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干细胞中的概率调控:线粒体抗氧化酶锰超氧化物歧化酶作用的见解

Managing odds in stem cells: insights into the role of mitochondrial antioxidant enzyme MnSOD.

作者信息

Sheshadri Preethi, Kumar Anujith

机构信息

a School of Regenerative Medicine , Manipal University , Bangalore , Karnataka , India.

出版信息

Free Radic Res. 2016;50(5):570-84. doi: 10.3109/10715762.2016.1155708.

Abstract

Reactive oxygen species (ROS) have been poised at a straddled state of being beneficiary as well detrimental depending on its threshold levels. Maintaining the homeostasis of ROS is imperative for normal cellular physiology, wherein physiological concentrations of ROS are involved in cell signaling and elevated ROS contribute to the development of various diseases. Superoxide dismutases (SODs), enzymes involved in dismutation of superoxide anion to hydrogen peroxide, arrive as a first line of defense when there is perturbation in the homeostasis of ROS. As mitochondria are the main site of superoxide production, among SODs, mitochondrial manganese SOD (MnSOD) is the primary antioxidant enzyme that protects cells from ROS. Most importantly, knockout of MnSOD leads to postnatal lethality and tissue-specific conditional knockout in brain resulted in death of mice, conclusively portraying the essential role of MnSOD in development. Although MnSOD has been extensively discussed with the purview of tumor biology and aging, understanding the crucial role of MnSOD in stem cell physiology is still at its infant stage. Ever increasing progress in stem cell research has recently unveiled the essential role of MnSOD in self-renewal and differentiation of stem cells. In this review, we will conglomerate the current aspects by which MnSOD can contribute to embryonic stem cells' and adult stem cells' functions and interpret the necessity of understanding MnSOD for further stem cell mediated applications.

摘要

活性氧(ROS)根据其阈值水平处于一种既有益又有害的跨界状态。维持ROS的体内平衡对于正常细胞生理至关重要,其中ROS的生理浓度参与细胞信号传导,而ROS水平升高则会导致各种疾病的发生。超氧化物歧化酶(SOD)是参与将超氧阴离子歧化为过氧化氢的酶,当ROS体内平衡受到干扰时,它作为第一道防线发挥作用。由于线粒体是超氧产生的主要部位,在SOD中,线粒体锰超氧化物歧化酶(MnSOD)是保护细胞免受ROS侵害的主要抗氧化酶。最重要的是,MnSOD基因敲除会导致出生后死亡,而在大脑中进行组织特异性条件性敲除会导致小鼠死亡,这最终描绘了MnSOD在发育中的重要作用。尽管MnSOD已在肿瘤生物学和衰老的范围内进行了广泛讨论,但了解MnSOD在干细胞生理学中的关键作用仍处于起步阶段。干细胞研究的不断进展最近揭示了MnSOD在干细胞自我更新和分化中的重要作用。在这篇综述中,我们将总结MnSOD对胚胎干细胞和成人干细胞功能产生影响的当前研究情况,并解释理解MnSOD对于进一步的干细胞介导应用的必要性。

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