中国神经再生研究(英文版) ›› 2016, Vol. 11 ›› Issue (8): 1247-1253.doi: 10.4103/1673-5374.189186

• 原著:神经损伤修复保护与再生 • 上一篇    下一篇

槲皮素减轻缺氧诱导神经元损伤的分子动力学模拟研究:抑制μ-钙蛋白酶

  

  • 出版日期:2016-08-31 发布日期:2016-08-31

A possible therapeutic potential of quercetin through inhibition of μ-calpain in hypoxia induced neuronal injury: a molecular dynamics simulation study

Anand Kumar Pandey1, *, #, Swet Chand Shukla2, #, Pallab Bhattacharya1, 3, #, Ranjana Patnaik1, *   

  1. 1 School of Biomedical Engineering, Indian Institute of Technology, Banaras Hindu University, Varanasi, India 2 School of Biochemical Engineering, Indian Institute of Technology, Banaras Hindu University, Varanasi, India 3 Department of Neurology, Leonard M. Miller School of Medicine, University of Miami, Miami, FL, USA
  • Online:2016-08-31 Published:2016-08-31
  • Contact: Anand Kumar Pandey, Ph.D. or Ranjana Patnaik, Ph.D., pandayanandkumar@gmail.com or rpatnaik11@gmail.com.

摘要: μ-钙蛋白酶可引起缺氧缺血脑损伤后神经元死亡,因而可作为槲皮素保护缺氧缺血损伤作用的干预靶点,但槲皮素对μ-钙蛋白酶如何发挥抑制作用的分子动力学模拟特性尚待进一步研究。实验发现,槲皮素与μ-钙蛋白酶亲合结合值达到了-28.73 kJ/mol, Ki值为 35.87 μM,这可能是槲皮素抑制μ-钙蛋白酶功能的原因,从而揭示了槲皮素以μ-钙蛋白酶干预靶点对缺氧损伤发挥保护作用的分子动力学机制。

关键词: 神经再生, 槲皮素, μ-钙蛋白酶, 分子对接, 分子动力学模拟, 缺氧, 神经保护

Abstract: The neuroprotective property of quercetin is well reported against hypoxia and ischemia in past studies. This property of quercetin lies in its antioxidant property with blood-brain barrier permeability and anti-inflammatory capabilities. μ-Calpain, a calcium ion activated intracellular cysteine protease causes serious cellular insult, leading to cell death in various pathological conditions including hypoxia and ischemic stroke. Hence, it may be considered as a potential drug target for the treatment of hypoxia induced neuronal injury. As the inhibitory property of μ-calpain is yet to be explored in details, hence, in the present study, we investigated the interaction of quercetin with μ-calpain through a molecular dynamics simulation study as a tool through clarifying the molecular mechanism of such inhibition and determining the probable sites and modes of quercetin interaction with the μ-calpain catalytic domain. In addition, we also investigated the structure-activity relationship of quercetin with μ-calpain. Affnity binding of quercetin with μ-calpain had a value of –28.73 kJ/mol and a Ki value of 35.87 μM that may be a probable reason to lead to altered functioning of μ-calpain. Hence, quercetin was found to be an inhibitor of μ-calpain which might have a possible therapeutic role in hypoxic injury.

Key words: nerve regeneration, quercetin, μ-calpain, molecular docking, molecular dynamics simulation; hypoxia, neuroprotection, neural regeneration