Dietary supplementation with essential amino acids boosts the beneficial effects of rosuvastatin on mouse kidney.
Dietary supplementation with essential amino acids boosts the beneficial effects of rosuvastatin on mouse kidney.
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DOI：
10.1007/s00726-014-1772-5
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发表时间：
2014-09
期刊：
影响因子：
3.5
通讯作者：
Nisoli, Enzo
中科院分区：
文献类型：
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作者：
Corsetti, Giovanni;D'Antona, Giuseppe;Ruocco, Chiara;Stacchiotti, Alessandra;Romano, Claudia;Tedesco, Laura;Dioguardi, Francesco;Rezzani, Rita;Nisoli, Enzo
高效他汀类药物对肾功能的影响存在争议。为了解决他汀类药物对肾脏形态功能方面的影响，用瑞舒伐他汀（Rvs）处理血压正常的幼龄小鼠。此外，由于他汀类药物可能损害线粒体功能，小鼠接受富含必需氨基酸（EAAm）的氨基酸混合物的膳食补充剂，我们以前证明了这会增加肌肉中的线粒体生物合成，或者接受未补充的对照饮食1个月。线粒体的生物发生和功能，细胞凋亡和胰岛素信号通路的事件进行了研究，主要是在皮质近端小管。通过电子显微镜分析，线粒体更丰富，更异质的大小，与致密颗粒的内部基质中，在Rvs和Rvs加EAAm治疗的动物。Rvs给药增加了蛋白激酶B和内皮一氧化氮合酶磷酸化，但雷帕霉素信号通路的哺乳动物靶点不受影响。Rvs增加了sirtuin 1、过氧化物酶体增殖物激活受体γ共激活因子-1 α、细胞色素氧化酶IV型、细胞色素c和线粒体生物合成标记物的表达。皮质近端小管中葡萄糖调节蛋白75（Grp 75）、B细胞淋巴瘤2和细胞周期蛋白依赖性激酶抑制剂1的水平升高，内质网-线粒体伴侣Grp 78的表达降低。EAAm补充维持或增强了这些变化。Rvs促进线粒体生物合成，可能具有抗凋亡作用。EAAm促进这些过程，并可能有助于有效控制小鼠肾脏中的细胞能量和存活。这表明适当的营养干预可以增强Rvs的有益作用，并可能预防慢性肾脏副作用。
The effects of high-potency statins on renal function are controversial. To address the impact of statins on renal morpho-functional aspects, normotensive young mice were treated with rosuvastatin (Rvs). Moreover, because statins may impair mitochondrial function, mice received either dietary supplementation with an amino acid mixture enriched in essential amino acids (EAAm), which we previously demonstrated to increase mitochondrial biogenesis in muscle or an unsupplemented control diet for 1 month. Mitochondrial biogenesis and function, apoptosis, and insulin signaling pathway events were studied, primarily in cortical proximal tubules. By electron microscopy analysis, mitochondria were more abundant and more heterogeneous in size, with dense granules in the inner matrix, in Rvs- and Rvs plus EAAm-treated animals. Rvs administration increased protein kinase B and endothelial nitric oxide synthase phosphorylation, but the mammalian target of rapamycin signaling pathway was not affected. Rvs increased the expression of sirtuin 1, peroxisome proliferator-activated receptor γ coactivator-1α, cytochrome oxidase type IV, cytochrome c, and mitochondrial biogenesis markers. Levels of glucose-regulated protein 75 (Grp75), B-cell lymphoma 2, and cyclin-dependent kinase inhibitor 1 were increased in cortical proximal tubules, and expression of the endoplasmic reticulum–mitochondrial chaperone Grp78 was decreased. EAAm supplementation maintained or enhanced these changes. Rvs promotes mitochondrial biogenesis, with a probable anti-apoptotic effect. EAAm boosts these processes and may contribute to the efficient control of cellular energetics and survival in the mouse kidney. This suggests that appropriate nutritional interventions may enhance the beneficial actions of Rvs, and could potentially prevent chronic renal side effects.
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DOI：
10.1177/039463201102400307
发表时间：
2011-07-01
影响因子：
3.5
作者：
Corsetti, G.;Stacchiotti, A.;Rezzani, R.
通讯作者：
Rezzani, R.
DOI：
10.1007/bf00266843
发表时间：
1989-01-01
期刊：
HISTOCHEMISTRY
影响因子：
--
作者：
DAYAN, D;HISS, Y;WOLMAN, M
通讯作者：
WOLMAN, M
影响因子：
6.1
作者：
Cormack-Aboud, Fionnuala C.;Brinkkoetter, Paul T.;Durvasula, Raghu V.
通讯作者：
Durvasula, Raghu V.
影响因子：
13.6
作者：
Bussolati, B;Deregibus, MC;Camussi, G
通讯作者：
Camussi, G
影响因子：
--
作者：
BALABAN, RS;MANDEL, LJ
通讯作者：
MANDEL, LJ