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Neurochem Int. 2014 Jan;64:18-23. doi: 10.1016/j.neuint.2013.10.018. Epub 2013 Nov 9.

Antioxidant action of 7,8-dihydroxyflavone protects PC12 cells against 6-hydroxydopamine-induced cytotoxicity.

Author information

1
Department of Physiology, Qingdao University Medical College, Qingdao, PR China. Electronic address: xiaohua.han@163.com.
2
Department of Neurosurgery, The Affiliated Hospital of Qingdao University Medical College, Qingdao, PR China.
3
Department of Physiology, Qingdao University Medical College, Qingdao, PR China.
4
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.

Abstract

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.

KEYWORDS:

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

PMID:
24220540
DOI:
10.1016/j.neuint.2013.10.018
[Indexed for MEDLINE]

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