中国神经再生研究(英文版) ›› 2019, Vol. 14 ›› Issue (6): 975-976.doi: 10.4103/1673-5374.250575

• 观点:退行性病与再生 • 上一篇    下一篇

帕金森病中蛋白质乙酰化的范例

  

  • 出版日期:2019-06-15 发布日期:2019-06-15

The paradigm of protein acetylation in Parkinson’s disease

Sokhna M.S. Yakhine-Diop, Guadalupe Martínez-Chacón, Elisabet Uribe-Carretero, Mireia Niso-Santano, Rosa A. González-Polo, José M. Fuentes   

  1. Universidad de ExtremaduraDepartamento de Bioquímica y Biología Molecular y Genética, Facultad de Enfermería y Terapia Ocupacional, Cáceres, Spain; Centro de Investigación Biomédica en Red en Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain;  Instituto de Investigación Biosanitaria de Extremadura (INUBE), Spain
  • Online:2019-06-15 Published:2019-06-15
  • Contact: Rosa A. González-Polo, PhD, jfuentes@unex.es; José M. Fuentes, PhD, rosapolo@unex.es.
  • Supported by:

    from Junta de Extremadura. JM.F. received research support from the Instituto de Salud Carlos III, CIBERNED (CB06/05/004) and Instituto de Salud Carlos III, FIS, (PI15/00034). This work was also supported by “Fondo Europeo de Desarrollo Regional” (FEDER) from the European Union. The authors also thank FUNDESALUD for helpful assistance.

摘要:

orcid: 0000-0001-6910-2089 (José M. Fuentes)
           0000-0002-0163-2953 (Rosa A. González-Polo)

Abstract:

Acetylation is a post-translational modification that is regulated by two antagonistic enzymes, histone acetyltransferases (HATs) and histone deacetylases (HDACs). HATs transfer the acetyl group from acetyl-CoA to lysine residues of proteins while HDACs remove it. The impairment of HAT or HDAC activity elicits changes in the protein acetylation status which disturb several cellular processes, among others, gene expression, autophagy etc., leading finally to cell death. Both enzymes are associated with Parkinson’s disease (PD) pathogenesis. In dopaminergic cells, neurotoxins provoke apoptotic cell death by increasing histone acetylation levels. While paraquat and rotenone reduce HDAC activity, dieldrin enhances HAT activity. However in vivo, paraquat-induced upregulation of α-synuclein triggers histone hypoacetylation. Therefore, in PD models, proteins are hypoacetylated or hyperacetylated in response to a stimulus. All these controversies become a paradigm given that a HDAC inhibitor as well as a HAT inhibitor can be cytoprotective. Most of the studies that link acetylation to PD generally focus on the level of histone acetylation. Recently, a comparative study has been performed in two groups of fibroblasts from PD patients with or without the G2019S leucine-rich repeat kinase 2 (LRRK2) mutation. This is the first time that, by western-blotting, a smear of acetylated proteins as a whole reveals the difference between idiopathic (WT LRRK2) PD (IPD) and genetic (G2019S LRRK2) PD (GPD) under basal conditions. Those changes were more evident with higher molecular weight (MW) proteins displaying a hypoacetylation in IPD and a hyperacetylation in GPD cells. With peptides subjected to LC-MS, we also observed that hypoacetylated peptides were more abundant in IPD cells than in GPD.