{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T04:09:22Z","timestamp":1789445362777,"version":"build-2803163510"},"reference-count":52,"publisher":"The Company of Biologists","issue":"7","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2006,4,1]]},"abstract":"<jats:title>SUMMARY<\/jats:title><jats:p>We investigated the activation of the p38-MAPK signalling pathway during extracellular pH changes in the isolated perfused amphibian heart. Extracellular alkalosis (pH 8.5 or 9.5) maximally activated p38-MAPK within 2 min (4.17- and 3.20-fold, respectively) and this effect was reversible since the kinase phosphorylation levels decreased upon reperfusing the heart with normal Tris\u2013Tyrode's buffer. Extracellular acidosis also activated p38-MAPK moderately, but persistently (1.65-fold, at 1 min and 1.91-fold, at 60 min). The alkalosis-induced p38-MAPK activation depended upon the Na+\/H+ exchanger (NHE) and Na+\/K+-ATPase, because it was abolished when the NHE inhibitors amiloride and HOE642 and the Na+\/K+-ATPase inhibitor, ouabain, were used. Our studies also showed that extracellular alkalosis (pH 8.5) induced MAPKAPK2 phosphorylation (2.59-fold, 2 min) and HSP27 phosphorylation (5.33-fold, 2 min) in a p38-MAPK-dependent manner, as it was inhibited with 1 \u03bcmol l\u20131 SB203580. Furthermore,immunohistochemical studies of the phosphorylated forms of p38-MAPK and HSP27 revealed that these proteins were localised in the perinuclear region and dispersedly in the cytoplasm of ventricular cells during alkalosis. Finally,alkalosis induced the increase of HSP70 protein levels (1.52-fold, 5 min), but independently of p38-MAPK activation. These data indicate that the p38-MAPK signalling pathway is activated by extracellular pH changes and in the case of alkalosis this activation may have a protective role.<\/jats:p>","DOI":"10.1242\/jeb.02134","type":"journal-article","created":{"date-parts":[[2006,3,17]],"date-time":"2006-03-17T23:12:57Z","timestamp":1142637177000},"page":"1344-1354","source":"Crossref","is-referenced-by-count":22,"title":["Extracellular pH changes activate the p38-MAPK signalling pathway in the amphibian heart"],"prefix":"10.1242","volume":"209","author":[{"given":"Konstantina","family":"Stathopoulou","sequence":"first","affiliation":[{"name":"Department of Animal and Human Physiology, School of Biology, Faculty of Sciences, University of Athens, Panepistimioupolis, Athens 157 84,Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Gaitanaki","sequence":"additional","affiliation":[{"name":"Department of Animal and Human Physiology, School of Biology, Faculty of Sciences, University of Athens, Panepistimioupolis, Athens 157 84,Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isidoros","family":"Beis","sequence":"additional","affiliation":[{"name":"Department of Animal and Human Physiology, School of Biology, Faculty of Sciences, University of Athens, Panepistimioupolis, Athens 157 84,Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","reference":[{"key":"2021042510085182600_REF1","doi-asserted-by":"crossref","unstructured":"Aggeli, I.-K. S., Gaitanaki, C., Lazou, A. and Beis, I.(2001a). Activation of multiple MAPK pathways (ERKs, JNKs,p38-MAPK) by diverse stimuli in the amphibian heart. Mol. Cell. Biochem.221,63-69.","DOI":"10.1023\/A:1010933013533"},{"key":"2021042510085182600_REF2","doi-asserted-by":"crossref","unstructured":"Aggeli, I.