Antioxidant action of 7,8-dihydroxyflavone protects PC12 cells against 6-hydroxydopamine-induced cytotoxicity.
Oxidative stress-induced neuronal death plays a pivotal role in pathogenesis of neurodegenerative disorders. Recently, 7,8-dihydroxyflavone (7,8-DHF) has been shown to exert neuroprotective effects by acting as a selective tyrosine kinase receptor B (TrkB) agonist. In addition, the antioxidant action of 7,8-DHF may protect neuronal cells against oxidative injury. In the present study, we used PC12 cells, a cell line generally thought to lack TrkB, to investigate the effect of 7,8-DHF on 6-hydroxydopamine (6-OHDA)-induced cytotoxicity and the underlying mechanism. We found that 7,8-DHF effectively prevented cell death, apoptosis and mitochondrial dysfunction induced by 6-OHDA. In a cell free system, 7,8-DHF did not slow down extracellular auto-oxidation of 6-OHDA which may generate H2O2. However, We found that 7,8-DHF dramatically reduced cellular malondialdehyde content and phospho-histone H2A.X protein level. 7,8-DHF also elevated total superoxide dismutase activity in 6-OHDA-treated cells. These results indicate that 7,8-DHF might protect PC12 cells against 6-OHDA-induced cytotoxicity through its powerful antioxidant activity. By acting as a potent TrkB agonist and an antioxidant together with its easiness to pass across blood-brain barrier, 7,8-DHF may be developed into a promising candidate in treatment of neurodegenerative diseases.
Department of Physiology, Qingdao University Medical College, Qingdao, PR China. Electronic address: xiaohua.han@163.com.
Xiaohua
X
Han
Department of Neurosurgery, The Affiliated Hospital of Qingdao University Medical College, Qingdao, PR China.
Shaolei
S
Zhu
Department of Physiology, Qingdao University Medical College, Qingdao, PR China.
Bingxiang
B
Wang
Department of Physiology, Qingdao University Medical College, Qingdao, PR China.
Lei
L
Chen
Department of Physiology, Qingdao University Medical College, Qingdao, PR China.
Ran
R
Li
Department of Neurosurgery, The Affiliated Hospital of Qingdao University Medical College, Qingdao, PR China.
Weicheng
W
Yao
Department of Physiology, Qingdao University Medical College, Qingdao, PR China; Central Laboratory, The Affiliated Hospital of Qingdao University Medical College, Qingdao, PR China. Electronic address: zqu30033@yahoo.com.
Zhiqiang
Z
Qu
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D047309:Flavones / Q000494:pharmacology*; D006861:Hydrogen Peroxide / Q000494:pharmacology; D006892:Hydroxydopamines / Q000494:pharmacology*; D019636:Neurodegenerative Diseases / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D016716:PC12 Cells; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism
C485383:6,7-dihydroxyflavone; D000975:Antioxidants; D047309:Flavones; D006892:Hydroxydopamines; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide
1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; 6-Hydroxydopamine; 6-OHDA; 6-hydroxydopamine; 7,8-DHF; 7,8-Dihydroxyflavone; 7,8-dihydroxyflavone; AD; ANOVA; ATCC; Alzheimer’s disease; American type culture collection; Antioxidant; DA; DMEM; DMSO; Dulbecco’s modified Eagle’s medium; ECL; FCS; H(2)O(2); HRP; MDA; MPTP; MTT; Oxidative stress; PC12 cell; PD; Parkinson’s disease; ROS; Rh123; SDS; SOD; TH; TrkB; dimethyl sulfoxide; dopamine; enhanced chemiluminescence; fetal calf serum; horseradish peroxidase; hydrogen peroxide; malondialdehyde; one-way analysis of variance; p-H2A.X; phospho-histone H2A.X; reactive oxygen species; rhodamine 123; sodium dodecyl sulfate; superoxide dismutase; thiazolyl blue tetrazolium bromide; tyrosine hydroxylase; tyrosine kinase receptor B