Preventing Oxidative Stress in the Liver: An Opportunity for GLP-1 and/or PASK.
Preventing Oxidative Stress in the Liver: An Opportunity for GLP-1 and/or PASK.
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DOI：
10.3390/antiox10122028
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发表时间：
2021-12-20
期刊：
影响因子：
--
通讯作者：
Sanz C
中科院分区：
文献类型：
--
作者：
Hurtado-Carneiro V;Dongil P;Pérez-García A;Álvarez E;Sanz C
肝脏的高代谢活性和解毒功能主要通过肝细胞线粒体的氧化磷酸化产生活性氧。相反，它还具有有效的抗氧化机制，可以平衡氧化剂的作用并缓解氧化应激。 PAS 激酶 (PASK) 是一种丝氨酸/苏氨酸激酶，含有 N 末端 Per-Arnt-Sim (PAS) 结构域，能够检测氧化还原状态。在禁食/进食变化期间，PASK 调节参与碳水化合物和脂质代谢以及线粒体生物合成的关键肝脏蛋白的表达和激活。有趣的是，PASK 的功能失活可以防止高脂饮食 (HFD) 引起的肥胖和糖尿病的发生。此外，PASK 缺乏会改变其他营养传感器的活性，例如 AMP 激活蛋白激酶 (AMPK) 和哺乳动物雷帕霉素靶标 (mTOR)。除了烟酰胺依赖性组蛋白脱乙酰酶 (SIRT) 的表达和亚细胞定位。本综述重点关注氧化应激、PASK 和其他营养传感器之间的关系，更新了有关 PASK 在抗氧化反应中作用的有限知识。我们还评论了胰高血糖素样肽 1 (GLP-1) 及其与 PASK 在预防肝氧化应激相关损伤方面的合作。目前的知识表明，PASK 抑制和/或 exendin-4 治疗，尤其是在禁食条件下，可以改善与过度氧化应激相关的疾病。
The liver’s high metabolic activity and detoxification functions generate reactive oxygen species, mainly through oxidative phosphorylation in the mitochondria of hepatocytes. In contrast, it also has a potent antioxidant mechanism for counterbalancing the oxidant’s effect and relieving oxidative stress. PAS kinase (PASK) is a serine/threonine kinase containing an N-terminal Per-Arnt-Sim (PAS) domain, able to detect redox state. During fasting/feeding changes, PASK regulates the expression and activation of critical liver proteins involved in carbohydrate and lipid metabolism and mitochondrial biogenesis. Interestingly, the functional inactivation of PASK prevents the development of a high-fat diet (HFD)-induced obesity and diabetes. In addition, PASK deficiency alters the activity of other nutrient sensors, such as the AMP-activated protein kinase (AMPK) and the mammalian target of rapamycin (mTOR). In addition to the expression and subcellular localization of nicotinamide-dependent histone deacetylases (SIRTs). This review focuses on the relationship between oxidative stress, PASK, and other nutrient sensors, updating the limited knowledge on the role of PASK in the antioxidant response. We also comment on glucagon-like peptide 1 (GLP-1) and its collaboration with PASK in preventing the damage associated with hepatic oxidative stress. The current knowledge would suggest that PASK inhibition and/or exendin-4 treatment, especially under fasting conditions, could ameliorate disorders associated with excess oxidative stress.
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影响因子：
3.7
作者：
Cuthbertson DJ;Irwin A;Gardner CJ;Daousi C;Purewal T;Furlong N;Goenka N;Thomas EL;Adams VL;Pushpakom SP;Pirmohamed M;Kemp GJ
通讯作者：
Kemp GJ
DOI：
10.1084/jem.20081297
发表时间：
2008-09-29
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Chen C;Liu Y;Liu R;Ikenoue T;Guan KL;Liu Y;Zheng P
通讯作者：
Zheng P
影响因子：
5.6
作者：
Cheng CF;Ku HC;Lin H
通讯作者：
Lin H
影响因子：
4.5
作者：
Grabowska W;Sikora E;Bielak-Zmijewska A
通讯作者：
Bielak-Zmijewska A
影响因子：
5.7
作者：
Amezcua, CA;Harper, SM;Gardner, KH
通讯作者：
Gardner, KH