NDLI: Argininosuccinate Synthetase Is a Functional Target for a Snake Venom Anti-hypertensive Peptide

Content Provider	PubMed Central
Author	Guerreiro, Juliano R. Lameu, Claudiana Oliveira, Eduardo F. Klitzke, Clécio F. Melo, Robson L. Linares, Edlaine Augusto, Ohara Fox, Jay W. Lebrun, Ivo Serrano, Solange M. T. Camargo, Antonio C. M.
Abstract	Bj-BPP-10c is a bioactive proline-rich decapeptide, part of the C-type natriuretic peptide precursor, expressed in the brain and in the venom gland of Bothrops jararaca. We recently showed that Bj-BPP-10c displays a strong, sustained anti-hypertensive effect in spontaneous hypertensive rats (SHR), without causing any effect in normotensive rats, by a pharmacological effect independent of angiotensin-converting enzyme inhibition. Therefore, we hypothesized that another mechanism should be involved in the peptide activity. Here we used affinity chromatography to search for kidney cytosolic proteins with affinity for Bj-BPP-10c and demonstrate that argininosuccinate synthetase (AsS) is the major protein binding to the peptide. More importantly, this interaction activates the catalytic activity of AsS in a dose-de pend ent manner. AsS is recognized as an important player of the citrulline-NO cycle that represents a potential limiting step in NO synthesis. Accordingly, the functional interaction of Bj-BPP-10c and AsS was evidenced by the following effects promoted by the peptide: (i) increase of NO metabolite production in human umbilical vein endothelial cell culture and of arginine in human embryonic kidney cells and (ii) increase of arginine plasma concentration in SHR. Moreover, α-methyl-dl-aspartic acid, a specific AsS inhibitor, significantly reduced the anti-hypertensive activity of Bj-BPP-10c in SHR. Taken together, these results suggest that AsS plays a role in the anti-hypertensive action of Bj-BPP-10c. Therefore, we propose the activation of AsS as a new mechanism for the anti-hypertensive effect of Bj-BPP-10c in SHR and AsS as a novel target for the therapy of hypertension-related diseases.
Related Links	http://dx.doi.org/10.1074/jbc.m109.021089
Ending Page	20033
Page Count	12
Starting Page	20022
File Format	PDF
ISSN	00219258
e-ISSN	1083351X
Journal	The Journal of Biological Chemistry
Issue Number	30
Volume Number	284
Language	English
Publisher	American Society for Biochemistry and Molecular Biology
Publisher Date	2009-07-24
Access Restriction	Open
Rights Holder	American Society for Biochemistry and Molecular Biology
Subject Keyword	Cell Biology Biochemistry Molecular Biology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Cell Biology Biochemistry Molecular Biology

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

Argininosuccinate Synthetase Is a Functional Target for a Snake Venom Anti-hypertensive Peptide ROLE IN ARGININE AND NITRIC OXIDE PRODUCTION

Argininosuccinate synthetase is a functional target for a snake venom anti-hypertensive peptide: role in arginine and nitric oxide production.

A potent antiplatelet peptide, triflavin, from Trimeresurus flavoviridis snake venom.

Annexin A2 Is a Molecular Target for TM601, a Peptide with Tumor-targeting and Anti-angiogenic Effects

Lysyl-tRNA Synthetase Is a Target for Mutant SOD1 Toxicity in Mitochondria*

Anti-cobra venom activity of plant Andrographis paniculata and its comparison with polyvalent anti-snake venom

inhibition of dehydrogenases by snake venom

Crystal Structure of Argininosuccinate Synthetase fromThermus thermophilus HB8 STRUCTURAL BASIS FOR THE CATALYTIC ACTION

Phospholipase B in snake venoms and bee venom

Argininosuccinate Synthetase Is a Functional Target for a Snake Venom Anti-hypertensive Peptide

Similar Documents

Argininosuccinate Synthetase Is a Functional Target for a Snake Venom Anti-hypertensive Peptide ROLE IN ARGININE AND NITRIC OXIDE PRODUCTION

Argininosuccinate synthetase is a functional target for a snake venom anti-hypertensive peptide: role in arginine and nitric oxide production.

A potent antiplatelet peptide, triflavin, from Trimeresurus flavoviridis snake venom.

Annexin A2 Is a Molecular Target for TM601, a Peptide with Tumor-targeting and Anti-angiogenic Effects

Lysyl-tRNA Synthetase Is a Target for Mutant SOD1 Toxicity in Mitochondria*

Anti-cobra venom activity of plant Andrographis paniculata and its comparison with polyvalent anti-snake venom

inhibition of dehydrogenases by snake venom

Crystal Structure of Argininosuccinate Synthetase fromThermus thermophilus HB8 STRUCTURAL BASIS FOR THE CATALYTIC ACTION

Phospholipase B in snake venoms and bee venom

Argininosuccinate Synthetase Is a Functional Target for a Snake Venom Anti-hypertensive Peptide