Poly (ADP-Ribose) Polymerase 1 Mediated Arginase II Activation Is Responsible for Oxidized LDL-Induced Endothelial Dysfunction

Frontiers in Pharmacology
Qi WangMing-Xiang Zhang

Abstract

It is well known that arginase II leads to decreased synthesis of nitric oxide (NO) by competing with endothelial nitric oxide synthase (eNOS) for their same substrate L-arginine. However, the regulatory mechanisms of arginase II production remain unclear. In this study, we hypothesized that poly- (ADP-ribose) transferase/polymerase-1 (PARP-1) may be a critical factor responsible for ox-LDL (oxidized Low Density Lipoprotein)-enhanced arginase II activity. We used serial deletions within plasmid constructs and found that a core promoter region of arginase II was located at the element of -774 to -738 bp and PARP-1 was identified specifically binding to this region. Inhibition of PARP-1 markedly reduced the endogenous arginase II expression and enhanced eNOS and NO production. Similarly, ox-LDL-induced increase in arginase II production and eNOS and NO reduction was substantially abolished by PARP-1 inhibition both in vitro and in vivo. Significant decrease in arginase II expression and increase in eNOS expression and NO levels, as well as improved endothelial function were observed in PARP-1-/- mice. The underlying mechanisms of ox-LDL-induced changes of PARP-1 expression involved migration of phosphorylated ERK2 into nuclei and...Continue Reading

References

Nov 25, 2000·Journal of Applied Physiology·B WintersD E Berkowitz
Jun 24, 2004·The Journal of Pharmacology and Experimental Therapeutics·Pál PacherCsaba Szabó
Mar 22, 2006·The Journal of Cell Biology·Piergiorgio Percipalle, Neus Visa
Jul 6, 2006·Nucleic Acids Research·Marc van DijkAlexandre M J J Bonvin
Mar 1, 2008·Circulation Research·Sungwoo RyooDan E Berkowitz
Apr 9, 2008·The Journal of Biological Chemistry·Ming-Xiang ZhangXing Li Wang
Jul 11, 2008·Molecular Biology of the Cell·Ming-Xiang ZhangXing Li Wang
Feb 12, 2009·Proceedings of the National Academy of Sciences of the United States of America·Qun-Ye ZhangZhu Chen
Mar 13, 2009·CA: a Cancer Journal for Clinicians·Wen W Ma, Alex A Adjei
May 19, 2010·Cardiovascular Research·Qiang ShenSarah Y Yuan

❮ Previous
Next ❯

Citations

May 17, 2019·DNA and Cell Biology·Wenxi PengDangheng Wei
Feb 5, 2021·Mechanisms of Ageing and Development·Jacopo SabbatinelliFabiola Olivieri
Apr 4, 2021·Biomedicines·Juan M Suárez-RiveroJosé A Sánchez-Alcázar
Aug 28, 2021·Progress in Lipid Research·Magdolna SzántóPeter Bai

❮ Previous
Next ❯

Methods Mentioned

BETA
PCR
Transfection
NMR
immunoprecipitation
flow cytometry
confocal microscopy
ChIP
nuclear translocation
co-immunoprecipitation
acetylation

Software Mentioned

Beacon Designer
SPSS
3D
Cell Quest Pro
HADDOCK
DART

Related Concepts

Related Feeds

Cell Migration

Cell migration is involved in a variety of physiological and pathological processes such as embryonic development, cancer metastasis, blood vessel formation and remoulding, tissue regeneration, immune surveillance and inflammation. Here is the latest research.