首页> 外文期刊>Circulation: An Official Journal of the American Heart Association >Transforming growth factor-beta(1) stimulates L-arginine transport and metabolism in vascular smooth muscle cells: role in polyamine and collagen synthesis.
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Transforming growth factor-beta(1) stimulates L-arginine transport and metabolism in vascular smooth muscle cells: role in polyamine and collagen synthesis.

机译:转化生长因子-β(1)刺激L-精氨酸在血管平滑肌细胞中的运输和代谢:在多胺和胶原蛋白合成中的作用。

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BACKGROUND: Transforming growth factor-beta(1) (TGF-beta(1)) contributes to arterial remodeling by stimulating vascular smooth muscle cell (VSMC) growth and collagen synthesis at sites of vascular injury. Because L-arginine is metabolized to growth-stimulatory polyamines and to the essential collagen precursor L-proline, we examined whether TGF-beta(1) regulates the transcellular transport and metabolism of L-arginine by VSMCs. METHODS AND RESULTS: TGF-beta(1) increased L-arginine uptake, and this was associated with a selective increase in cationic amino acid transporter-1 (CAT-1) mRNA. In addition, TGF-beta(1) stimulated L-arginine metabolism by inducing arginase I mRNA and arginase activity. TGF-beta(1) also stimulated L-ornithine catabolism by elevating ornithine decarboxylase (ODC) and ornithine aminotransferase (OAT) activity. TGF-beta(1) markedly increased the capacity of VSMCs to generate the polyamine putrescine and L-proline from extracellular L-arginine. The TGF-beta(1)-mediated increase in putrescine and L-proline production was reversed by methyl-L-arginine, a competitive inhibitor of cationic amino acid transport, or by hydroxy-L-arginine, an arginase inhibitor. Furthermore, the formation of putrescine was inhibited by the ODC inhibitor alpha-difluoromethylornithine, and L-proline generation was blocked by the OAT inhibitor L-canaline. L-Canaline also inhibited TGF-beta(1)-stimulated type I collagen synthesis. CONCLUSIONS: These results demonstrate that TGF-beta(1) stimulates polyamine and L-proline synthesis by inducing the genes that regulate the transport and metabolism of L-arginine. In addition, they show that TGF-beta(1)-stimulated collagen production is dependent on L-proline formation. The ability of TGF-beta(1) to upregulate L-arginine transport and direct its metabolism to polyamines and L-proline may contribute to arterial remodeling at sites of vascular damage.
机译:背景:转化生长因子-β(1)(TGF-β(1))通过刺激血管平滑肌细胞(VSMC)的生长和血管损伤部位的胶原蛋白合成来促进动脉重构。因为L-精氨酸被代谢成促进生长的多胺和必需的胶原前体L-脯氨酸,所以我们检查了TGF-beta(1)是否通过VSMC调节L-精氨酸的跨细胞运输和代谢。方法和结果:TGF-β(1)增加L-精氨酸的摄取,这与选择性增加阳离子氨基酸转运蛋白1(CAT-1)mRNA有关。此外,TGF-beta(1)通过诱导精氨酸酶I mRNA和精氨酸酶活性来刺激L-精氨酸代谢。 TGF-beta(1)还通过提高鸟氨酸脱羧酶(ODC)和鸟氨酸转氨酶(OAT)的活性来刺激L-鸟氨酸的分解代谢。 TGF-beta(1)显着增加了VSMC从细胞外L-精氨酸生成多胺腐胺和L-脯氨酸的能力。 TGF-beta(1)介导的腐胺和L-脯氨酸产量增加被甲基-L-精氨酸(一种阳离子氨基酸转运的竞争性抑制剂)或羟基-L-精氨酸(一种精氨酸酶抑制剂)逆转。此外,ODC抑制剂α-二氟甲基鸟氨酸可抑制腐胺的形成,而OAT抑制剂L-canaline可阻止L-脯氨酸的产生。 L-Canaline还抑制TGF-β(1)刺激的I型胶原蛋白合成。结论:这些结果表明,TGF-β(1)通过诱导调节L-精氨酸转运和代谢的基因来刺激多胺和L-脯氨酸的合成。此外,他们表明,TGF-β(1)刺激胶原蛋白的生产取决于L-脯氨酸的形成。 TGF-beta(1)上调L-精氨酸转运并将其代谢定向至多胺和L-脯氨酸的能力可能有助于血管损伤部位的动脉重构。

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