当前位置： SCI文献检索 > Cardiovascular Toxicology期刊下所有文献 > Role of Peroxynitrite-Induced Activation of Poly(ADP-Ribose) Polymerase (PARP) in Circulatory Shock and Related Pathological Conditions.

Role of Peroxynitrite-Induced Activation of Poly(ADP-Ribose) Polymerase (PARP) in Circulatory Shock and Related Pathological Conditions.

Abstract：

:Peroxynitrite is a powerful oxidant, formed from the reaction of nitric oxide and superoxide. It is known to interact and modify different biological molecules such as DNA, lipids and proteins leading to alterations in their structure and functions. These events elicit various cellular responses, including cell signaling, causing oxidative damage and committing cells to apoptosis or necrosis. This review discusses nitrosative stress-induced modification in the DNA molecule that results in the formation of 8-nitroguanine and 8-oxoguanine, and its role in disease conditions. Different approaches of cell death, such as necrosis and apoptosis, are modulated by cellular high-energy species, such as ATP and NAD+. High concentrations of peroxynitrite are known to cause necrosis, whereas low concentrations lead to apoptosis. Any damage to DNA activates cellular DNA repair machinery, like poly(ADP-ribose) polymerase (PARP). PARP-1, an isoform of PARP, is a DNA nick-sensing enzyme that becomes activated upon sensing DNA breakage and triggers the cleavage of NAD+ into nicotinamide and ADP-ribose and polymerizes the latter on nuclear acceptor proteins. Peroxynitrite-induced hyperactivation of PARP causes depletion of NAD+ and ATP culminating cell dysfunction, necrosis or apoptosis. This mechanistic pathway is implicated in the pathogenesis of a variety of diseases, including circulatory shock (which is characterized by cellular hypoxia triggered by systemic altered perfusion and tissue oxygen utilization leading end-organ dysfunction), sepsis and inflammation, injuries of the lung and the intestine. The cytotoxic effects of peroxynitrite centering on the participation of PARP-1 and ADP-ribose in previously stated diseases have also been discussed in this review.

journal_name

Cardiovasc Toxicol

journal_title

Cardiovascular toxicology

authors

Islam BU,Habib S,Ali SA,Moinuddin,Ali A

doi

10.1007/s12012-016-9394-7

subject

Has Abstract

pub_date

2017-10-01 00:00:00

pages

373-383

issue

eissn

1530-7905

issn

1559-0259

pii

10.1007/s12012-016-9394-7

journal_volume

pub_type

杂志文章,评审

在线工具

Role of Peroxynitrite-Induced Activation of Poly(ADP-Ribose) Polymerase (PARP) in Circulatory Shock and Related Pathological Conditions.