title: Proteomic analysis reveals differentially regulated protein acetylation in human amyotrophic lateral sclerosis spinal cord.
abstract: Amyotrophic lateral sclerosis (ALS) is a progressive fatal neurodegenerative disease that primarily affects motor neurons in the brain and spinal cord. Histone deacetylase (HDAC) inhibitors have neuroprotective effects potentially useful for the treatment of neurodegenerative diseases including ALS; however, the molecular mechanisms underlying their potential efficacy is not well understood. Here we report that protein acetylation in urea-soluble proteins is differently regulated in post-mortem ALS spinal cord. Two-dimensional electrophoresis (2-DE) analysis reveals several protein clusters with similar molecular weight but different charge status. Liquid chromatography and tandem mass spectrometry (LC-MS/MS) identifies glial fibrillary acidic protein (GFAP) as the dominant component in the protein clusters. Further analysis indicates six heavily acetylated lysine residues at positions 89, 153, 189, 218, 259 and 331 of GFAP. Immunoprecipitation followed by Western blotting confirms that the larger form of GFAP fragments are acetylated and upregulated in ALS spinal cord. Further studies demonstrate that acetylation of the proteins additional to GFAP is differently regulated, suggesting that acetylation and/or deacetylation play an important role in pathogenesis of ALS.
authors: Visiting scholars from Departments of Hepatobiliary Surgery, Gastroenterology and Neurosurgery, Xijing Hospital, Fourth Military Medical University, Xian, Shaanxi, China ; Departments of Surgery, Neurology and Urology, VA Boston Healthcare System and Boston University School of Medicine, Boston, Massachusetts, United States of America.
authors: Dong
authors: D
authors: Liu
authors: Chaoxu
authors: C
authors: Liu
authors: Junqiang
authors: J
authors: Li
authors: Kazem
authors: K
authors: Azadzoi
authors: Yun
authors: Y
authors: Yang
authors: Zhou
authors: Z
authors: Fei
authors: Kefeng
authors: K
authors: Dou
authors: Neil W
authors: NW
authors: Kowall
authors: Han-Pil
authors: HP
authors: Choi
authors: Fernando
authors: F
authors: Vieira
authors: Jing-Hua
authors: JH
authors: Yang
mesh_terms: D000107:Acetylation; D000690:Amyotrophic Lateral Sclerosis / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D040901:Proteomics; D013116:Spinal Cord / Q000378:metabolism* / Q000473:pathology
chemical_list: D009419:Nerve Tissue Proteins