The Na/K-ATPase Oxidant Amplification Loop Regulates Aging.
The Na/K-ATPase Oxidant Amplification Loop Regulates Aging.
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DOI：
10.1038/s41598-018-26768-9
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发表时间：
2018-06-26
影响因子：
4.6
通讯作者：
Shapiro JI
中科院分区：
文献类型：
--
作者：
Sodhi K;Nichols A;Mallick A;Klug RL;Liu J;Wang X;Srikanthan K;Goguet-Rubio P;Nawab A;Pratt R;Lilly MN;Sanabria JR;Xie Z;Abraham NG;Shapiro JI
由于衰老涉及氧化损伤，我们研究了最近描述的Na/K-ATPase氧化放大环(NKAL)的作用。首先，C57BL6老龄小鼠给予西式饮食刺激氧化损伤或pNaKide拮抗NKAL。西方饮食加速了衰老的功能和形态证据，而pNaKtie则减弱了这些变化。接下来，体外培养的人真皮成纤维细胞(HDF)暴露于不同类型的氧化应激中，每种氧化应激均可增加衰老标记物的表达、细胞损伤和细胞凋亡，并刺激NKAL。进一步用哇巴因刺激NKAL可促进细胞衰老，而用pNaKtie处理则可减弱细胞衰老。虽然N-乙酰半胱氨酸和维生素E也可以改善整体的氧化压力，其程度与pNaKtie相似，但pNaKtie对衰老的保护作用比任何一种抗氧化剂都要强得多。特别是，pNaKtie似乎在更大程度上特异性地改善了核氧化应激。这些数据表明，NKAL密切参与了衰老过程，并可能成为抗衰老干预的目标。
As aging involves oxidant injury, we examined the role of the recently described Na/K-ATPase oxidant amplification loop (NKAL). First, C57Bl6 old mice were given a western diet to stimulate oxidant injury or pNaKtide to antagonize the NKAL. The western diet accelerated functional and morphological evidence for aging whereas pNaKtide attenuated these changes. Next, human dermal fibroblasts (HDFs) were exposed to different types of oxidant stress in vitro each of which increased expression of senescence markers, cell-injury, and apoptosis as well as stimulated the NKAL. Further stimulation of the NKAL with ouabain augmented cellular senescence whereas treatment with pNaKtide attenuated it. Although N-Acetyl Cysteine and Vitamin E also ameliorated overall oxidant stress to a similar degree as pNaKtide, the pNaKtide produced protection against senescence that was substantially greater than that seen with either antioxidant. In particular, pNaKtide appeared to specifically ameliorate nuclear oxidant stress to a greater degree. These data demonstrate that the NKAL is intimately involved in the aging process and may serve as a target for anti-aging interventions.
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影响因子：
2.7
作者：
Bruey JM;Kantarjian H;Ma W;Estrov Z;Yeh C;Donahue A;Sanders H;O'Brien S;Keating M;Albitar M
通讯作者：
Albitar M
DOI：
10.1016/j.ejvs.2012.02.031
发表时间：
2012-06-01
影响因子：
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影响因子：
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通讯作者：
Bagrov, Alexei Y.
DOI：
10.1073/pnas.0500398102
发表时间：
2005-07-26
影响因子：
11.1
作者：
Fraga, MF;Ballestar, E;Esteller, M
通讯作者：
Esteller, M