:Isoenzymes; D047428:Protein Kinase Inhibitors; D034741:RNA, Small Interfering; D014409:Tumor Necrosis Factor-alpha; D000804:Angiotensin II; D051744:Protein Kinase C-epsilon; D048051:p38 Mitogen-Activated Protein Kinases; D002118:Calcium