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Article: Sunitinib Produces Neuroprotective Effect Via Inhibiting Nitric Oxide Overproduction

TitleSunitinib Produces Neuroprotective Effect Via Inhibiting Nitric Oxide Overproduction
Authors
Issue Date2014
PublisherWiley-Blackwell Publishing Ltd..
Citation
CNS Neuroscience and Therapeutics, 2014, v. 20 n. 3, p. 244-252 How to Cite?
AbstractBACKGROUND: Sunitinib is an inhibitor of the multiple receptor tyrosine kinases (RTKs) for cancer therapy. Some sunitinib analogues could prevent neuronal death induced by various neurotoxins. However, the neuroprotective effects of sunitinib have not been reported. METHODS: Cerebellar granule neurons (CGNs) and SH-SY5Y cells were exposed to low-potassium and MPP+ challenges, respectively. MTT assay, FDA/PI staining, Hoechst staining, DAF-FM, colorimetric nitric oxide synthase (NOS) activity assay, and Western blotting were applied to detect cell viability, NO production, NOS activity, and neuronal NOS (nNOS) expression. Short hairpin RNA was used to decrease nNOS expression. In vitro NOS enzyme activity assay was used to determine the direct inhibition of nNOS by sunitinib. RESULTS: Sunitinib prevented low-potassium-induced neuronal apoptosis in CGNs and MPP+ -induced neuronal death in SH-SY5Y cells. However, PTK787, another RTK inhibitor, failed to decrease neurotoxicity in the same models. Sunitinib reversed the increase in NO levels, NOS activity, and nNOS expression induced by low potassium or MPP+ . Knockdown of nNOS expression partially abolished the neuroprotective effects of sunitinib. Moreover, sunitinib directly inhibited nNOS enzyme activity. CONCLUSIONS: Sunitinib exerts its neuroprotective effects by inhibiting NO overproduction, possibly via the inhibition of nNOS activity and the decrease in nNOS expression.
Persistent Identifierhttp://hdl.handle.net/10722/195720
ISSN
2015 Impact Factor: 4.019
2015 SCImago Journal Rankings: 1.536
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorCui, Wen_US
dc.contributor.authorZhang, ZJen_US
dc.contributor.authorHu, SQen_US
dc.contributor.authorMak, SHen_US
dc.contributor.authorXu, DPen_US
dc.contributor.authorChoi, CLen_US
dc.contributor.authorWang, YQen_US
dc.contributor.authorTsim, WKen_US
dc.contributor.authorLee, MYen_US
dc.contributor.authorRong, Jen_US
dc.contributor.authorHan, YFen_US
dc.date.accessioned2014-03-07T04:32:37Z-
dc.date.available2014-03-07T04:32:37Z-
dc.date.issued2014en_US
dc.identifier.citationCNS Neuroscience and Therapeutics, 2014, v. 20 n. 3, p. 244-252en_US
dc.identifier.issn1755-5930-
dc.identifier.urihttp://hdl.handle.net/10722/195720-
dc.description.abstractBACKGROUND: Sunitinib is an inhibitor of the multiple receptor tyrosine kinases (RTKs) for cancer therapy. Some sunitinib analogues could prevent neuronal death induced by various neurotoxins. However, the neuroprotective effects of sunitinib have not been reported. METHODS: Cerebellar granule neurons (CGNs) and SH-SY5Y cells were exposed to low-potassium and MPP+ challenges, respectively. MTT assay, FDA/PI staining, Hoechst staining, DAF-FM, colorimetric nitric oxide synthase (NOS) activity assay, and Western blotting were applied to detect cell viability, NO production, NOS activity, and neuronal NOS (nNOS) expression. Short hairpin RNA was used to decrease nNOS expression. In vitro NOS enzyme activity assay was used to determine the direct inhibition of nNOS by sunitinib. RESULTS: Sunitinib prevented low-potassium-induced neuronal apoptosis in CGNs and MPP+ -induced neuronal death in SH-SY5Y cells. However, PTK787, another RTK inhibitor, failed to decrease neurotoxicity in the same models. Sunitinib reversed the increase in NO levels, NOS activity, and nNOS expression induced by low potassium or MPP+ . Knockdown of nNOS expression partially abolished the neuroprotective effects of sunitinib. Moreover, sunitinib directly inhibited nNOS enzyme activity. CONCLUSIONS: Sunitinib exerts its neuroprotective effects by inhibiting NO overproduction, possibly via the inhibition of nNOS activity and the decrease in nNOS expression.en_US
dc.languageengen_US
dc.publisherWiley-Blackwell Publishing Ltd..-
dc.relation.ispartofCNS Neuroscience and Therapeuticsen_US
dc.rightsThe definitive version is available at www3.interscience.wiley.com-
dc.titleSunitinib Produces Neuroprotective Effect Via Inhibiting Nitric Oxide Overproductionen_US
dc.typeArticleen_US
dc.identifier.emailRong, J: jrong@hku.hken_US
dc.identifier.authorityRong, J=rp00515en_US
dc.identifier.doi10.1111/cns.12203-
dc.identifier.pmid24393200-
dc.identifier.hkuros228242en_US
dc.identifier.volume20en_US
dc.identifier.issue3en_US
dc.identifier.spage244en_US
dc.identifier.epage252en_US
dc.identifier.isiWOS:000331540800007-
dc.publisher.placeUnited Kingdom-

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