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Article: Mitochondrial uncoupling protein-2 (UCP2) mediates leptin protection against MPP+ toxicity in neuronal cells

TitleMitochondrial uncoupling protein-2 (UCP2) mediates leptin protection against MPP+ toxicity in neuronal cells
Authors
Ho, PWLiu, HFHo, JWZhang, WYChu, ACKwok, KHGe, XChan, KHRamsden, DBHo, SL
Issue Date2010
PublisherSpringer New York LLC. The Journal's web site is located at http://www.springerlink.com/content/1029-8428
Citation
Neurotoxicity Research, 2010, v. 17 n. 4, p. 332-343 How to Cite?
DOI: http://dx.doi.org/10.1007/s12640-009-9109-y
AbstractMitochondrial dysfunction is involved in the pathogenesis of neurodegenerative diseases, including Parkinson's disease (PD). Uncoupling proteins (UCPs) delink ATP production from biofuel oxidation in mitochondria to reduce oxidative stress. UCP2 is expressed in brain, and has neuroprotective effects under various toxic insults. We observed induction of UCP2 expression by leptin in neuronal cultures, and hypothesize that leptin may preserve neuronal survival via UCP2. We showed that leptin preserved cell survival in neuronal SH-SY5Y cells against MPP+ toxicity (widely used in experimental Parkinsonian models) by maintaining ATP levels and mitochondrial membrane potential (MMP); these effects were accompanied by increased UCP2 expression. Leptin had no effect in modulating reactive oxygen species levels. Stable knockdown of UCP2 expression reduced ATP levels, and abolished leptin protection against MPP+-induced mitochondrial depolarization, ATP deficiency, and cell death, indicating that UCP2 is critical in mediating these neuroprotective effects of leptin against MPP+ toxicity. Interestingly, UCP2 knockdown increased UCP4 expression, but not of UCP5. Our findings show that leptin preserves cell survival by maintaining MMP and ATP levels mediated through UCP2 in MPP+-induced toxicity.
Persistent Identifierhttp://hdl.handle.net/10722/124030
ISSN
1476-3524
2023 Impact Factor: 2.9
2023 SCImago Journal Rankings: 0.789
PubMed Central ID
PMC2946553
ISI Accession Number ID
WOS:000278028300003
Funding AgencyGrant Number
Henry G Leong Professorship in Neurology
Research Grants Council, Hong Kong (HKU)7661/07M
200707176087
Donation Fund for Neurology Research (SLH)
University of Hong Kong
Funding Information:

We gratefully acknowledge the invaluable support from the Henry G Leong Professorship in Neurology (SLH), the Research Grants Council, Hong Kong (HKU 7661/07M; SLH), the Donation Fund for Neurology Research (SLH), and the Small Project Funding (HKU 200707176087; PWLH). PWL Ho is supported by a Research Assistant Professorship; WY Zhang is supported by a Postdoctoral Fellowship; HF Liu, X Ge, and JWM Ho are supported by PhD Studentships from the University of Hong Kong. KHH Kwok PhD studentship was fully supported by the Donation Fund for Neurology Research (SLH).

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Grants
Metabolic regulation of leptin on neuronal mitochondrial uncoupling: implication for neuroprotection in Parkinsonism

 

