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http://purl.uniprot.org/citations/24445604http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/24445604http://www.w3.org/2000/01/rdf-schema#comment"

Aim

Autophagic flux is an important process during autophagy maturation in smooth muscle cells. However, the molecular mechanisms underlying autophagic flux in these cells are largely unknown. Here, we revealed a previously undefined role of CD38, an enzyme that metabolizes NADP(+) into NAADP, in the regulation of autophagic flux in coronary arterial myocytes (CAMs).

Methods and results

In vivo CD38 gene knockout mice (CD38(-/-)) fed the high-fat Western diet showed increased accumulation of autophagosomes in coronary arterial media compared with that in wild-type (CD38(+/+)) mice, suggesting that CD38 gene deletion results in a defective autophagic process in CAMs of coronary arteries. In primary cultured CAMs, CD38 gene deletion markedly enhanced 7-ketocholesterol (7-Ket, an atherogenic stimulus and autophagy inducer)-induced accumulation of autophagosomes and increased expression of an autophagic marker, LC3B. However, no difference in autophagosome formation was observed between CD38(+/+) and CD38(-/-) CAMs when autophagic flux was blocked, which indicates that CD38 regulates autophagic flux rather than induction of autophagosome formation. Further, 7-Ket-induced formation of autophagolysosomes was markedly attenuated in CD38(-/-) CAMs compared with CD38(+/+) CAMs. Mechanistically, CD38 gene deletion markedly inhibited 7-Ket-induced dynein activation and autophagosome trafficking, which were associated with attenuated lysosomal Ca(2+) release. Importantly, coronary arterial smooth muscle from CD38(-/-) mice fed the Western diet exhibited phenotypic changes towards a more dedifferentiated state with abnormal extracellular matrix metabolism.

Conclusion

Taken together, these results suggest that CD38 plays a critical role in autophagosome trafficking and fusion with lysosomes, thus controlling autophagic flux in CAMs under atherogenic stimulation."xsd:string
http://purl.uniprot.org/citations/24445604http://purl.org/dc/terms/identifier"doi:10.1093/cvr/cvu011"xsd:string
http://purl.uniprot.org/citations/24445604http://purl.uniprot.org/core/author"Li X."xsd:string
http://purl.uniprot.org/citations/24445604http://purl.uniprot.org/core/author"Xu M."xsd:string
http://purl.uniprot.org/citations/24445604http://purl.uniprot.org/core/author"Zhang Y."xsd:string
http://purl.uniprot.org/citations/24445604http://purl.uniprot.org/core/author"Wang M."xsd:string
http://purl.uniprot.org/citations/24445604http://purl.uniprot.org/core/author"Xia M."xsd:string
http://purl.uniprot.org/citations/24445604http://purl.uniprot.org/core/author"Gulbins E."xsd:string
http://purl.uniprot.org/citations/24445604http://purl.uniprot.org/core/author"Li P.L."xsd:string
http://purl.uniprot.org/citations/24445604http://purl.uniprot.org/core/author"Boini K.M."xsd:string
http://purl.uniprot.org/citations/24445604http://purl.uniprot.org/core/author"Ratz P.H."xsd:string
http://purl.uniprot.org/citations/24445604http://purl.uniprot.org/core/date"2014"xsd:gYear
http://purl.uniprot.org/citations/24445604http://purl.uniprot.org/core/name"Cardiovasc Res"xsd:string
http://purl.uniprot.org/citations/24445604http://purl.uniprot.org/core/pages"68-78"xsd:string
http://purl.uniprot.org/citations/24445604http://purl.uniprot.org/core/title"Defective autophagosome trafficking contributes to impaired autophagic flux in coronary arterial myocytes lacking CD38 gene."xsd:string
http://purl.uniprot.org/citations/24445604http://purl.uniprot.org/core/volume"102"xsd:string
http://purl.uniprot.org/citations/24445604http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/24445604
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http://purl.uniprot.org/uniprot/#_P56528-mappedCitation-24445604http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/24445604
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http://purl.uniprot.org/uniprot/P56528http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/24445604
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