title: Beclin1 and HMGB1 ameliorate the α-synuclein-mediated autophagy inhibition in PC12 cells.
abstract: BACKGROUND
  Aberrant α-synuclein aggregation due to the deficiency of ubiquitin-proteasome or of autophagy characterizes the parkinson disease (PD). High mobility group box 1 (HMGB1) is a novel stress sensor to mediate the persistent neuro-inflammation and the consequent progressive neurodegeneration, via controlling the cellular autophagy/apoptosis checkpoint during inflammation. Moreover, HMGB1 has been recently indicated to involve in the autophagic degradation of α-synuclein.
  
  
  METHODS
  In the current study, we investigated the influence of the overexpressed α-synuclein of wild type (wt) or mutant type (A53T and A30P, mt) on the cytosolic levels of HMGB1 and Beclin1 and on the starvation-induced autophagy in pheochromocytoma PC12 cells. And then we explored the overexpression of HMGB1 or of Beclin1 on the α-synuclein degradation and on the autophagy in the α-synuclein-overexpressed PC12 cells.
  
  
  RESULTS
  It was demonstrated that α-synuclein overexpression inhibited the trans-location of HMGB1 from nucleus to cytosol and reduced the cytosolic level of Beclin1 in PC12 cells, and inhibited the starvation-induced autophagy via downregulating autophagy-associated markers and via reducing the autophagic vesicles in PC12 cells under starvation. On the other side, the intracellular promotion of either HMGB1 or Beclin1 upregulated the α-synuclein degradation and ameliorated the α-synuclein-mediated autophagy reduction in PC12 cells. However, the exogenous HMGB1 treatment exerted no such regulation in PC12 cells.
  
  
  CONCLUSIONS
  In summary, our study confirmed the positive regulation by HMGB1 and Beclin1 on the α-synuclein degradation and on the starvation-induced autophagy in PC12 cells, implying both markers as prominent targets to promote the α-synuclein degradation.
authors.affiliation: Department of Neurology, RuiKang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning, Guangxi, 530011, China.
authors.forename: Kaihua
authors.initials: K
authors.lastname: Wang
authors.affiliation: Department of Neurology, RuiKang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning, Guangxi, 530011, China.
authors.forename: Jianmin
authors.initials: J
authors.lastname: Huang
authors.affiliation: Southern Medical University, Guangzhou, Guangdong, 510515, China. weixiesmu@sina.com.|Department of Traditional Chinese Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, China. weixiesmu@sina.com.|School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, 510515, China. weixiesmu@sina.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Xie
authors.affiliation: Department of Neurology, RuiKang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning, Guangxi, 530011, China.
authors.forename: Longjian
authors.initials: L
authors.lastname: Huang
authors.affiliation: Department of Neurology, RuiKang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning, Guangxi, 530011, China.
authors.forename: Canhua
authors.initials: C
authors.lastname: Zhong
authors.affiliation: Guangxi University of Chinese Medicine, Nanning, Guangxi, 530001, China.
authors.forename: Zhenzhen
authors.initials: Z
authors.lastname: Chen
mesh_terms: D000310:Adrenal Gland Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D001343:Autophagy; D000071186:Beclin-1; D015972:Gene Expression Regulation, Neoplastic; D024243:HMGB1 Protein / Q000235:genetics / Q000378:metabolism*; D016716:PC12 Cells; D010673:Pheochromocytoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D059748:Proteolysis; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection; D051844:alpha-Synuclein / Q000235:genetics / Q000378:metabolism*
chemical_list: D051017:Apoptosis Regulatory Proteins; D000071186:Beclin-1; C512829:Becn1 protein, rat; D024243:HMGB1 Protein; C104200:Hbp1 protein, rat; D012333:RNA, Messenger; C497606:Snca protein, rat; D051844:alpha-Synuclein
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