Attenuated cardiovascular hypertrophy and oxidant generation in response to angiotensin II infusion in glutaredoxin-1 knockout mice.
Glutaredoxin-1 (Glrx) is a thioltransferase that regulates protein S-glutathiolation. To elucidate the role of endogenous Glrx in cardiovascular disease, Glrx knockout (KO) mice were infused with angiotensin II (Ang II) for 6days. After Ang II infusion, body weight and blood pressure were similar between WT and Glrx KO mice. However, compared to WT mice, Glrx KO mice demonstrated (1) less cardiac and aortic medial hypertrophy, (2) less oxidant generation in aorta as assessed by dihydroethidium staining and nitrotyrosine, (3) decreased phosphorylation of Akt in the heart, and (4) less expression of inducible NOS in aorta and heart. In cultured embryonic fibroblasts from Glrx KO mice, S-glutathiolation of actin was enhanced and actin depolymerization was impaired after hydrogen peroxide stimulation compared with WT cells. Furthermore, oxidant generation in phorbol ester-stimulated fibroblasts and RAW 264.7 macrophage-like cells was lower with Glrx siRNA knockdown. These data indicate that Ang II-induced oxidant production and hypertrophic responses were attenuated in Glrx KO mice, which may result from impaired NADPH oxidase activation.
Bachschmid
Markus M
MM
Vascular Biology Unit, Department of Medicine, Boston University, Boston, MA 02118, USA.
Xu
Shanqin
S
Maitland-Toolan
Karlene A
KA
Ho
Ye-Shih
YS
Cohen
Richard A
RA
Matsui
Reiko
R
D008841:Actin Cytoskeleton / Q000378:metabolism; D000804:Angiotensin II / Q000008:administration & dosage; D000818:Animals; D001011:Aorta / Q000473:pathology*; D002318:Cardiovascular Diseases / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D002460:Cell Line; D054477:Glutaredoxins / Q000235:genetics / Q000378:metabolism*; D006984:Hypertrophy / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D007260:Infusion Pumps; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009206:Myocardium / Q000473:pathology*; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis / Q000235:genetics; D051058:Oncogene Protein v-akt / Q000235:genetics / Q000378:metabolism; D016877:Oxidants / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
C516006:Glrx protein, mouse; D054477:Glutaredoxins; D016877:Oxidants; D034741:RNA, Small Interfering; D000804:Angiotensin II; C002744:3-nitrotyrosine; D014443:Tyrosine; D052247:Nitric Oxide Synthase Type II; D051058:Oncogene Protein v-akt