Inhibition of poly(ADP-ribose) polymerase activity protects hippocampal cells against morphological and ultrastructural alteration evoked by ischemia-reperfusion injury.
Poly(ADP-ribose) polymerase 1 (PARP-1 EC 2.4.2.30) is a nuclear enzyme that plays an important role in cell survival and death. PARP is involved in DNA repair machinery, however, massive DNA damage leads to over-activation of PARP-1 and to depletion of its substrate bNAD+ which causes cell death. Our previous study indicated that the PARP activity was significantly activated during ischemia-reperfusion injury. In this study we investigated the effect of PARP inhibitor, 3-aminobenzamide (3-AB) on intracellular organelles alteration. Gerbils were submitted to 3 and 10 min transient global ischemia followed by recirculation and survival for 1 till 7 days. The histological and electron microscopic examination indicated a pronounced protective effect of 3-AB on the swelling of astrocytes and neurons 1 day after 3 and 10 min ischemic insult. It decreased also the swelling of pericytes. 3-AB decreases evoked by ischemia swelling of mitochondria and Golgi apparatus. The significant ameliorating effect of 3-AB was also observed on the 7th day of reperfusion after 3 min ischemia and was also visible on the 1st day after 10 min ischemia. However, 7 days after prolonged 10 min ischemia almost all neurons in the CA1 hippocampal layer died and 3-AB was not able to protect these cells. In spite of that, 3-AB markedly decreased immunostaining of glial fibrillary acidic protein (GFAP), which was enhanced in the stratum: oriens, radiatum and lacunosum-moleculare at the 7th day after 10 min ischemia. These data indicated that inhibition of PARP may have a protective effect on neuronal cells affected by ischemia-reperfusion injury.
Strosznajder
Robert
R
Department of Respiratory Research, Warsaw, Poland. roberts@cmdik.pan.pl
Gadamski
Roman
R
Walski
Michał
M
D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000473:pathology* / Q000648:ultrastructure; D001549:Benzamides / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005849:Gerbillinae; D005904:Glial Fibrillary Acidic Protein; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D020925:Hypoxia-Ischemia, Brain / Q000201:enzymology / Q000473:pathology; D008297:Male; D046529:Microscopy, Electron, Transmission; D009474:Neurons / Q000187:drug effects / Q000473:pathology* / Q000648:ultrastructure; D018696:Neuroprotective Agents / Q000494:pharmacology; D020286:Pericytes / Q000187:drug effects / Q000473:pathology* / Q000648:ultrastructure; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*; D015427:Reperfusion Injury / Q000201:enzymology / Q000473:pathology*; D013997:Time Factors
D001549:Benzamides; D004791:Enzyme Inhibitors; D005904:Glial Fibrillary Acidic Protein; D018696:Neuroprotective Agents; C025160:3-aminobenzamide; D011065:Poly(ADP-ribose) Polymerases