title: Allicin Protects PC12 Cells Against 6-OHDA-Induced Oxidative Stress and Mitochondrial Dysfunction via Regulating Mitochondrial Dynamics.
abstract: BACKGROUND
  Parkinson disease (PD) is a common adult-onset neurodegenerative disorder, and PD related neuronal injury is associated with oxidative stress and mitochondrial dysfunction. Allicin, the main biologically active compound derived from garlic, has been shown to exert various anti-oxidative and anti-apoptotic activities in in vitro and in vivo studies.
  
  
  METHODS
  The present study aimed to investigate the potential protective role of allicin in an in vitro PD model induced by 6-hydroxydopamine (6-OHDA) in PC12 cells. The protective effects were measured by cell viability, decreased lactate dehydrogenase (LDH) release and flow cytometry, and the anti-oxidative activity was determined by reactive oxygen species (ROS) generation, lipid peroxidation and the endogenous antioxidant enzyme activities. Mitochondrial function in PC12 cells was detected by mitochondrial membrane potential (MMP) collapse, cytochrome c release, mitochondrial ATP synthesis, and the mitochondrial Ca(2+) buffering capacity. To investigate the potential mechanism, we also measured the expression of mitochondrial biogenesis factors, mitochondrial morphological dynamic changes, as well as detected mitochondrial dynamic proteins by western blot.
  
  
  RESULTS
  We found that allicin treatment significant increased cell viability, and decreased LDH release and apoptotic cell death after 6-OHDA exposure. Allicin also inhibited ROS generation, reduced lipid peroxidation and preserved the endogenous antioxidant enzyme activities. These protective effects were associated with suppressed mitochondrial dysfunction, as evidenced by decreased MMP collapse and cytochrome c release, preserved mitochondrial ATP synthesis, and the promotion of mitochondrial Ca(2+) buffering capacity. In addition, allicin significantly enhanced mitochondrial biogenesis and prevented fragmentation of mitochondrial network after 6-OHDA treatment. The results of western blot analysis showed that the 6-OHDA induced decrease in the expression of optic atrophy type 1 (Opa-1), increase in mitochondrial fission 1 (Fis-1) and dynamin-related protein 1 (Drp-1) were all partially revised by allicin.
  
  
  CONCLUSIONS
  In summary, our data strongly suggested that allicin treatment can exert protective effects against PD related neuronal injury through inhibiting oxidative stress and mitochondrial dysfunction with dynamic changes.
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Xi'an Jiao Tong University, Xi'an, Shaanxi, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Liu
authors.forename: Ping
authors.initials: P
authors.lastname: Mao
authors.forename: Jia
authors.initials: J
authors.lastname: Wang
authors.forename: Tuo
authors.initials: T
authors.lastname: Wang
authors.forename: Chang-Hou
authors.initials: CH
authors.lastname: Xie
mesh_terms: D000255:Adenosine Triphosphate / Q000096:biosynthesis; D018663:Adrenergic Agents / Q000009:adverse effects*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D045304:Cytochromes c / Q000378:metabolism; D004220:Disulfides; D034281:Dynamins / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D020558:GTP Phosphohydrolases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D063154:Mitochondrial Dynamics / Q000187:drug effects*; D024101:Mitochondrial Proteins / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D016627:Oxidopamine / Q000009:adverse effects* / Q000037:antagonists & inhibitors; D016716:PC12 Cells; D051381:Rats; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism; D013441:Sulfinic Acids / Q000494:pharmacology*
chemical_list: D018663:Adrenergic Agents; D000975:Antioxidants; D004220:Disulfides; C503403:Fis1 protein, rat; D024101:Mitochondrial Proteins; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D013441:Sulfinic Acids; C006452:allicin; D016627:Oxidopamine; D000255:Adenosine Triphosphate; D045304:Cytochromes c; D007770:L-Lactate Dehydrogenase; D020558:GTP Phosphohydrolases; C498811:Opa1 protein, rat; C519851:Dnm1l protein, rat; D034281:Dynamins; D002118:Calcium