title: Expression of the MDR-1 gene-encoded P-glycoprotein in cardiomyocytes of conscious sheep undergoing acute myocardial ischemia followed by reperfusion.
abstract: We have recently reported that in chronic myocardial ischemia, adult mammalian cardiomyocytes express P-glycoprotein (P-gp). We now investigate if P-gp is also expressed in acute regional ischemia followed by reperfusion. Adult conscious sheep underwent 12-min occlusion of the mid-left anterior descending artery (inflatable cuff). Successful ischemia-reperfusion was confirmed by monitoring percent systolic left ventricular anterior wall thickening (sonomicrometry) during the whole ischemic period and every 10 min over 2 hr following cuff deflation. At 3, 24, and 48 hr after reperfusion, P-gp expression was investigated by immunohistochemistry and Western blot and MDR-1 mRNA by RT-PCR. Cardiomyocytes in the occluded artery territory (but not those in remote areas) consistently expressed P-gp at their sarcolemma. Whereas at 3 and 24 hr P-gp was mainly observed in the T tubules, at 48 hr it predominated in intercalated discs and gap junctions. RT-PCR and Western blot revealed higher expression in ischemic than in control myocardium. We conclude that in adult sheep with acute myocardial ischemia, the MDR-1 gene-encoded P-gp is expressed at the sarcolemma of the cardiomyocytes from 3 hr up to at least 48 hr after reperfusion.
authors.affiliation: Department of Pathology, Favaloro University, Solís 453, 1078 Buenos Aires, Argentina.
authors.forename: Rubén P
authors.initials: RP
authors.lastname: Laguens
authors.forename: Alberto J
authors.initials: AJ
authors.lastname: Lazarowski
authors.forename: Luis A
authors.initials: LA
authors.lastname: Cuniberti
authors.forename: Gustavo L
authors.initials: GL
authors.lastname: Vera Janavel
authors.forename: Patricia M
authors.initials: PM
authors.lastname: Cabeza Meckert
authors.forename: Gustavo G
authors.initials: GG
authors.lastname: Yannarelli
authors.forename: Héctor F
authors.initials: HF
authors.lastname: del Valle
authors.forename: Elena C
authors.initials: EC
authors.lastname: Lascano
authors.forename: Jorge A
authors.initials: JA
authors.lastname: Negroni
authors.forename: Alberto J
authors.initials: AJ
authors.lastname: Crottogini
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis* / Q000235:genetics; D000818:Animals; D005260:Female; D019450:Genes, MDR; D017202:Myocardial Ischemia / Q000378:metabolism*; D015425:Myocardial Reperfusion; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000648:ultrastructure; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012756:Sheep; D013997:Time Factors
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D012333:RNA, Messenger