Tags

Type your tag names separated by a space and hit enter

Cys18-Cys137 disulfide bond in mouse angiotensinogen does not affect AngII-dependent functions in vivo.
Hypertension 2015; 65(4):800-5H

Abstract

Renin cleavage of angiotensinogen (AGT) releases angiotensin I (AngI) in the initial step of producing all angiotensin peptides. It has been suggested recently that redox regulation of a disulfide bond in AGT involving Cys18-Cys137 may be important to its renin cleavage efficiency in vivo. The purpose of this study was to test this prediction in a mouse model by comparing AngII production and AngII-dependent functions in mice expressing wild-type AGT versus a mutated form of AGT lacking the disulfide bond. Wild-type (hepAGT+/+) and hepatocyte-specific AGT-deficient (hepAGT-/-) littermates were developed in an low-density lipoprotein receptor -/- background. hepAGT+/+ mice were injected intraperitoneally with adeno-associated viral (AAV) vector containing a null insert. hepAGT-/- mice were injected with AAV containing a null insert, wild-type AGT or Cys18Ser and Cys137Ser mutated AGT. Two weeks after AAV injection, mice were fed a Western diet for 12 weeks. Administration of AAV containing either form of AGT led to similar plasma AGT concentrations in hepAGT-/- mice. High plasma renin concentrations in hepAGT-/- mice were suppressed equally by both forms of AGT, which were accompanied by comparable increases of plasma AngII concentrations similar to hepAGT+/+ mice. AAV-driven expression of both forms of AGT led to equivalent increases of systolic blood pressure and augmentation of atherosclerotic lesion size in hepAGT-/- mice. These measurements were comparable to systolic blood pressure and atherosclerotic lesions in hepAGT+/+ mice. These data indicate that the Cys18-Cys137 disulfide bond in AGT is dispensable for AngII production and AngII-dependent functions in mice.

Authors+Show Affiliations

From the Saha Cardiovascular Research Center (C.W., Y.X., H.L., D.A.H., A.B., J.J.M., A.D.), Department of Pharmacology and Nutritional Sciences (C.W., L.A.C., A.D.), and Department of Molecular and Cellular Biochemistry (C.W.V.K.), University of Kentucky, Lexington; and The Cardiovascular Key Lab of Zhejiang Province, Department of Cardiology, the Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China (Y.X., J.-a.W.).From the Saha Cardiovascular Research Center (C.W., Y.X., H.L., D.A.H., A.B., J.J.M., A.D.), Department of Pharmacology and Nutritional Sciences (C.W., L.A.C., A.D.), and Department of Molecular and Cellular Biochemistry (C.W.V.K.), University of Kentucky, Lexington; and The Cardiovascular Key Lab of Zhejiang Province, Department of Cardiology, the Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China (Y.X., J.-a.W.).From the Saha Cardiovascular Research Center (C.W., Y.X., H.L., D.A.H., A.B., J.J.M., A.D.), Department of Pharmacology and Nutritional Sciences (C.W., L.A.C., A.D.), and Department of Molecular and Cellular Biochemistry (C.W.V.K.), University of Kentucky, Lexington; and The Cardiovascular Key Lab of Zhejiang Province, Department of Cardiology, the Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China (Y.X., J.-a.W.).From the Saha Cardiovascular Research Center (C.W., Y.X., H.L., D.A.H., A.B., J.J.M., A.D.), Department of Pharmacology and Nutritional Sciences (C.W., L.A.C., A.D.), and Department of Molecular and Cellular Biochemistry (C.W.V.K.), University of Kentucky, Lexington; and The Cardiovascular Key Lab of Zhejiang Province, Department of Cardiology, the Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China (Y.X., J.-a.W.).From the Saha Cardiovascular Research Center (C.W., Y.X., H.L., D.A.H., A.B., J.J.M., A.D.), Department of Pharmacology and Nutritional Sciences (C.W., L.A.C., A.D.), and Department of Molecular and Cellular Biochemistry (C.W.V.K.), University of Kentucky, Lexington; and The Cardiovascular Key Lab of Zhejiang Province, Department of Cardiology, the Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China (Y.X., J.-a.W.).From the Saha Cardiovascular Research Center (C.W., Y.X., H.L., D.A.H., A.B., J.J.M., A.D.), Department of Pharmacology and Nutritional Sciences (C.W., L.A.C., A.D.), and Department of Molecular and Cellular Biochemistry (C.W.V.K.), University of Kentucky, Lexington; and The Cardiovascular Key Lab of Zhejiang Province, Department of Cardiology, the Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China (Y.X., J.-a.W.).From the Saha Cardiovascular Research Center (C.W., Y.X., H.L., D.A.H., A.B., J.J.M., A.D.), Department of Pharmacology and Nutritional Sciences (C.W., L.A.C., A.D.), and Department of Molecular and Cellular Biochemistry (C.W.V.K.), University of Kentucky, Lexington; and The Cardiovascular Key Lab of Zhejiang Province, Department of Cardiology, the Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China (Y.X., J.-a.W.).From the Saha Cardiovascular Research Center (C.W., Y.X., H.L., D.A.H., A.B., J.J.M., A.D.), Department of Pharmacology and Nutritional Sciences (C.W., L.A.C., A.D.), and Department of Molecular and Cellular Biochemistry (C.W.V.K.), University of Kentucky, Lexington; and The Cardiovascular Key Lab of Zhejiang Province, Department of Cardiology, the Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China (Y.X., J.-a.W.).From the Saha Cardiovascular Research Center (C.W., Y.X., H.L., D.A.H., A.B., J.J.M., A.D.), Department of Pharmacology and Nutritional Sciences (C.W., L.A.C., A.D.), and Department of Molecular and Cellular Biochemistry (C.W.V.K.), University of Kentucky, Lexington; and The Cardiovascular Key Lab of Zhejiang Province, Department of Cardiology, the Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China (Y.X., J.-a.W.). Alan.Daugherty@uky.edu wja@zju.edu.cn.From the Saha Cardiovascular Research Center (C.W., Y.X., H.L., D.A.H., A.B., J.J.M., A.D.), Department of Pharmacology and Nutritional Sciences (C.W., L.A.C., A.D.), and Department of Molecular and Cellular Biochemistry (C.W.V.K.), University of Kentucky, Lexington; and The Cardiovascular Key Lab of Zhejiang Province, Department of Cardiology, the Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China (Y.X., J.-a.W.). Alan.Daugherty@uky.edu wja@zju.edu.cn.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25691624

