Antioxidant supplementation normalizes elevated protein kinase C activity in the proximal tubules of old rats
Antioxidant supplementation normalizes elevated protein kinase C activity in the proximal tubules of old rats
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DOI：
10.1177/153537020422900308
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发表时间：
2004-03-01
影响因子：
3.2
通讯作者：
Lokhandwala, MF
中科院分区：
文献类型：
--
作者：
Asghar, M;Lokhandwala, MF
衰老与氧化应激的增加有关。早些时候，我们已经表明，较高的基础蛋白激酶C（PKC）活性在近端小管（PT）的老年大鼠的Na，K-ATP酶的过度磷酸化和随后的基础Na，K-ATP酶活性的降低，导致减少利钠反应多巴胺在这些动物。我们假设，增加PKC活性的老年大鼠PT是由氧化应激增加，抗氧化剂管理应减少/正常化升高的PKC活性的老年大鼠肾脏PT。我们研究了两种抗氧化剂，即a-硫辛酸（LA）和tempol，对成年（6个月）和老年（24个月）Fischer 344大鼠PT中氧化剂水平和PKC活性的影响。我们发现，荧光二氯荧光素（DCF）的积累，氧化剂生产的指标，是较高的老年大鼠相比，成年大鼠的PT。饮食补充LA 2周使老年大鼠增加的DCF水平正常化。羧甲基赖氨酸和丙二醛，氧化损伤的标志物，升高的PT的老年大鼠，这是正常化的成年大鼠的水平时，tempol提供饮用水3周。LA和tempol治疗也使老年大鼠PT中较高的基础PKC活性正常化至成年大鼠中观察到的水平。这些结果表明，氧化应激的增加导致PKC活性的增加，抗氧化剂，同时减少氧化应激，也正常化PKC活性的老年大鼠PT。
Aging is associated with increase in oxidative stress. Earlier, we have shown that higher basal protein kinase C (PKC) activity in the proximal tubules (PTs) of old rats contributes to the hyperphosphorylation of Na,K-ATPase and subsequent decrease in basal Na,K-ATPase activity, resulting in diminished natriuretic response to dopamine in these animals. We hypothesized that the increase in PKC activity in PTs of old rats is caused by increased oxidative stress and that antioxidants administration should reduce/normalize the elevated PKC activity in the renal PTs of old rats. We studied the effect of two antioxidants, namely, a-lipoic acid (LA) and tempol, on oxidants level and PKC activity in the PTs of adult (6-month) and old (24-month) Fischer 344 rats. We found that the accumulation of fluorescent dichlorofluorescein (DCF), an indicator of oxidant production, was higher in the PTs of old compared to adult rats. Dietary supplementation with LA for 2 weeks normalized the increased DCF level in old rats. Carboxymethylysine and malondialdehyde, markers of oxidative damage, were elevated in the PTs of old rats, which were normalized to the level of adult rats when tempol was provided in drinking water for 3 weeks. Both LA and tempol treatment also normalized the higher basal PKC activity in the PTs of old rats to the level seen in adult rats. These results suggest that increase in oxidative stress causes an increase in PKC activity, and that antioxidants, while reducing oxidative stress, also normalize PKC activity in the PTs of old rats.