Vimentin phosphorylation as a target of cell signaling mechanisms induced by 1alpha,25-dihydroxyvitamin D3 in immature rat testes.
The effects of 1alpha,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] are mainly mediated by nuclear receptors modulating gene expression. However, there are increasing evidences of nongenomic mechanisms of this hormone associated with kinase- and calcium-activated signaling pathways. In this context, the aim of the present work was to investigate the signaling pathways involved in the mechanism of action of 1,25(OH)(2)D(3) on vimentin phosphorylation in 15-day-old rat testes. Results showed that 1,25(OH)(2)D(3) at concentrations ranging from 1 nM to 1 microM increased vimentin phosphorylation independent of protein synthesis. We also demonstrated that the mechanisms underlying the hormone action involve protein kinase C activation in a phospholipase C-independent manner. Moreover, we showed that the participation of protein kinase A, extracellular regulated protein kinase (ERK), and intra- and extracellular Ca(2+) mediating the effects of 1,25(OH)(2)D(3) on the cytoskeleton. In addition, we investigated the effect of different times of exposure to the hormone on total and phosphoERK1/2 or c-Jun N-terminal kinases 1/2 (JNK1/2) in immature rat testis. Results showed that the total levels of ERK1/2 and JNK1/2 were unaltered from 1 to 15 min exposure to 1,25(OH)(2)D(3). However, the phosphoERK1/2 levels significantly increased at 1 and 5 min 1,25(OH)(2)D(3) treatment. Furthermore, phosphoJNK1 levels were decreased at 10 and 15 min 1,25(OH)(2)D(3) exposure, while phosphoJNK 2 levels were diminished at 5, 10 and 15 min treatment with the hormone. These findings demonstrate that 1,25(OH)(2)D(3) may modulate vimentin phosphorylation through nongenomic Ca(2+)-dependent mechanisms in testis cells.
Zamoner
Ariane
A
Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600 - anexo. CEP 90035-003 Porto Alegre, RS, Brazil.
Pierozan
Paula
P
Vidal
Luiza Fedatto
LF
Lacerda
Bruna Arcce
BA
Dos Santos
Natália Gomes
NG
Vanzin
Camila Simioni
CS
Pessoa-Pureur
Regina
R
D000818:Animals; D015153:Blotting, Western; D002117:Calcitriol / Q000494:pharmacology*; D020013:Calcium Signaling; D003599:Cytoskeleton / Q000378:metabolism; 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; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013737:Testis / Q000187:drug effects* / Q000378:metabolism; D010738:Type C Phospholipases / Q000378:metabolism; D014746:Vimentin / Q000378:metabolism*; D014815:Vitamins / Q000494:pharmacology*
D014746:Vimentin; D014815:Vitamins; D048056:Mitogen-Activated Protein Kinase 9; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048055:Mitogen-Activated Protein Kinase 8; D010738:Type C Phospholipases; D002117:Calcitriol