Neuroprotective effects of a novel water-soluble poly(ADP-ribose) polymerase-1 inhibitor, MP-124, in in vitro and in vivo models of cerebral ischemia

Egi, Yasuhiro; Matsuura, Shigeru; Maruyama, Tomoyuki; Fujio, Masakazu; Yuki, Satoshi; Taneno, Akira

doi:10.1016/j.brainres.2011.03.031

Cited by 21 publications

(20 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Following acute oxidative stress, such as radiation, neurons are described to have excessive synthesis of PAR by overactive PARP-1, leading to NAD + /ATP depletion and subsequent neuronal cell death. PARP inhibition has therefore been opted as a neuroprotective strategy for cerebral ischemia and several neurodegenerative diseases, such as Parkinson's disease and ALS [55, 56]. …”

Section: Discussionmentioning

confidence: 99%

PARP inhibition sensitizes childhood high grade glioma, medulloblastoma and ependymoma to radiation

et al. 2011

View full text Add to dashboard Cite

Poly ADP-ribose polymerase (PARP) is a protein involved in single strand break repair. Recently, PARP inhibitors have shown considerable promise in the treatment of several cancers, both in monotherapy and in combination with cytotoxic agents. Synthetic lethal action of PARP inhibitors has been observed in tumors with mutations in double strand break repair pathways. In addition, PARP inhibition potentially enhances sensitivity of tumor cells to DNA damaging agents, including radiotherapy. Aim of this study is to determine the radiosensitizing properties of the PARP inhibitor Olaparib in childhood medulloblastoma, ependymoma and high grade glioma (HGG). Increased PARP1 expression was observed in medulloblastoma, ependymoma and HGG, as compared to non-neoplastic brain tissue. Pediatric high grade glioma, medulloblastoma and ependymoma gene expression profiling revealed that high PARP1 expression is associated with poor prognosis. Cell growth inhibition assays with Olaparib resulted in differential sensitivity, with IC50 values ranging from 1.4 to 8.4 μM, irrespective of tumor type and PARP1 protein expression. Sensitization to radiation was observed in medulloblastoma, ependymoma and HGG cell lines with subcytotoxic concentrations of Olaparib, which coincided with persistence of double strand breaks. Combining PARP inhibitors with radiotherapy in clinical studies in childhood high grade brain tumors may improve therapeutic outcome.

show abstract

Section: Discussionmentioning

confidence: 99%

PARP inhibition sensitizes childhood high grade glioma, medulloblastoma and ependymoma to radiation

et al. 2011

View full text Add to dashboard Cite

show abstract

“…3-Aminobenzamide, a PARP inhibitor, has been shown to have a beneficial effect on renal glomerular and tubular dysfunction in rats’ kidneys subjected to I/R injury. 3-Aminobenzamide had an ameliorating effect on both oxidative and nitrosative stress of the kidneys, which correlated with histopathological evaluation [32]. PARP inhibition by ISO and GPI-15427 has been shown to counteract diabetes-associated increase in poly(ADP-ribose) immunoreactivities in renal glomeruli and tubuli and poly(ADP-ribosyl)ated protein level, as well as renal damage [38].…”

Section: Discussionmentioning

confidence: 99%

Aminoguanidine, a Selective Nitric Oxide Synthase Inhibitor, Attenuates Cyclophosphamide-Induced Renal Damage by Inhibiting Protein Nitration and Poly(ADP-Ribose) Polymerase Activation

Abraham¹,

Rabi

2011

Chemotherapy

View full text Add to dashboard Cite

Background: Cyclophosphamide (CP) is an antineoplastic agent that is used for the treatment of many neoplastic diseases. Renal damage is one of the dose-limiting side effects of CP. Recent studies show that nitrosative stress plays an important role in CP-induced renal damage. Aim: The purpose of our study was to investigate whether aminoguanidine (AG), a selective inducible nitric oxide synthase inhibitor, protects against CP-induced nitrosative stress and renal damage. Method: Renal damage was induced in rats by administration of a single injection of CP at a dose of 150 mg/kg body weight intraperitoneally. For the AG pretreatment studies, the rats were injected intraperitoneally with AG at a dose of 200 mg/kg body weight 1 h before administration of CP. The control rats received AG or saline alone. All the rats were killed 16 h after the administration of CP or saline. Pretreatment with AG prevented CP-induced nitration of protein tyrosine and poly(ADP-ribose) polymerase (PARP) activation. Result: Pretreatment with AG attenuated CP-induced renal damage. The present study demonstrates that AG is effective in preventing CP-induced renal damage and also that the protective effect is from its ability to inhibit nitric oxide-induced protein nitration and PARP activation. Conclusion: The present study shows that AG can prevent CP-induced renal damage by inhibiting protein tyrosine nitration and PARP activation. Thus, a more efficient and comfortable therapy can be achieved for patients in need of CP treatment. AG appears to be a promising drug for the prevention of nephrotoxicity of CP.

show abstract

“…In a recent study, Egi and coworkers could show a reduction in infarct sizes after MCAO using a PARP-1 inhibitor (Egi et al, 2011).…”

Section: Poly(adp-ribose) Polymerasementioning

confidence: 97%

Visualizing Cell Death in Experimental Focal Cerebral Ischemia: Promises, Problems, and Perspectives

Zille

Farr

Przesdzing

et al. 2011

J Cereb Blood Flow Metab

124

View full text Add to dashboard Cite

One of the hallmarks of stroke pathophysiology is the widespread death of many different types of brain cells. As our understanding of the complex disease that is stroke has grown, it is now generally accepted that various different mechanisms can result in cell damage and eventual death. A plethora of techniques is available to identify various pathological features of cell death in stroke; each has its own drawbacks and pitfalls, and most are unable to distinguish between different types of cell death, which partially explains the widespread misuse of many terms. The purpose of this review is to summarize the standard histopathological and immunohistochemical techniques used to identify various pathological features of stroke. We then discuss how these methods should be properly interpreted on the basis of what they are showing, as well as advantages and disadvantages that require consideration. As there is much interest in the visualization of stroke using noninvasive imaging strategies, we also specifically discuss how these techniques can be interpreted within the context of cell death.

show abstract

Neuroprotective effects of a novel water-soluble poly(ADP-ribose) polymerase-1 inhibitor, MP-124, in in vitro and in vivo models of cerebral ischemia

Cited by 21 publications

References 33 publications

PARP inhibition sensitizes childhood high grade glioma, medulloblastoma and ependymoma to radiation

PARP inhibition sensitizes childhood high grade glioma, medulloblastoma and ependymoma to radiation

Aminoguanidine, a Selective Nitric Oxide Synthase Inhibitor, Attenuates Cyclophosphamide-Induced Renal Damage by Inhibiting Protein Nitration and Poly(ADP-Ribose) Polymerase Activation

Visualizing Cell Death in Experimental Focal Cerebral Ischemia: Promises, Problems, and Perspectives

Contact Info

Product

Resources

About