-K. S., Gaitanaki, C., Lazou, A. and Beis, I.(2001b). Stimulation of multiple MAPK pathways by mechanical overload in the perfused amphibian heart. Am. J. Physiol.281,R1689-R1698.","DOI":"10.1152\/ajpregu.2001.281.5.R1689"},{"key":"2021042510085182600_REF3","doi-asserted-by":"crossref","unstructured":"Aggeli, I.-K. S., Gaitanaki, C., Lazou, A. and Beis, I.(2002a). Hyperosmotic and thermal stresses activate p38-MAPK in the perfused amphibian heart. J. Exp. Biol.205,443-454.","DOI":"10.1242\/jeb.205.4.443"},{"key":"2021042510085182600_REF4","doi-asserted-by":"crossref","unstructured":"Aggeli, I.-K. S., Gaitanaki, C., Lazou, A. and Beis, I.(2002b). \u03b11- and \u03b2-adrenoreceptor stimulation differentially activate p38-MAPK and atrial natriuretic peptide production in the perfused amphibian heart. J. Exp. Biol.205,2387-2397.","DOI":"10.1242\/jeb.205.16.2387"},{"key":"2021042510085182600_REF5","doi-asserted-by":"crossref","unstructured":"Aikawa, R., Nagai, T., Tanaka, M., Zou, Y., Ishihara, T.,Takano, H., Hasegawa, H., Akazawa, H., Mizukami, M., Nagai, R. et al. (2001). Reactive oxygen species in mechanical stress-induced cardiac hypertrophy. Biochem. Biophys. Res. Commun.289,901-907.","DOI":"10.1006\/bbrc.2001.6068"},{"key":"2021042510085182600_REF6","doi-asserted-by":"crossref","unstructured":"Befroy, D. E., Powell, T., Radda, G. K. and Clarke, K.(1999). Osmotic shock: modulation of contractile function, pHi,and ischemic damage in perfused guinea pig heart. Am. J. Physiol.276,H1236-H1244.","DOI":"10.1152\/ajpheart.1999.276.4.H1236"},{"key":"2021042510085182600_REF7","doi-asserted-by":"crossref","unstructured":"Bers, D. M., Barry, W. H. and Despa, S. (2003). Intracellular Na+ regulation in cardiac myocytes. Cardiovasc. Res.57,897-912.","DOI":"10.1016\/S0008-6363(02)00656-9"},{"key":"2021042510085182600_REF8","doi-asserted-by":"crossref","unstructured":"Bruey, J. M., Ducasse, C., Bonniaud, P., Ravagnan, L., Susin, S. A., Diaz-Latoud, C., Gurbuxani, S., Arrigo, A. P., Kroemer, G., Solary, E. et al. (2000). Hsp27 negatively regulates cell death by interacting with cytochrome c.Nat. Cell Biol.2, 645-652.","DOI":"10.1038\/35023595"},{"key":"2021042510085182600_REF9","doi-asserted-by":"crossref","unstructured":"Clerk, A., Fuller, S. J., Michael, A. and Sugden, P. H.(1998). Stimulation of \u201cstress-regulated\u201dmitogen-activated protein kinases (Stress-activated protein kinases\/c-Jun N-terminal Kinases and p38-Mitogen-activated protein kinases) in perfused rat hearts by oxidative and other stresses. J. Biol. Chem.273,7228-7234.","DOI":"10.1074\/jbc.273.13.7228"},{"key":"2021042510085182600_REF10","doi-asserted-by":"crossref","unstructured":"Clerk, A., Cole, S. M., Cullingford, T. E., Harrison, J. G.,Jormakka, M. and Valks, D. M. (2003). Regulation of cardiac myocyte cell death. Pharmacol. Therapeut.97,223-261.","DOI":"10.1016\/S0163-7258(02)00339-X"},{"key":"2021042510085182600_REF11","doi-asserted-by":"crossref","unstructured":"Concannon, C. G., Gorman, A. M. and Samall, A.(2003). On the role of Hsp27 in regulating apoptosis. Apoptosis8,61-70.","DOI":"10.1023\/A:1021601103096"},{"key":"2021042510085182600_REF12","doi-asserted-by":"crossref","unstructured":"Davis, R. J. (1994). MAPKs: new JNK expands the group. Trends Biochem. 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