Teertam Sireesh Kumar, Phanithi Prakash Babu
Department of Dermatology, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, United States.
Department of Biotechnology and Bioinformatics, School of Life Sciences, University of Hyderabad, Hyderabad, Telangana, India.
Heliyon. 2022 Dec 13;8(12):e12278. doi: 10.1016/j.heliyon.2022.e12278. eCollection 2022 Dec.
Autophagy is a catabolic process, which plays a pivotal role in neuronal homeostases. Sirtuin-1 (Sirt1, Silent information regulator family protein 1) is a protein deacetylase that is activated by nicotinamide adenine dinucleotide (NAD), is also influenced by starvation and stress response similar to autophagy. Sirt1 is necessary for the induction of autophagy and is critical for neuronal survival in neurodegeneration. The present study investigates the role of Sirt1/autophagy signaling and its possible involvement in neuronal cell death in the brains of cerebral ischemia (CI) patients.
Autopsied brain tissues from three healthy subjects and ten CI patients were obtained from National Institute of Mental Health and Neurosciences (NIMHANS); Bangalore, India. Western blotting and immunostaining were performed to assess the expression changes in Sirt1, autophagy mediators including Beclin-1, autophagy-related (Atg) proteins-3, 5, 7, 12-5, microtubule-associated protein-1A light chain3 (Lc3-I/II), and caspase-3 in stroke patients.
Our study showed that, in stroke patients, expression of Sirt1, Beclin-1, Atg-3, 5, 7, 12-5, and Lc3-II/I were upregulated. Further, our immunohistochemistry results show increased immunoreactivity of Sirt1, Beclin-1, Atg-7, Lc3-I/II, and cleaved caspase-3 in stroke brains.
The present data suggesting a role for Sirt1/autophagy signaling in regulating neuronal cell survival in CI.
自噬是一种分解代谢过程，在神经元稳态中起关键作用。沉默调节蛋白1（Sirt1，沉默信息调节因子家族蛋白1）是一种由烟酰胺腺嘌呤二核苷酸（NAD）激活的蛋白质脱乙酰酶，也受到与自噬类似的饥饿和应激反应的影响。Sirt1对自噬的诱导是必需的，对神经退行性变中的神经元存活至关重要。本研究调查Sirt1/自噬信号传导的作用及其可能参与脑缺血（CI）患者大脑中神经元细胞死亡的情况。
从印度班加罗尔国家心理健康和神经科学研究所（NIMHANS）获得3名健康受试者和10名CI患者的尸检脑组织。进行蛋白质免疫印迹和免疫染色以评估中风患者中Sirt1、自噬介质包括Beclin-1、自噬相关（Atg）蛋白-3、5、7、12-5、微管相关蛋白-1A轻链3（Lc3-I/II）和半胱天冬酶-3的表达变化。
我们的研究表明，在中风患者中，Sirt1、Beclin-1、Atg-3、5、7、12-5和Lc3-II/I的表达上调。此外，我们的免疫组织化学结果显示中风大脑中Sirt1、Beclin-1、Atg-7、Lc3-I/II和裂解的半胱天冬酶-3的免疫反应性增加。
目前的数据表明Sirt1/自噬信号传导在调节CI中神经元细胞存活方面发挥作用。
