Mass-production of human ACAT-1 and ACAT-2 to screen isoform-specific inhibitor: a different substrate specificity and inhibitory regulation

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dc.contributor.authorKyung Hyun Cho-
dc.contributor.authorSo Jin An-
dc.contributor.authorWoo Song Lee-
dc.contributor.authorY K Paik-
dc.contributor.authorYoung Kook Kim-
dc.contributor.authorTae Sook Jeong-
dc.date.accessioned2017-04-19T09:00:18Z-
dc.date.available2017-04-19T09:00:18Z-
dc.date.issued2003-
dc.identifier.issn0006-291X-
dc.identifier.uri10.1016/j.bbrc.2003.08.077ko
dc.identifier.urihttps://oak.kribb.re.kr/handle/201005/6247-
dc.description.abstractRecently, acyl-CoA:cholesterol acyltransferase was found to be present as two isoforms, ACAT-1 and ACAT-2, in mammalian tissues with different metabolic functions and tissue-specific locations. In this study, the isoforms were mass-produced individually from insect cells to establish a more sensitive and reliable screening method for specific inhibitors against each isoform. The expressed hACAT-1 and hACAT-2 appeared as a 50kDa- and a 46kDa-band on SDS-PAGE, respectively, from Hi5 cells and they preferred to exist in oligomeric form, from dimer to tetramer, during the purification process. They also exhibited an approximate 3.4 to 3.7-fold increase in activities when compared to rat liver microsomal fractions at the same protein concentration. Known ACAT inhibitors, pyripyropene A, oleic acid anilide, and diethyl pyrocarbonate, were tested to evaluate the inhibitory specificity and sensitivity of the expressed enzymes. Interestingly, pyripyropene A inhibited only the hACAT-2 fraction with IC 50=0.64μM but not the hACAT-1 fraction; whereas the fatty acid anilide did not show a significant difference in inhibitory activity with either hACAT-1 or hACAT-2. Furthermore, cholesterol was more rapidly utilized by hACAT-1, but hACAT-2 esterified other cholic acid derivatives more efficiently. These results suggest that the specificity of each substrate and inhibitor was highly different, depending on each isoform from the viewpoint of the regulatory site and the substrate binding site location.-
dc.publisherElsevier-
dc.titleMass-production of human ACAT-1 and ACAT-2 to screen isoform-specific inhibitor: a different substrate specificity and inhibitory regulation-
dc.title.alternativeMass-production of human ACAT-1 and ACAT-2 to screen isoform-specific inhibitor: a different substrate specificity and inhibitory regulation-
dc.typeArticle-
dc.citation.titleBiochemical and Biophysical Research Communications-
dc.citation.number4-
dc.citation.endPage872-
dc.citation.startPage864-
dc.citation.volume309-
dc.contributor.affiliatedAuthorKyung Hyun Cho-
dc.contributor.affiliatedAuthorSo Jin An-
dc.contributor.affiliatedAuthorWoo Song Lee-
dc.contributor.affiliatedAuthorYoung Kook Kim-
dc.contributor.affiliatedAuthorTae Sook Jeong-
dc.contributor.alternativeName조경현-
dc.contributor.alternativeName안소진-
dc.contributor.alternativeName이우송-
dc.contributor.alternativeName백융기-
dc.contributor.alternativeName김영국-
dc.contributor.alternativeName정태숙-
dc.identifier.bibliographicCitationBiochemical and Biophysical Research Communications, vol. 309, no. 4, pp. 864-872-
dc.identifier.doi10.1016/j.bbrc.2003.08.077-
dc.subject.keywordAcyl-CoA:cholesterol acyltransferase-
dc.subject.keywordAtherosclerosis-
dc.subject.keywordHypercholesterolemia-
dc.subject.keywordIsoenzyme-
dc.subject.keywordSpecific inhibitors-
dc.subject.keywordViral expression-
dc.subject.localACAT (acyl-CoA: cholesterol acyltransferase)-
dc.subject.localAcyl-CoA:cholesterol acyltransferase (ACAT)-
dc.subject.localcholesterol acytransferase (ACAT)-
dc.subject.localCholestrol Acyl Transferase (ACAT)-
dc.subject.localAcyl CoA: cholesterol acyltransferase (ACAT)-
dc.subject.localACAT (Acyl-CoA:cholesterol acyltransferase)-
dc.subject.localAcyl-CoA:cholesterol acyltransferase-
dc.subject.localACAT-
dc.subject.localAcyl-CoA: cholesterol acyltransferase-
dc.subject.localacyl-CoA:cholesterol acyltransferase (ACAT)-
dc.subject.localAcyl-CoA: cholesterol acyltransferase (ACAT)-
dc.subject.localAcyl-coenzyme A: cholesterol acyltransferase (ACAT)-
dc.subject.localCholesterol acytransferase (ACAT)-
dc.subject.localcholestrol acyl transferase (ACAT)-
dc.subject.localatherosclerosis-
dc.subject.localAtherosclerosis-
dc.subject.localatheroclerosis-
dc.subject.localHypercholesterolemia-
dc.subject.localhypercholesterolemia-
dc.subject.localisoenzyme-
dc.subject.localIsoenzyme-
dc.subject.localSpecific inhibitors-
dc.subject.localViral expression-
dc.description.journalClassY-
Appears in Collections:
Jeonbuk Branch Institute > Functional Biomaterial Research Center > 1. Journal Articles
Division of Biomedical Research > Microbiome Convergence Research Center > 1. Journal Articles
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