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

Comments

Editorial

01 May 2022 : Editorial  

Editorial: Cardiovascular Complications at One Year After SARS-CoV-2 Infection are Independent of Underlying Cardiovascular Risk Factors or Severity of COVID-19

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

DOI: 10.12659/MSM.937048

Med Sci Monit 2022; 28:e937048

SARS-CoV-2/COVID-19

24 May 2022 : Clinical Research  

Screening for SARS-CoV-2 Infection in Students at the Medical University of Warsaw, Poland Between November...

Med Sci Monit In Press; DOI: 10.12659/MSM.936962  

04 May 2022 : Clinical Research  

Effects of Wearing Face Masks on Exercise Capacity and Ventilatory Anaerobic Threshold in Healthy Subjects ...

Med Sci Monit In Press; DOI: 10.12659/MSM.936069  

27 May 2022 : Clinical Research  

Factors Associated with Falls During Hospitalization for Coronavirus Disease 2019 (COVID-19)

Med Sci Monit 2022; 28:e936547

In Press

27 May 2022 : Clinical Research  

Prognostic Significance of Preoperative Integrated Liver Inflammatory Score in Patients with Hepatocellular...

Med Sci Monit In Press; DOI: 10.12659/MSM.937005  

25 May 2022 : Review article  

Narrative Review of the Mechanism of Hip Prosthesis Dislocation and Methods to Reduce the Risk of Dislocation

Med Sci Monit In Press; DOI: 10.12659/MSM.935665  

24 May 2022 : Clinical Research  

Remimazolam Tosilate Sedation with Adjuvant Sufentanil in Chinese Patients with Liver Cirrhosis Undergoing ...

Med Sci Monit In Press; DOI: 10.12659/MSM.936580  

24 May 2022 : Clinical Research  

Screening for SARS-CoV-2 Infection in Students at the Medical University of Warsaw, Poland Between November...

Med Sci Monit In Press; DOI: 10.12659/MSM.936962  

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

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

01 Jan 2022 : Editorial  

Editorial: Current Status of Oral Antiviral Drug Treatments for SARS-CoV-2 Infection in Non-Hospitalized Pa...

DOI :10.12659/MSM.935952

Med Sci Monit 2022; 28:e935952

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