Logo Medical Science Monitor

Call: +1.631.470.9640
Mon - Fri 10:00 am - 02:00 pm EST

Contact Us

Logo Medical Science Monitor Logo Medical Science Monitor Logo Medical Science Monitor

02 May 2003

Role of poly(ADP-ribose) polymerase (PARP) activation in the mitochondrial to nuclear translocation of apoptosis inducing factor (AIF) in stroke

K. Komjati, C. Szabo

Med Sci Monit 2003; 9(1): 32- :: ID: 15091

Abstract

Focal cerebral ischemia activates the nuclear protein poly(ADP-ribose) polymerase (PARP) by single DNA strand breaks which leads to energy depletion and cell death and significantly contributes to the pathogenesis of stroke. Apoptosis Inducing Factor (AIF) is a flavoprotein that is normally confined to the mithochondrial intermembrane space, yet translocates to the nucleus, as shown in several in vitro models of neuronal injury. Here we examined the AIF tranclocation changes in a rat model of focal cerebral ischemia and using INO-1001, a novel potent inhibitor of PARP, we determined the role of PARP activation in the process of AIF translocation in vivo. We used a standard rat middle cerebral artery occlusion model with 2h ischemia and 22h reperfusion. INO-1001 (3 mg/kg/24h) provided a 85% reduction in total hemispheric infarct size, when its administration began 2 hours after the MCA occlusion. INO-1001 attenuated the accumulation of poly(ADP-ribose) in the ischemic/reperfused hemisphere and reduced the accumulation of APP in the white matter of the affected hemisphere, consistently with protection against neuronal necrosis and axonal damage, respectively. Immunocytochemical analysis showed the appearance of AIF labeling in neuronal nuclei of the border zone ischemic area in the striatum after stroke. Cytoplasmatic (axonal) AIF staining was significantly diminished in the necrotic core of the striatum, while it was somewhat enhanced at the borderline ischemic territories of the white matter (ie. in the inner layer of the external capsule). Inhibition of PARP with INO-1001 reshifted the location of the apoptotic marker to the axons in the ipsilateral striatum. Thus, PARP inhibition provides marked protection in the rat model of MCA occlusion induced stroke, both in terms of histological damage (perykarial and axonal) and in terms of functional parameters. Moreover, PARP appears to be involved in the ischemic nuclear translocation of AIF. References: 1.Yu SW, Wang H, Poitras MF, Coombs C et al: Mediation of PARP-1-dependent cell death by apoptosis-inducing factor. Science, 2002; 297: 259-63 2.Virág L, Szabó C: The therapeutic potential of PARP inhibition. Pharmacological Reviews, 2002; 54: 375-429

Keywords: Ligation, gingivitis, periodontitis, oral flora, Bacteria, peroxynitrite, Nitric Oxide

0 Comments

Editorial

01 August 2022 : Editorial  

Editorial: Long-Term Effects of Symptomatic and Asymptomatic SARS-CoV-2 Infection in Children and the Changing Pathogenesis of Common Childhood Viruses Driven by the COVID-19 Pandemic

Dinah V. Parums
Science Editor, Medical Science Monitor, International Scientific Information, Inc., Melville, NY, USA

DOI: 10.12659/MSM.937927

Med Sci Monit 2022; 28:e937927

In Press

08 Aug 2022 : Clinical Research  

A 3-Year Clinical Evaluation of Endodontically Treated Posterior Teeth Restored with Resin Nanoceramic Comp...

Med Sci Monit In Press; DOI: 10.12659/MSM.937331  

08 Aug 2022 : Clinical Research  

Hemoglobin/Red Blood Cell Distribution Width Ratio in Peripheral Blood Is Positively Associated with Progno...

Med Sci Monit In Press; DOI: 10.12659/MSM.937146  

05 Aug 2022 : Clinical Research  

A Retrospective Study of 98 Elderly Patients with High-Risk Lateral Femoral Wall Intertrochanteric Hip Frac...

Med Sci Monit In Press; DOI: 10.12659/MSM.936923  

04 Aug 2022 : Clinical Research  

Radiological Assessment of Prevalance and Quality of Periapical Status of Endodontic Treatments

Med Sci Monit In Press; DOI: 10.12659/MSM.936569  

Most Viewed Current Articles

30 Dec 2021 : Clinical Research  

Retrospective Study of Outcomes and Hospitalization Rates of Patients in Italy with a Confirmed Diagnosis o...

DOI :10.12659/MSM.935379

Med Sci Monit 2021; 27:e935379

13 Nov 2021 : Clinical Research  

Acceptance of COVID-19 Vaccination and Its Associated Factors Among Cancer Patients Attending the Oncology ...

DOI :10.12659/MSM.932788

Med Sci Monit 2021; 27:e932788

08 Mar 2022 : Review article  

A Review of the Potential Roles of Antioxidant and Anti-Inflammatory Pharmacological Approaches for the Man...

DOI :10.12659/MSM.936292

Med Sci Monit 2022; 28:e936292

01 Nov 2020 : Review article  

Long-Term Respiratory and Neurological Sequelae of COVID-19

DOI :10.12659/MSM.928996

Med Sci Monit 2020; 26:e928996

Your Privacy

We use cookies to ensure the functionality of our website, to personalize content and advertising, to provide social media features, and to analyze our traffic. If you allow us to do so, we also inform our social media, advertising and analysis partners about your use of our website, You can decise for yourself which categories you you want to deny or allow. Please note that based on your settings not all functionalities of the site are available. View our privacy policy.

Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750