Gene expression profile of mouse myocardium with transgenic overexpression of A1 adenosine receptors.
Transgenic mice with cardiac-specific overexpression of adenosine A(1) receptors (A(1)AR) have demonstrated metabolic and functional tolerance to myocardial ischemia. We utilized cDNA microarrays to test the hypothesis that the cardioprotective mechanism(s) of A(1) overexpression involves altered gene expression. Total RNA extracted from the left ventricles from A(1) transgenic (n = 4) and wild-type (n = 6) mice was hybridized to Affymetrix mgU74A chips. Comparison of RNA expression levels in transgenic to wild-type myocardium revealed approximately 636 known genes with expression significantly altered by greater than 25%. We observed increased expressions of genes including NADH dehydrogenase, the GLUT4 glucose transporter, Na-K-ATPase, sarcolemmal K(ATP) channels, and Bcl-xl in A(1)AR-overexpressing hearts. We also observed decreased expression of pro-apoptotic genes including a 50% reduction in message level of caspase-8. Protein expression of GLUT4 and caspase-8 was also altered comparable to the differences in gene expression. These data illustrate genes with chronically altered patterns of expression in A(1) transgenic mouse myocardium that may be related to adenosine receptor overexpression-mediated cardioprotection.
Lankford
Amy R
AR
Department of Pediatrics and Cardiovascular Research Center, University of Virginia Health System, Charlottesville Virginia 22908, USA. arl2b@virginia.edu
Byford
Anne M
AM
Ashton
Kevin J
KJ
French
Brent A
BA
Lee
Jae K
JK
Headrick
John P
JP
Matherne
G Paul
GP
D000255:Adenosine Triphosphate / Q000235:genetics / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases / Q000096:biosynthesis; D020869:Gene Expression Profiling / Q000379:methods*; D005786:Gene Expression Regulation / Q000235:genetics*; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics; D005796:Genes / Q000235:genetics; D005809:Genes, Regulator / Q000235:genetics; D051275:Glucose Transporter Type 4; D006352:Heart Ventricles / Q000737:chemistry / Q000378:metabolism; D007249:Inflammation / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009004:Monosaccharide Transport Proteins / Q000235:genetics; D009124:Muscle Proteins; D009206:Myocardium / Q000737:chemistry* / Q000201:enzymology / Q000378:metabolism*; D009245:NADH Dehydrogenase / Q000235:genetics; D009569:Nitric Oxide / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000096:biosynthesis; D018047:Receptors, Purinergic P1 / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D015398:Signal Transduction / Q000235:genetics; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics; D012984:Software / Q000592:standards; D020257:Ventricular Remodeling / Q000235:genetics
D051275:Glucose Transporter Type 4; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D012333:RNA, Messenger; D018047:Receptors, Purinergic P1; C495693:Slc2a4 protein, mouse; D009569:Nitric Oxide; D000255:Adenosine Triphosphate; D009245:NADH Dehydrogenase; C505526:Casp8 protein, mouse; C506434:Casp9 protein, mouse; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases; D000254:Sodium-Potassium-Exchanging ATPase