Expression of the MDR-1 gene-encoded P-glycoprotein in cardiomyocytes of conscious sheep undergoing acute myocardial ischemia followed by reperfusion.
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.
Laguens
Rubén P
RP
Department of Pathology, Favaloro University, Solís 453, 1078 Buenos Aires, Argentina.
Lazarowski
Alberto J
AJ
Cuniberti
Luis A
LA
Vera Janavel
Gustavo L
GL
Cabeza Meckert
Patricia M
PM
Yannarelli
Gustavo G
GG
del Valle
Héctor F
HF
Lascano
Elena C
EC
Negroni
Jorge A
JA
Crottogini
Alberto J
AJ
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
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D012333:RNA, Messenger