PTH regulation of c-Jun terminal kinase and p38 MAPK cascades in intestinal cells from young and aged rats.
In the present study, we examined the role of Parathyroid hormone (PTH) on the c-Jun N-terminal kinase (JNK) 1/2 and p38 mitogen-activated protein kinase (MAPK) members of the MAPK family as it relates to ageing by measuring hormone-induced changes in their activity in enterocytes isolated from young (3 month old) and aged (24 month old) rats. Our results show that PTH induces a transient activation of JNK 1/2, peaking at 1 min (+threefold). The hormone also stimulates JNK 1/2 tyrosine phosphorylation, in a dose-dependent fashion, this effect being maximal at 10 nM. PTH-induced JNK 1/2 phosphorylation was suppressed by its selective inhibitor SP600125. Moreover, hormone-dependent activation of JNK 1/2 was dependent on calcium, since pretreatment of cells with BAPTA-AM or EGTA blocked PTH effects. With ageing, the response to PTH was significantly reduced. JNK basal protein expression was not different in the enterocytes from young and aged rats, however, basal protein phosphorylation increased with ageing. PTH did not stimulate, within 1-10 min, the basal activity and phosphorylation of p38 MAPK in rat intestinal cells. The hormone increased enterocyte DNA synthesis; the response was dose-dependent and decreased (-40%) with ageing. In agreement with the mitogenic role of the MAPK cascades, this effect was blocked by specific inhibitors of extracellular signal-regulated protein kinase (ERK) 1/2 and JNK 1/2. The results obtained in this work expand our knowledge on the mechanism of action of PTH in duodenal cells.
Buzzi
Natalia
N
Departamento de Biología, Bioquímica y Farmacia, Universidad Nacional del Sur, San Juan 670, 8000 Bahia Blanca, Argentina.
Boland
Ricardo
R
de Boland
Ana Russo
AR
D000375:Aging / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D004261:DNA Replication; D004305:Dose-Response Relationship, Drug; D004386:Duodenum / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D020895:Enterocytes / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D048055:Mitogen-Activated Protein Kinase 8 / Q000378:metabolism; D048056:Mitogen-Activated Protein Kinase 9 / Q000378:metabolism; D010281:Parathyroid Hormone / Q000378:metabolism* / Q000494:pharmacology; D010446:Peptide Fragments / Q000378:metabolism* / Q000494:pharmacology; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D010281:Parathyroid Hormone; D010446:Peptide Fragments; D048056:Mitogen-Activated Protein Kinase 9; D048031:JNK Mitogen-Activated Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048055:Mitogen-Activated Protein Kinase 8; D048051:p38 Mitogen-Activated Protein Kinases; D002118:Calcium