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Article: Stimulation of non-amyloidogenic processing of amyloid-β protein precursor by cryptotanshinone involves activation and translocation of ADAM10 and PKC-α

TitleStimulation of non-amyloidogenic processing of amyloid-β protein precursor by cryptotanshinone involves activation and translocation of ADAM10 and PKC-α
Authors
KeywordsADAM10
Alzheimer's disease
amyloid-β
Chinese medicine
cryptotanshinone
neuroblastoma
PKC
Issue Date2011
PublisherI O S Press. The Journal's web site is located at http://www.iospress.nl/html/13872877.php
Citation
Journal Of Alzheimer's Disease, 2011, v. 25 n. 2, p. 245-262 How to Cite?
AbstractCerebral deposition of amyloid-β peptide (Aβ) plaques is now considered the central feature of Alzheimer's disease. Recent studies suggest that cryptotanshinone (CTS) extracted from the root of Salvia miltiorrhiza Bunge could be used for the prevention and treatment of Alzheimer's disease. In this study, we investigated the role of CTS on non-amyloidogenic processing of amyloid-β protein precursor (AβPP) as well as its regulation by protein kinase C (PKC). Treatment with CTS dose-dependently and significantly reduced both intracellular and secreted levels of Aβ40 and Aβ42 in N2a mouse neuroblastoma cells stably expressing human SwedishAβPP (N2a-SwedAβPP). Using N2a-SwedAβPP and human neuroblastoma SHSY5Y cells, it was demonstrated that CTS significantly and dose-dependently increased the production of sAβPPα and C-terminal fragment-α (CTF-α) from AβPP. At the same time, CTS specifically increased the maturation of "a disintegrin and metalloproteinase-10" (ADAM10), an α-secretase candidate. The increase of sAβPPα secretion by CTS was blocked by the hydroxamate-based inhibitors GI254023X and GW280264X, and by the PKC-α inhibitor GÖ6976, suggesting involvement of the ADAM10 and PKC-α in CTS-induced α-secretase cleavage. In other experiments, CTS induced the phosphorylation of PKC-α indicating that PKC-α is involved in CTS-induced sAβPPα secretion. Furthermore, treatment of neuroblastoma cells with CTS induced the co-translocation of ADAM10 and PKC-α to the cell membrane, the site at which AβPP was cleaved, and this translocation was significantly reduced by GÖ6976. These results suggest that CTS-induced sAβPPα secretion is regulated by a PKC-α and ADAM10 cascade in neuroblastoma cells and may be involved in the lowering of Aβ production. © 2011 - IOS Press and the authors. All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/137189
ISSN
2015 Impact Factor: 3.92
2015 SCImago Journal Rankings: 1.774
ISI Accession Number ID
Funding AgencyGrant Number
Hong Kong Baptist UniversityFRG-II/08-09/19
FRG-I/09-10/22
RGC
Eu Yan Sang (Hong Kong) LimitedEYS/07-08/01
Lions Club of South Kowloon
Funding Information:

The study was supported by research grants FRG-II/08-09/19 and FRG-I/09-10/22 from Hong Kong Baptist University to Dr. M. Li, and by RGC GRF grants to Dr. J.D. Huang. It was partly supported by grant EYS/07-08/01 from Eu Yan Sang (Hong Kong) Limited. We especially thank Ms. Pui-Chun Lam, Ms. Wai-Sheung Chan and the Lions Club of South Kowloon, H. K. for their further financial support of this study. We would also like to thank Dr. Martha Dahlen for her critical review and revision.

References

 

