Apoptosis repressor with caspase recruitment domain is dramatically reduced in cardiac, skeletal, and vascular smooth muscle during hypertension.
Apoptosis repressor with caspase recruitment domain (ARC) is a unique anti-apoptotic protein with a distinct tissue distribution. In addition, unlike most anti-apoptotic proteins which act on one pathway, ARC can inhibit apoptosis mediated by both the death-receptor and mitochondrial signaling pathways. In this study, we confirm previous reports showing high levels of ARC protein in rat heart and skeletal muscle, but demonstrate for the first time that ARC is also expressed in rat aorta. Immunoblot analysis on endothelium-denuded aorta as well as immunohistochemical analysis on intact aorta demonstrated that ARC was highly expressed in smooth muscle. Immunoblot analysis also found that ARC protein was severely downregulated in skeletal muscle (-82%; P<0.001), heart (-80%; P<0.001), and aorta (-71%; P<0.001) of spontaneously hypertensive rats (SHR) compared to normotensive Wistar-Kyoto (WKY) rats. Decreased ARC levels were also confirmed in tissues of hypertensive animals by immunohistochemical analysis. Collectively, this data suggests that ARC protein is expressed in vascular smooth muscle and is significantly reduced in several target tissues during hypertension.
Quadrilatero
Joe
J
Department of Kinesiology, University of Waterloo, Waterloo, Ontario, Canada N2L3G1. jquadril@uwaterloo.ca
Bloemberg
Darin
D
D000818:Animals; D001011:Aorta / Q000201:enzymology / Q000378:metabolism*; D051017:Apoptosis Regulatory Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D053468:CARD Signaling Adaptor Proteins / Q000037:antagonists & inhibitors*; D020169:Caspases; D015536:Down-Regulation; D006973:Hypertension / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D009124:Muscle Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D018482:Muscle, Skeletal / Q000201:enzymology / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000201:enzymology / Q000378:metabolism*; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017207:Rats, Sprague-Dawley
D051017:Apoptosis Regulatory Proteins; D053468:CARD Signaling Adaptor Proteins; D009124:Muscle Proteins; C491788:Nol3 protein, rat; D020169:Caspases