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1,25-二羟维生素D3对未成熟大鼠支持细胞的信号传导:γ-谷氨酰转肽酶与葡萄糖代谢

1,25(OH)2 vitamin D3 signalling on immature rat Sertoli cells: gamma-glutamyl transpeptidase and glucose metabolism.

作者信息

Gonçalves Renata, Zamoner Ariane, Zanatta Leila, Zanatta Ana Paula, Remor Aline Pertile, da Luz Scheffer Débora, Latini Alexandra, Silva Fátima Regina Mena Barreto

机构信息

Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Campus Universitário, Bairro Trindade, Cx Postal 5069, Florianópolis, Santa Catarina, CEP: 88040-970, Brazil.

Departamento de Enfermagem, Centro de Educação Superior do Oeste, Universidade do Estado de Santa Catarina, Chapecó, Santa Catarina, Brazil.

出版信息

J Cell Commun Signal. 2017 Sep;11(3):233-243. doi: 10.1007/s12079-016-0367-1. Epub 2017 Feb 3.

Abstract

1α,25-Dihydroxyvitamin D (1,25-D) is critical for the maintenance of normal male reproduction since reduced fertility is observed in vitamin D-deficient rats. Gamma-glutamyl transpeptidase (GGT) is a membrane-bound enzyme that is localized on Sertoli cells and catalyses the transfer of the gamma-glutamyl residues to an amino acid or peptide acceptor. Sertoli cells are also responsible for providing nutrients, as lactate, to the development of germ cells. The aim of this study was to investigate the effect and the mechanism of action of 1,25-D on GGT on Sertoli cell functions from 30-day-old immature rat testis. Results demonstrated that 1,25-D stimulates GGT activity at Sertoli cells plasma membrane through a PKA-dependent mechanism of action, which was not dependent of active de novo protein synthesis. The hormone increases glucose uptake, as well as lactate production and release by Sertoli cells without altering the reactive oxygen species (ROS) generation. In addition, 1,25-D did not change reduced glutathione (GSH) amount or oxygen consumption, and diminished Sertoli cell death. These findings demonstrate that 1,25-D stimulatory effect on GGT activity, glucose uptake, LDH activity and lactate production seem to be an important contribution of Sertoli cells for germ cells nutrition and for a full and active ongoing spermatogenesis.

摘要

1α,25-二羟基维生素D(1,25-D)对维持正常雄性生殖至关重要,因为在维生素D缺乏的大鼠中观察到生育力下降。γ-谷氨酰转肽酶(GGT)是一种膜结合酶,定位于支持细胞,催化γ-谷氨酰残基向氨基酸或肽受体的转移。支持细胞还负责为生殖细胞的发育提供乳酸等营养物质。本研究的目的是探讨1,25-D对30日龄未成熟大鼠睾丸支持细胞功能中GGT的作用及其作用机制。结果表明,1,25-D通过依赖PKA的作用机制刺激支持细胞质膜上的GGT活性,这与从头合成活性蛋白无关。该激素增加支持细胞对葡萄糖的摄取,以及乳酸的产生和释放,而不改变活性氧(ROS)的产生。此外,1,25-D不会改变还原型谷胱甘肽(GSH)的量或耗氧量,并减少支持细胞死亡。这些发现表明,1,25-D对GGT活性、葡萄糖摄取、乳酸脱氢酶(LDH)活性和乳酸产生的刺激作用似乎是支持细胞对生殖细胞营养以及完整且活跃的精子发生过程的重要贡献。

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