Citation

Wu, Congqing, et al. "Cys18-Cys137 Disulfide Bond in Mouse Angiotensinogen Does Not Affect AngII-dependent Functions in Vivo." Hypertension (Dallas, Tex. : 1979), vol. 65, no. 4, 2015, pp. 800-5.
Wu C, Xu Y, Lu H, et al. Cys18-Cys137 disulfide bond in mouse angiotensinogen does not affect AngII-dependent functions in vivo. Hypertension. 2015;65(4):800-5.
Wu, C., Xu, Y., Lu, H., Howatt, D. A., Balakrishnan, A., Moorleghen, J. J., ... Daugherty, A. (2015). Cys18-Cys137 disulfide bond in mouse angiotensinogen does not affect AngII-dependent functions in vivo. Hypertension (Dallas, Tex. : 1979), 65(4), pp. 800-5. doi:10.1161/HYPERTENSIONAHA.115.05166.
Wu C, et al. Cys18-Cys137 Disulfide Bond in Mouse Angiotensinogen Does Not Affect AngII-dependent Functions in Vivo. Hypertension. 2015;65(4):800-5. PubMed PMID: 25691624.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cys18-Cys137 disulfide bond in mouse angiotensinogen does not affect AngII-dependent functions in vivo. AU - Wu,Congqing, AU - Xu,Yinchuan, AU - Lu,Hong, AU - Howatt,Deborah A, AU - Balakrishnan,Anju, AU - Moorleghen,Jessica J, AU - Vander Kooi,Craig W, AU - Cassis,Lisa A, AU - Wang,Jian-an, AU - Daugherty,Alan, Y1 - 2015/02/17/ PY - 2015/2/19/entrez PY - 2015/2/19/pubmed PY - 2015/5/13/medline KW - angiotensin KW - angiotensinogen KW - atherosclerosis KW - blood pressure SP - 800 EP - 5 JF - Hypertension (Dallas, Tex. : 1979) JO - Hypertension VL - 65 IS - 4 N2 - Renin cleavage of angiotensinogen (AGT) releases angiotensin I (AngI) in the initial step of producing all angiotensin peptides. It has been suggested recently that redox regulation of a disulfide bond in AGT involving Cys18-Cys137 may be important to its renin cleavage efficiency in vivo. The purpose of this study was to test this prediction in a mouse model by comparing AngII production and AngII-dependent functions in mice expressing wild-type AGT versus a mutated form of AGT lacking the disulfide bond. Wild-type (hepAGT+/+) and hepatocyte-specific AGT-deficient (hepAGT-/-) littermates were developed in an low-density lipoprotein receptor -/- background. hepAGT+/+ mice were injected intraperitoneally with adeno-associated viral (AAV) vector containing a null insert. hepAGT-/- mice were injected with AAV containing a null insert, wild-type AGT or Cys18Ser and Cys137Ser mutated AGT. Two weeks after AAV injection, mice were fed a Western diet for 12 weeks. Administration of AAV containing either form of AGT led to similar plasma AGT concentrations in hepAGT-/- mice. High plasma renin concentrations in hepAGT-/- mice were suppressed equally by both forms of AGT, which were accompanied by comparable increases of plasma AngII concentrations similar to hepAGT+/+ mice. AAV-driven expression of both forms of AGT led to equivalent increases of systolic blood pressure and augmentation of atherosclerotic lesion size in hepAGT-/- mice. These measurements were comparable to systolic blood pressure and atherosclerotic lesions in hepAGT+/+ mice. These data indicate that the Cys18-Cys137 disulfide bond in AGT is dispensable for AngII production and AngII-dependent functions in mice. SN - 1524-4563 UR - https://www.unboundmedicine.com/medline/citation/25691624/Cys18_Cys137_disulfide_bond_in_mouse_angiotensinogen_does_not_affect_AngII_dependent_functions_in_vivo_ L2 - http://www.ahajournals.org/doi/full/10.1161/HYPERTENSIONAHA.115.05166?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -