title: Artemisinin conferred ERK mediated neuroprotection to PC12 cells and cortical neurons exposed to sodium nitroprusside-induced oxidative insult.
abstract: The production of nitric oxide (NO) is one of the primary mediators of ischemic damage, glutamate neurotoxicity and neurodegeneration and therefore inhibition of NO-induced neurotoxicity may be considered a therapeutic target for reducing neuronal cell death (neuroprotection). In this study, artemisinin, a well-known anti-malaria drug was found to suppress sodium nitroprusside (SNP, a nitric oxide donor)-induced cell death in the PC12 cells and brain primary cortical neuronal cultures. Pretreatment of PC12 cells with artemisinin significantly suppressed SNP-induced cell death by decreasing the extent of oxidation, preventing the decline of mitochondrial membrane potential, restoring abnormal changes in nuclear morphology and reducing lactate dehydrogenase release and inhibiting caspase 3/7 activities. Western blotting analysis revealed that artemisinin was able to activate extracellular regulated protein kinases (ERK) pathway. Furthermore, the ERK inhibitor PD98059 blocked the neuroprotective effect of artemisinin whereas the PI3K inhibitor LY294002 had no effect. Cumulatively these findings support the notion that artemisinin confers neuroprotection from SNP-induce neuronal cell death insult, a phenomenon coincidentally related to activation of ERK phosphorylation. This SNP-induced oxidative insult in PC12 cell culture model may be useful to investigate molecular mechanisms of NO-induced neurotoxicity and drug-induced neuroprotection, and to generate novel therapeutic concepts for ischemic disease treatment.
authors.affiliation: Faculty of Health Sciences, University of Macau, Macau, China; State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China. Electronic address: wenhuazheng@umac.mo.
authors.forename: Wenhua
authors.initials: W
authors.lastname: Zheng
authors.affiliation: Faculty of Health Sciences, University of Macau, Macau, China.
authors.forename: Cheong-Meng
authors.initials: CM
authors.lastname: Chong
authors.affiliation: Faculty of Health Sciences, University of Macau, Macau, China.
authors.forename: Haitao
authors.initials: H
authors.lastname: Wang
authors.affiliation: Faculty of Health Sciences, University of Macau, Macau, China.
authors.forename: Xuanhe
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Faculty of Health Sciences, University of Macau, Macau, China; State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.
authors.forename: Lang
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Faculty of Health Sciences, University of Macau, Macau, China; State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.
authors.forename: Rikang
authors.initials: R
authors.lastname: Wang
authors.affiliation: Faculty of Health Sciences, University of Macau, Macau, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Meng
authors.affiliation: School of Pharmacy Institute for Drug Research, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 91102, Israel.
authors.forename: Philip
authors.initials: P
authors.lastname: Lazarovici
authors.affiliation: Faculty of Health Sciences, University of Macau, Macau, China.
authors.forename: Jiankang
authors.initials: J
authors.lastname: Fang
mesh_terms: D000818:Animals; D037621:Artemisinins / Q000008:administration & dosage*; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002867:Chromones / Q000008:administration & dosage; D005419:Flavonoids / Q000008:administration & dosage; D020935:MAP Kinase Signaling System / Q000187:drug effects; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D009025:Morpholines / Q000008:administration & dosage; D009410:Nerve Degeneration / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000187:drug effects* / Q000473:pathology; D000066829:Neuroprotection / Q000187:drug effects; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000378:metabolism; D009599:Nitroprusside / Q000633:toxicity; D018384:Oxidative Stress / Q000187:drug effects*; D016716:PC12 Cells; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D037621:Artemisinins; D002867:Chromones; D005419:Flavonoids; D009025:Morpholines; D020030:Nitric Oxide Donors; D000081082:Phosphoinositide-3 Kinase Inhibitors; D009599:Nitroprusside; D009569:Nitric Oxide; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C031327:artemisinin; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one
keywords: Artemisinin; ERK1/2; Neuroprotection; PC12 cells; Sodium nitroprusside