Protective effects of the PARP-1 inhibitor PJ34 in hypoxic-reoxygenated cardiomyoblasts

Fiorillo, Claudia; Ponziani, Vanessa; Giannini, L.; Cecchi, Cristina; Celli, Alessandra; Nassi, Niccolò; Lanzilao, Luisa; Caporale, Roberto; Nassi, Paolo

doi:10.1007/s00018-006-6345-7

Cited by 42 publications

(35 citation statements)

References 36 publications

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“…Along with the recognition of the wide pathophysiological relevance of regulated necrosis, the role of apoptosis in the pathogenesis of myocardial infarction and heart failure is being reconsidered. 126 Murine models of ischemia/reperfusion demonstrate that the pharmacological or genetic inhibition of proteins involved in regulated necrosis, including cyclophilin, 101,102 RIPK1, 127 and PARP, 128 provides consistent cardioprotective effects. Such a conceptual shift has been paralleled by the discovery of human cardiac stem cells, 129,130 de facto revolutionizing the conception of the heart as a merely postmitotic organ and paving new ways for the development of cardioregenerative strategies.…”

Section: Mitochondrial Regulation Of Cell Deathmentioning

confidence: 99%

Mitochondrial Control of Cellular Life, Stress, and Death

Galluzzi

Kepp²,

Trojel-Hansen³

et al. 2012

Circulation Research

452

318

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Since the discovery that mitochondrial membrane permeabilization represents a critical step in the regulation of intrinsic apoptosis, mitochondria have been viewed as pluripotent organelles, controlling cell death as well as several aspects of cell survival. Mitochondria constitute the most prominent source of ATP and are implicated in multiple anabolic and catabolic circuitries. In addition, mitochondria coordinate cell-wide stress responses, such as autophagy, and control nonapoptotic cell death routines, such as regulated necrosis. Thus, mitochondria seem to regulate a continuum of cellular functions, spanning from physiological metabolism to stress responses and death. The involvement of mitochondria in both vital and lethal processes is crucial for both embryonic and postembryonic development, as well as for the maintenance of adult tissue homeostasis. In line with this notion, primary mitochondrial defects or alterations in the signaling pathways that converge on or emanate from mitochondria underpin a large number of human diseases, including premature aging, neurodegenerative disorders, cardiovascular disorders, and cancer. Here, we provide an overview of the molecular mechanisms that enable mitochondria to sustain cell survival, coordinate stress responses, and mediate cell death, linking these pathways—whenever relevant—to cardiovascular health and disease.

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Section: Mitochondrial Regulation Of Cell Deathmentioning

confidence: 99%

Mitochondrial Control of Cellular Life, Stress, and Death

Galluzzi

Kepp²,

Trojel-Hansen³

et al. 2012

Circulation Research

452

318

View full text Add to dashboard Cite

show abstract

“…Further, excessive activation of PARP has also been reported to enhance expression of proinflammatory cytokines and chemokines (Virag and Szabo 2002;Young et al, 2005;Schreiber et al, 2006). PJ34, a selective PARP-1 inhibitor, has been documented to reduce hypoxic-reoxygenation induced necrosis and apoptosis in cardiomyoblasts (H9c2) (Fiorillo et al, 2006). Aging-associated chronic cardiovascular dysfunction has been improved with a PARP-inhibitor (Radovits et al, 2007).…”

Section: Introductionmentioning

confidence: 96%

Protective effects of caspase-9 and poly(ADP-ribose) polymerase inhibitors on ischemia-reperfusion-induced myocardial injury

Sodhi¹,

Singh

et al. 2009

Arch. Pharm. Res.

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The present study was designed to investigate the cardio-protective effect of Ac-LEDH-cmk a selective caspase-9 inhibitor and 5-aminoisoquinolinone a selective Poly (ADP-ribose) polymerase inhibitor on ischemia and reperfusion induced apoptotic and necrotic cell death in rats. Isolated rat hearts were exposed to 30 minutes of global ischemia followed by 120 minutes of reperfusion using Langendorff's apparatus. Myocardial injury was assessed in the terms of infarct size, release of lactate dehydrogenase, creatine kinase enzymes and apoptotic index was assessed by DNA smearing on agarose gel electrophoresis. Pretreatments with specific inhibitor of caspase-9, Ac-LEHD-cmk (0.07 muM and 0.105 muM), and inhibitor of PARP, 5-aminoisoquinolinone (5 microM and 7.5 muM), significantly attenuated I/R induced increase in infarct size, release of lactate dehydrogenase and creatine kinase in the coronary effluent, and apoptotic index. Therefore, it may be concluded that inhibition of caspase-9 and PARP prevent ischemia and reperfusion-induced activation of apoptotic cascade and necrosis in rat myocardium.

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“…DNA damage-triggered signaling and execution of apoptosis depend on the p53 status, death-receptor responsiveness, and most importantly, DNA repair capacity [21]. p53 could repair the impaired DNA to protect cells from DNA damage, and also facilitate cell apoptosis once the DNA damage could not be soundly repaired [22].…”

Section: Discussionmentioning

confidence: 99%

3-Nitro-naphthalimide and nitrogen mustard conjugate NNM-25 induces hepatocellular carcinoma apoptosis via PARP-1/p53 pathway

Xie

Zhang

et al. 2012

Apoptosis

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Hepatocellular carcinoma (HCC) is one of the main causes of death in cancer. Some naphthalimide derivatives exert high anti-proliferative effects on HCC. In this study, it is confirmed that 3-nitro-naphthalimide and nitrogen mustard conjugate (NNM-25), a novel compound conjugated by NNM-25, displayed more potent therapeutic action on HCC, both in vivo and in vitro, than amonafide, a naphthalimide drug in clinical trials. More importantly, preliminary toxicological evaluation also supported that NNM-25 exhibited less systemic toxicity than amonafide at the therapeutic dose. The antitumor mechanism of conjugates of naphthalimides with nitrogen mustard remains poorly understood up to now. Here, we first reported that apoptosis might be the terminal fate of cancer cells treated with NNM-25. Inhibition of p53 by siRNA resulted in a significant decrease of NNM-25-induced apoptosis, which corroborated that p53 played a vital role in the cell apoptosis triggered by NNM-25. NNM-25 inhibited the PARP-1 activity, AKT phosphorylation, up-regulated the protein expression of p53, Bad, and mTOR as well as down-regulating the protein expression of Bcl-2 and decreasing mitochondrial membrane potential. It also facilitated cytochrome c release from mitochondria to cytoplasm, activated caspase 8, caspase 9, and caspase 3 in HepG2 cells in vitro, as also authenticated in H22 tumor-bearing mice in vivo. Collectively, the conjugation of naphthalimides with nitrogen mustard provides favorable biological activity and thus is a valuable strategy for future drug design in HCC therapy.

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Protective effects of the PARP-1 inhibitor PJ34 in hypoxic-reoxygenated cardiomyoblasts

Cited by 42 publications

References 36 publications

Mitochondrial Control of Cellular Life, Stress, and Death

Mitochondrial Control of Cellular Life, Stress, and Death

Protective effects of caspase-9 and poly(ADP-ribose) polymerase inhibitors on ischemia-reperfusion-induced myocardial injury

3-Nitro-naphthalimide and nitrogen mustard conjugate NNM-25 induces hepatocellular carcinoma apoptosis via PARP-1/p53 pathway

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