PTH regulation of c-Jun terminal kinase and p38 MAPK cascades in intestinal cells from young and aged rats |
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Authors: | Natalia Buzzi Ricardo Boland Ana Russo de Boland |
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Institution: | (1) Departamento de Biología, Bioquímica y Farmacia, Universidad Nacional del Sur, San Juan 670, 8000 Bahia Blanca, Argentina |
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Abstract: | 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. |
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Keywords: | PTH Enterocytes JNK p38 MAPK Proliferation Ageing |
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