Inhibition of poly (ADP-ribose) Synthetase Attenuates Neutrophil Recruitment and Exerts Antiinflammatory Effects

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Inhibition of poly (ADP-ribose) Synthetase Attenuates Neutrophil Recruitment and Exerts Antiinflammatory Effects

A cytotoxic cycle triggered by DNA single-strand breakage and poly (ADP-ribose) synthetase activation has been shown to contribute to the cellular injury during various forms of oxidant stress in vitro. The aim of this study was to investigate the role of poly (ADP-ribose) synthetase (PARS) in the process of neutrophil recruitment and in development of local and systemic inflammation. In pharma...

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Role of poly(ADP-ribose) synthetase in pulmonary leukocyte recruitment.

During systemic inflammation, recruitment and activation of leukocytes in the pulmonary microcirculation may result in a potentially life-threatening acute lung injury. We elucidated the role of the poly(ADP-ribose) synthetase (PARS), a nucleotide-polymerizing enzyme, in the regulation of leukocyte recruitment within the lung with regard to the localization in the pulmonary microcirculation and...

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Novel inhibitors of poly(ADP-ribose) synthetase.

In a search for new inhibitors of the nuclear enzyme poly(ADP-ribose) synthetase, it was found that various benzamides substituted in the 3-position were the most inhibitory compounds found to date. Two of the benzamides, 3-aminobenzamide and 3-methoxybenzamide, were found to be competitive inhibitors, with Ki values or less than 2 microM.

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Cardioprotective effects of poly(ADP-ribose) polymerase inhibition.

Free radical and oxidant production in cardiac myocytes during ischemia/reperfusion, cardiomyopathy, cardiotoxic drug exposure and ageing leads to DNA strand-breakage which activates the nuclear enzyme poly(ADP-ribose) polymerase (PARP) and initiates an energy consuming, inefficient cellular metabolic cycle with transfer of the ADP-ribosyl moiety of NAD+ to protein acceptors. These processes le...

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Inhibition of Poly ( ADP - ribose ) polymerase – PARP

Inhibition of the DNA repair enzyme PARP-1 has been extensively investigated in the pre-clinical setting as a strategy for chemoor radio-potentiation. Recent evidence has suggested that PARP inhibitors may be active as single agents in certain rare inherited cancers which carry DNA repair defects. Potent PARP-1 inhibitors have entered early clinical trials in cancer patients in the last 3 years...

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ژورنال

عنوان ژورنال: Journal of Experimental Medicine

سال: 1997

ISSN: 0022-1007,1540-9538

DOI: 10.1084/jem.186.7.1041