Effect of 3-aminobenzamide, PARP inhibitor, on matrix metalloproteinase-9 level in plasma and brain of ischemic stroke model.
We investigated the effect of poly(ADP-ribose) polymerase (PARP) inhibitor on the levels of plasma and brain matrix metalloproteinase-9 (MMP-9) and the expression of nuclear factor kappa B (NF-kappaB) during experimental focal cerebral ischemia. The 3-aminobenzamide (3-AB), a PARP inhibitor, and saline were administered to 80 Sprague-Dawley rats [3-AB group; 5 rats for plasma sampling, 35 for brain sampling, and 40 for TTC staining] and to 85 rats (10, 35, and 40, respectively), respectively, 10 min before the occlusion of the left middle cerebral artery (MCAo) for 2 h. Infarct volume was measured by TTC staining, the serial levels of plasma and brain MMP-9 were measured by zymography just before and 2, 4, 8, 24, 48, and 72 h after MCAo, brain NF-kappaB activity was determined by Western blotting, and neutrophil infiltration was evaluated by assessing myeloperoxidase activity. Compared with control group, the levels of plasma and brain MMP-9, brain NF-kappaB, and MPO activities were significantly reduced in 3-AB group at each time point (p<0.05). Plasma MMP-9 increased maximally at 4h and then decreased rapidly, brain MMP-9 increased maximally at 24 h and persisted until 72 h, and NF-kappaB increased maximally at 24h and then decreased slowly in both groups. Therefore, the PARP inhibitor reduces the expression of MMP-9 and NF-kappaB and the infiltration of neutrophils in ischemic stroke.
Koh
Seong-Ho
SH
Department of Neurology, Institute of Biomedical Science, College of Medicine, Hanyang University, #17 Haengdang-Dong, Seongdong-gu, Seoul 133-791, Republic of Korea.
Chang
Dae-Il
DI
Kim
Hee-Tae
HT
Kim
Juhan
J
Kim
Myung-Ho
MH
Kim
Kyung Suk
KS
Bae
Inhee
I
Kim
Haekwon
H
Kim
Dong Won
DW
Kim
Seung Hyun
SH
D000818:Animals; D001549:Benzamides / Q000494:pharmacology / Q000627:therapeutic use*; D001921:Brain / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D002545:Brain Ischemia / Q000150:complications* / Q000201:enzymology; D004195:Disease Models, Animal; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis / Q000097:blood*; D016328:NF-kappa B / Q000096:biosynthesis; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D020521:Stroke / Q000188:drug therapy* / Q000201:enzymology / Q000209:etiology; D015854:Up-Regulation
D001549:Benzamides; D016328:NF-kappa B; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; C025160:3-aminobenzamide; D020780:Matrix Metalloproteinase 9