DC FieldValueLanguage
dc.contributor.authorHo, PWen_HK
dc.contributor.authorLiu, HFen_HK
dc.contributor.authorHo, JWen_HK
dc.contributor.authorZhang, WYen_HK
dc.contributor.authorChu, ACen_HK
dc.contributor.authorKwok, KHen_HK
dc.contributor.authorGe, Xen_HK
dc.contributor.authorChan, KHen_HK
dc.contributor.authorRamsden, DBen_HK
dc.contributor.authorHo, SLen_HK
dc.date.accessioned2010-10-19T04:34:24Z-
dc.date.available2010-10-19T04:34:24Z-
dc.date.issued2010en_HK
dc.identifier.citationNeurotoxicity Research, 2010, v. 17 n. 4, p. 332-343en_HK
dc.identifier.issn1476-3524en_HK
dc.identifier.urihttp://hdl.handle.net/10722/124030-
dc.description.abstractMitochondrial dysfunction is involved in the pathogenesis of neurodegenerative diseases, including Parkinson's disease (PD). Uncoupling proteins (UCPs) delink ATP production from biofuel oxidation in mitochondria to reduce oxidative stress. UCP2 is expressed in brain, and has neuroprotective effects under various toxic insults. We observed induction of UCP2 expression by leptin in neuronal cultures, and hypothesize that leptin may preserve neuronal survival via UCP2. We showed that leptin preserved cell survival in neuronal SH-SY5Y cells against MPP+ toxicity (widely used in experimental Parkinsonian models) by maintaining ATP levels and mitochondrial membrane potential (MMP); these effects were accompanied by increased UCP2 expression. Leptin had no effect in modulating reactive oxygen species levels. Stable knockdown of UCP2 expression reduced ATP levels, and abolished leptin protection against MPP+-induced mitochondrial depolarization, ATP deficiency, and cell death, indicating that UCP2 is critical in mediating these neuroprotective effects of leptin against MPP+ toxicity. Interestingly, UCP2 knockdown increased UCP4 expression, but not of UCP5. Our findings show that leptin preserves cell survival by maintaining MMP and ATP levels mediated through UCP2 in MPP+-induced toxicity.en_HK
dc.languageengen_HK
dc.publisherSpringer New York LLC. The Journal's web site is located at http://www.springerlink.com/content/1029-8428en_HK
dc.relation.ispartofNeurotoxicity researchen_HK
dc.subject.meshHerbicides - toxicityen_HK
dc.subject.meshIon Channels - genetics - physiologyen_HK
dc.subject.meshLeptin - pharmacologyen_HK
dc.subject.meshMitochondrial Proteins - genetics - physiologyen_HK
dc.subject.meshNeuroprotective Agents - pharmacologyen_HK
dc.titleMitochondrial uncoupling protein-2 (UCP2) mediates leptin protection against MPP+ toxicity in neuronal cellsen_HK
dc.typeArticleen_HK
dc.identifier.emailHo, PW: hwl2002@hku.hken_HK
dc.identifier.emailChu, AC: bcccy@hkucc.hku.hken_HK
dc.identifier.emailHo, SL: slho@hku.hken_HK
dc.identifier.authorityHo, PW=rp00259en_HK
dc.identifier.authorityChu, AC=rp00505en_HK
dc.identifier.authorityHo, SL=rp00240en_HK
dc.description.naturelink_to_OA_fulltexten_HK
dc.identifier.doi10.1007/s12640-009-9109-yen_HK
dc.identifier.pmid19763737-
dc.identifier.pmcidPMC2946553en_HK
dc.identifier.scopuseid_2-s2.0-77953941374en_HK
dc.identifier.hkuros169291en_HK
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dc.identifier.volume17en_HK
dc.identifier.issue4en_HK
dc.identifier.spage332en_HK
dc.identifier.epage343en_HK
dc.identifier.eissn1476-3524en_HK
dc.identifier.isiWOS:000278028300003-
dc.description.otherSpringer Open Choice, 01 Dec 2010-
dc.relation.projectMetabolic regulation of leptin on neuronal mitochondrial uncoupling: implication for neuroprotection in Parkinsonism-
dc.identifier.scopusauthoridHo, PW=25027612100en_HK
dc.identifier.scopusauthoridLiu, HF=27170235100en_HK
dc.identifier.scopusauthoridHo, JW=8685214100en_HK
dc.identifier.scopusauthoridZhang, WY=7409424869en_HK
dc.identifier.scopusauthoridChu, AC=24343085700en_HK
dc.identifier.scopusauthoridKwok, KH=7102194193en_HK
dc.identifier.scopusauthoridGe, X=34876539700en_HK
dc.identifier.scopusauthoridChan, KH=7406034963en_HK
dc.identifier.scopusauthoridRamsden, DB=7102612805en_HK
dc.identifier.scopusauthoridHo, SL=25959633500en_HK
dc.identifier.issnl1029-8428-

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