Poly(ADP-ribose) polymerase-1 inhibition protects the brain against systemic inflammation |
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| Institution: | 1. Department of Cellular Signalling, Medical Research Centre, Polish Academy of Sciences, 5 Pawińskiego St., PL-02106 Warsaw, Poland;2. Department of the Cell Ultrastructure, Medical Research Centre, Polish Academy of Sciences, 5 Pawińskiego St., PL-02106 Warsaw, Poland;1. Department of Biochemistry and Molecular Biology, Yeungnam University College of Medicine, 317-1, Daemyung-dong, Daegu, Republic of Korea;2. Department of Pharmacology and Smart-Aging Convergence Research Center, Yeungnam University College of Medicine, 317-1, Daemyung-dong, Daegu, Republic of Korea;3. Department of Anatomy, Kyungpook National University School of Medicine, 700-422, Daegu, Republic of Korea;1. Harvard Medical School and Division of Gastroenterology, Boston Children’s Hospital, Boston, MA, USA;1. University of Guam, School of Nursing and Health Sciences, Room 103, Mangilao, GU 96923, United States;2. University of Hawai`i at Mānoa, Office of Public Health Studies, Biomed D-201, Honolulu, HI 96822, United States;3. Commonwealth Health Care Corporation, Division of Public Health, Non-Communicable Disease Bureau, P.O. Box 500409, Saipan, MP 96950, United States;4. University of Guam, Tropical Agriculture Undergraduate Program, Mangilao, GU 96923, United States;5. University of Hawai`i at Mānoa, College of Tropical Agriculture and Human Resources, Honolulu, HI 96822, United States;6. University of Hawai`i Cancer Center, 701 Ilalo St., Honolulu, HI 96817, United States;7. University of Guam, School of Education, 208 K, Mangilao, GU 96923, United States;1. Department of Paediatrics, All India Institute of Medical Sciences, Patna, Bihar, India;2. Department of Radiodiagnosis, All India Institute of Medical Sciences, Patna, Bihar, India |
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| Abstract: | Poly(ADP-ribose) polymerase-1 (PARP-1) is involved in DNA repair, but its overactivation can induce cell death. Our aim was to investigate the role of PARP-1 in activation of programmed cell death processes in the brain during systemic inflammation.Our data indicated that lipopolysaccharide (1 mg/kg b.w., i.p.)-evoked systemic inflammation enhanced PARP-1 activity in the mouse brain, leading to the lowering of β-NAD+ concentration, to translocation of apoptosis inducing factor from mitochondria to the nucleus, and to enhanced lipid peroxidation. Inhibitor of PARP-1, 3-aminobenzamide (30 mg/kg b.w., i.p.), protected the brain against prooxidative and cell death processes, suggesting involvement of PARP-1 in systemic inflammation-related processes in the brain. |
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