title: Secalonic acid A protects dopaminergic neurons from 1-methyl-4-phenylpyridinium (MPP⁺)-induced cell death via the mitochondrial apoptotic pathway.
abstract: Secalonic acid A (SAA) is a natural compound found in marine fungi. We have reported that SAA can attenuate the cytotoxicity of colchicine in rat cortical neurons. Whether SAA can also inhibit the neurotoxicity of 1-methyl-4-phenylpyridinium (MPP(+)) in dopaminergic neurons has not been investigated. Here, we show that pretreatment with 1 μM SAA significantly rescued tyrosine hydroxylase (TH)-positive neurons from MPP(+)-induced neurotoxicity in primary dopaminergic neuron culture. Moreover, SAA at doses of 0.15 mg/kg and 0.75 mg/kg increased the number of dopaminergic neurons and upregulated striatal dopamine in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease mice experiments. We also show that SAA significantly attenuated cytotoxicity induced by 2.5 mM MPP(+) in SH-SY5Y cells. These results indicate that the activation of JNK, p38 mitogen activated protein kinase (MAPK) and caspase-3 during apoptosis triggered by MPP(+) could be suppressed by SAA; on the other hand, an MPP(+)-induced increase in the expression of Bax in SH-SY5Y cells was blocked by SAA. These results indicate that inhibition of the phosphorylation of JNK and p38 MAPK, down-regulation of Bax expression, and suppression of caspase-3 activation are involved in the protective effects of SAA against MPP(+) toxicity in SH-SY5Y cells. SAA may rescue dopaminergic neurons from MPP(+)-induced cell death through the mitochondrial apoptotic pathway.
authors.affiliation: Institute of Health and Environmental Medicine, Academy of Military Medical Science, 27 Taiping Road, Beijing 100850, PR China.
authors.forename: Aifeng
authors.initials: A
authors.lastname: Zhai
authors.forename: Xiaonan
authors.initials: X
authors.lastname: Zhu
authors.forename: Xuelan
authors.initials: X
authors.lastname: Wang
authors.forename: Ruzhu
authors.initials: R
authors.lastname: Chen
authors.forename: Hai
authors.initials: H
authors.lastname: Wang
mesh_terms: D015655:1-Methyl-4-phenylpyridinium / Q000633:toxicity*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D059290:Dopaminergic Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005260:Female; D020267:MPTP Poisoning / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D008297:Male; D008636:Mesencephalon / Q000166:cytology / Q000196:embryology; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D011247:Pregnancy; D061251:Primary Cell Culture; D051381:Rats; D017207:Rats, Sprague-Dawley; D013378:Substantia Nigra / Q000166:cytology; D044004:Xanthones / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D018696:Neuroprotective Agents; D044004:Xanthones; C009218:secalonic acid; D015655:1-Methyl-4-phenylpyridinium