Glucose and glutamine handling in the Sertoli cells of transgenic rats overexpressing regucalcin: plasticity towards lactate production.

Glucose and glutamine handling in the Sertoli cells of transgenic rats overexpressing regucalcin: plasticity towards lactate production.
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DOI:
10.1038/s41598-018-28668-4
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发表时间:
2018-07-09
期刊:
影响因子:
4.6
通讯作者:
Socorro S
Socorro S
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Mateus I;Feijó M;Espínola LM;Vaz CV;Correia S;Socorro S

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支持细胞(SC)具有无与伦比的能力,提供生殖细胞生长因子和营养物质。虽然SC可以氧化氨基酸,例如,除了谷氨酰胺外,它们主要代谢葡萄糖,产生大量的乳酸盐,乳酸盐是生殖细胞的优先底物。Regucalcin(RGN)是一种钙结合蛋白,已被指示为细胞代谢的调节剂。在这项研究中,我们研究了葡萄糖和谷氨酰胺处理的SC过表达RGN(TG-RGN)的转基因大鼠相比,野生型(Wt)的同窝仔。从成年Tg-RGN动物中分离并在培养物中保持24小时的原代SC产生并输出更多的乳酸,尽管消耗较少的葡萄糖。这些观察结果得到了丙氨酸转氨酶表达增加和谷氨酰胺消耗增加的支持,表明替代途径有助于提高Tg-RGN大鼠SC中的乳酸产生。此外,乳酸盐似乎被生殖细胞使用,在离体培养的Tg-RGN动物的生精小管中检测到细胞凋亡减少。结果表明,Wt和Tg-RGN大鼠的SC中存在不同的代谢,从而扩大了RGN在精子发生中的作用。这些发现还强调了SC代谢的可塑性,这一特征将在男性不育症的背景下被利用。
Sertoli cells (SCs) possess the unparalleled ability to provide the germ line with growth factors and nutrients. Although SCs can oxidize amino acids, e.g., glutamine, they mostly metabolize glucose, producing high amounts of lactate, the germ cells preferential substrate. Regucalcin (RGN) is a calcium-binding protein that has been indicated as a regulator of cell metabolism. In this study, we investigated glucose and glutamine handling in the SCs of transgenic rats overexpressing RGN (Tg-RGN) comparatively with wild-type (Wt) littermates. Primary SCs isolated from adult Tg-RGN animals and maintained in culture for 24 hours, produced and exported more lactate, despite consuming less glucose. These observations were underpinned by increased expression of alanine transaminase, and augmented glutamine consumption, suggesting that alternative routes are contributing to the enhanced lactate production in the SCs of Tg-RGN rats. Moreover, lactate seems to be used by germ cells, with diminished apoptosis being detected in the seminiferous tubules of Tg-RGN animals cultured ex vivo. The obtained results showed a distinct metabolism in the SCs of Wt and Tg-RGN rats widening the roles assigned to RGN in spermatogenesis. These findings also highlighted the plasticity of SCs metabolism, a feature that would be exploited in the context of male infertility.
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