期刊
BIOCHEMISTRY
卷 50, 期 47, 页码 10284-10292出版社
AMER CHEMICAL SOC
DOI: 10.1021/bi201113n
关键词
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资金
- CAPES-COFECUB [554/07]
- CNPq-Brasil [475107/2007-1]
- FAPESC-SC
1 alpha,25-Dihydroxyvitamin D-3 (1,25D(3)) is the active metabolite of vitamin D-3 and the major calcium regulatory hormone in tissues. The aim of this work was to investigate the mechanism of action of 1,25D(3) on Ca-45(2+) uptake in Sertoli cells from 30-day-old rats. Results showed that 10(-9) and 10(-12) M 1,25D(3) increased the rate of Ca-45(2+) uptake 5 and 15 min after hormone exposure and that 1 alpha,25(OH)(2) lumisterol(3) (JN) produced a similar effect suggesting that 1,25D(3) action occurs via a putative membrane receptor. The involvement of voltage-dependent calcium channels (VDCC) in 1,25D(3) action was evidenced by using nifedipine, while the use of Bapta-AM demonstrated that intracellular calcium was not implicated. Moreover, the incubation with ouabain and digoxin increased the rate of Ca-45(2+) uptake, indicating that the effect of 1,25D(3) may also result from Na+/K+-ATPase inhibition. In addition, we demonstrated that the mechanism underlying the hormone action involved extracellular signal-regulated kinase (ERK) and protein kinase C (PKC) activation in a phospholipase C-independent way. Furthermore, a local elevation of the level of cAMP, as demonstrated by incubating cells with dibutyryl cAMP or a phosphodiesterase inhibitor, produced an effect similar to that of 1,25D(3), and the inhibition of protein kinase A (PKA) nullified the hormone action. In conclusion, the stimulatory effect of 1,25D(3) on Ca-45(2+) uptake in Sertoli cells occurs via VDCC, as well as PKA, PKC, and ERK activation. These protein kinases seem to act by inhibiting Na+/K+-ATPase or directly phosphorylating calcium channels. The Na+/K+-ATPase inhibition may result in Na+/Ca2+ exchanger activation in reverse mode and consequently induce the uptake of calcium into the cells.
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