DC FieldValueLanguage
dc.contributor.authorDurairajan, SSKen_HK
dc.contributor.authorLiu, LFen_HK
dc.contributor.authorLu, JHen_HK
dc.contributor.authorKoo, Ien_HK
dc.contributor.authorMaruyama, Ken_HK
dc.contributor.authorChung, SKen_HK
dc.contributor.authorHuang, JDen_HK
dc.contributor.authorLi, Men_HK
dc.date.accessioned2011-08-26T14:18:25Z-
dc.date.available2011-08-26T14:18:25Z-
dc.date.issued2011en_HK
dc.identifier.citationJournal Of Alzheimer's Disease, 2011, v. 25 n. 2, p. 245-262en_HK
dc.identifier.issn1387-2877en_HK
dc.identifier.urihttp://hdl.handle.net/10722/137189-
dc.description.abstractCerebral deposition of amyloid-β peptide (Aβ) plaques is now considered the central feature of Alzheimer's disease. Recent studies suggest that cryptotanshinone (CTS) extracted from the root of Salvia miltiorrhiza Bunge could be used for the prevention and treatment of Alzheimer's disease. In this study, we investigated the role of CTS on non-amyloidogenic processing of amyloid-β protein precursor (AβPP) as well as its regulation by protein kinase C (PKC). Treatment with CTS dose-dependently and significantly reduced both intracellular and secreted levels of Aβ40 and Aβ42 in N2a mouse neuroblastoma cells stably expressing human SwedishAβPP (N2a-SwedAβPP). Using N2a-SwedAβPP and human neuroblastoma SHSY5Y cells, it was demonstrated that CTS significantly and dose-dependently increased the production of sAβPPα and C-terminal fragment-α (CTF-α) from AβPP. At the same time, CTS specifically increased the maturation of "a disintegrin and metalloproteinase-10" (ADAM10), an α-secretase candidate. The increase of sAβPPα secretion by CTS was blocked by the hydroxamate-based inhibitors GI254023X and GW280264X, and by the PKC-α inhibitor GÖ6976, suggesting involvement of the ADAM10 and PKC-α in CTS-induced α-secretase cleavage. In other experiments, CTS induced the phosphorylation of PKC-α indicating that PKC-α is involved in CTS-induced sAβPPα secretion. Furthermore, treatment of neuroblastoma cells with CTS induced the co-translocation of ADAM10 and PKC-α to the cell membrane, the site at which AβPP was cleaved, and this translocation was significantly reduced by GÖ6976. These results suggest that CTS-induced sAβPPα secretion is regulated by a PKC-α and ADAM10 cascade in neuroblastoma cells and may be involved in the lowering of Aβ production. © 2011 - IOS Press and the authors. All rights reserved.en_HK
dc.languageengen_US
dc.publisherI O S Press. The Journal's web site is located at http://www.iospress.nl/html/13872877.phpen_HK
dc.relation.ispartofJournal of Alzheimer's Diseaseen_HK
dc.subjectADAM10en_HK
dc.subjectAlzheimer's diseaseen_HK
dc.subjectamyloid-βen_HK
dc.subjectChinese medicineen_HK
dc.subjectcryptotanshinoneen_HK
dc.subjectneuroblastomaen_HK
dc.subjectPKCen_HK
dc.titleStimulation of non-amyloidogenic processing of amyloid-β protein precursor by cryptotanshinone involves activation and translocation of ADAM10 and PKC-αen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=1387-2877&volume=25&issue=2&spage=245&epage=262&date=2011&atitle=Stimulation+of+non-amyloidogenic+processing+of+amyloid-β+protein+precursor+by+cryptotanshinone+involves+activation+and+translocation+of+ADAM10+and+PKC-α-
dc.identifier.emailChung, SK:skchung@hkucc.hku.hken_HK
dc.identifier.emailHuang, JD:jdhuang@hkucc.hku.hken_HK
dc.identifier.authorityChung, SK=rp00381en_HK
dc.identifier.authorityHuang, JD=rp00451en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.3233/JAD-2011-102085en_HK
dc.identifier.pmid21403388-
dc.identifier.scopuseid_2-s2.0-79960706730en_HK
dc.identifier.hkuros189410en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-79960706730&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume25en_HK
dc.identifier.issue2en_HK
dc.identifier.spage245en_HK
dc.identifier.epage262en_HK
dc.identifier.isiWOS:000293378300007-
dc.publisher.placeNetherlandsen_HK
dc.identifier.scopusauthoridDurairajan, SSK=23469201000en_HK
dc.identifier.scopusauthoridLiu, LF=40561366800en_HK
dc.identifier.scopusauthoridLu, JH=36917350900en_HK
dc.identifier.scopusauthoridKoo, I=23469778400en_HK
dc.identifier.scopusauthoridMaruyama, K=35461259400en_HK
dc.identifier.scopusauthoridChung, SK=7404292976en_HK
dc.identifier.scopusauthoridHuang, JD=8108660600en_HK
dc.identifier.scopusauthoridLi, M=36071647500en_HK

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