Effect of 3-aminobenzamide, PARP inhibitor, on matrix metalloproteinase-9 level in plasma and brain of ischemic stroke model

Koh, Seong‐Ho; Chang, Dae-Il; Kim, Hee-Tae; Kim, Juhan; Kim, Myung Ho; Kim, Kyung Suk; Bae, Inhee; Kim, Haekwon; Kim, Dong Won; Kim, Seung Hyun

doi:10.1016/j.tox.2005.06.023

Cited by 54 publications

(50 citation statements)

References 32 publications

(77 reference statements)

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“…Similarly, Audebert et al[ 5] showed that acute-phase responses such as higher leukocyte count, body temperature and fibrinogen concentration 12 h after onset of neurological deficit are potential predictors of early progression in lacunar stroke. In our previous study, we found that MMP-9 plays very important roles in inflammation induced by ischemic stroke [8, 18]. In this study, elevation of MMP-9 and ESR might be caused by nuclear factor ĸB, considering our previous in vivo results that show that nuclear factor ĸB plays an important role in the elevation of MMP-9 [8], and increased MMP-9 is related with other inflammatory profiles.…”

Section: Discussionmentioning

confidence: 51%

“…In our previous study, we found that MMP-9 plays very important roles in inflammation induced by ischemic stroke [8, 18]. In this study, elevation of MMP-9 and ESR might be caused by nuclear factor ĸB, considering our previous in vivo results that show that nuclear factor ĸB plays an important role in the elevation of MMP-9 [8], and increased MMP-9 is related with other inflammatory profiles.…”

Section: Discussionmentioning

confidence: 51%

“…Samples were centrifuged at 1,500 rpm for 5 min, and plasma was subsequently isolated and stored at –70°C until assayed for MMP. Western blotting was performed as previously described [8]. All zymographic results were repeated twice and further confirmed by repeating the experiments twice.…”

Section: Methodsmentioning

confidence: 99%

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The Role of Matrix Metalloproteinase 9 in Early Neurological Worsening of Acute Lacunar Infarction

Kim¹,

Lee²,

Koh³

et al. 2006

Eur Neurol

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The involvement of matrix metalloproteinases (MMPs) in ischemic-stroke-induced inflammatory response has recently been suggested; however, the relationship between MMPs and stroke progression has not been evaluated. We investigated the role of MMPs in neurological worsening of acute lacunar infarction. Forty-nine consecutive patients with an acute lacunar infarction (as defined by clinical and MRI criteria within 48 h after stroke onset) were evaluated. Clinical, biochemical, rheological, inflammatory and other parameters were compared between progressive and nonprogressive groups. Among the variables, only inflammatory parameters, including MMP-9 and erythrocyte sedimentation rate, were associated with neurological worsening of acute lacunar infarction (p < 0.05). These results suggest that the inflammatory process could play an important role in early neurological worsening of acute lacunar infarction.

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Section: Discussionmentioning

confidence: 51%

Section: Discussionmentioning

confidence: 51%

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The Role of Matrix Metalloproteinase 9 in Early Neurological Worsening of Acute Lacunar Infarction

Kim¹,

Lee²,

Koh³

et al. 2006

Eur Neurol

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“…MMPs have been implicated in metastases because of its role in the degradation of basement membrane collagen [21,53] . Koh et al [19] have already shown that PARP inhibition with the relatively less potent inhibitor 3-aminobenzamide diminishes the expression of the MMP-9 protein and infiltration of neutrophils in a rat model of ischemic stroke. Similarly, Kauppinen and Swanson [49] have suggested that PARP activation is required for the neurotoxicity resulting from TNF-␣ -induced release of MMP-9.…”

Section: Discussionmentioning

confidence: 97%

“…More recently, overactivation of PARP has been shown to be involved in the regulation of inflammatory processes, with some inhibitors of PARP showing anti-inflammatory effects in animal models, particularly those of acute inflammation [14][15][16][17][18] . This pro-inflammatory effect of PARP is associated with some transcription factors, particularly nuclear factor (NF)-B [19][20][21] . A recent report has shown that PARP inhibitors affect NF-B activation and gene expression via the activation of the PI 3 -kinase/ Akt (protein kinase B) pathway, which can inhibit mitogen-activated protein kinase activation for example [22] .…”

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confidence: 99%

Poly(ADP-Ribose) Polymerase Inhibition Down-Regulates Expression of Metastasis-Related Genes in CT26 Colon Carcinoma Cells

Threadgill

Wang

et al. 2009

Pathobiology

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Objectives: The current study was designed to test the hypothesis that inhibition of poly(ADP-ribose) polymerase in colorectal cancer mediates down-regulation of metastasis-related gene expression through the regulation of nuclear factor-κB (NF-κB) activity. Methods: Mouse colon carcinoma cells (CT26) were treated with and without the PARP inhibitor 5-aminoisoquinolin-1(2H)-one hydrochloride (5-AIQ). We investigated adhesion, migration and invasion of differently treated CT26 cells. In addition, the expression levels of PARP, NF-κB, integrin β₁, MMP-9 and MMP-2 as well as the activities of NF-κB, MMP-9 and MMP-2 were determined by Western blot, electrophoretic mobility gel shift assay and zymography, respectively. Results: Inhibition ofPARP attenuated the adhesion of CT26 cells to the extracellular matrix and their migration and invasion through Matrigel. In addition, the results of Western blot showed that the expression levels of PARP, NF-κB, integrin β₁, MMP-9 and MMP-2 were reduced in 5-AIQ-treated CT26 cells; the activities of NF-κB, MMP-9 and MMP-2 were also suppressed. Conclusions: Inhibition of PARP down-regulates the expression of metastasis-related genes in mouse colon carcinoma cells. This could be, at least in part, through the regulation of NF-κB activity, but the precise mechanisms of action remain to be elucidated.

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Adoptive regulatory T‐cell therapy protects against cerebral ischemia

Gan

Sun

et al. 2013

Annals of Neurology

262

289

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OBJECTIVES Recent evidence suggests that functional deficiency in regulatory T cells (Tregs), an innate immuno-modulator, exacerbates brain damage after cerebral ischemia. We therefore evaluated the effect of Treg transfer in rodent models of ischemic stroke and further investigated the mechanism underlying Treg-afforded neuroprotection. METHODS We examined the therapeutic potential of Tregs and the mechanisms of neuroprotection in vivo in 2 rodent models of ischemic stroke and in vitro in Treg-neutrophil co-cultures using a combined approaches including cell-specific depletion, gene knockout mice, and bone marrow chimeras. RESULTS Systemic administration of purified Tregs at 2, 6 or even 24 hours after MCAO resulted in a marked reduction of brain infarct and prolonged improvement of neurological functions lasting out to 4 weeks. Treg-afforded neuroprotection was accompanied by attenuated blood-brain barrier (BBB) disruption during early stages of ischemia, decreased cerebral inflammation and reduced infiltration of peripheral inflammatory cells into the lesioned brain. Surprisingly, Tregs exerted early neuroprotection without penetrating into the brain parenchyma or inhibiting the activation of residential microglia. Rather, both in vivo and in vitro studies demonstrated that Tregs suppressed peripheral neutrophil-derived matrix metallopeptidase-9 production, thus preventing proteolytic damage of the BBB. In additions to its potent central neuroprotection, Treg treatment was shown to ameliorate post-stroke lymphopenia, suggesting a beneficial effect on immune status. INTERPREATION Our study suggests that Treg adoptive therapy is a novel and potent cell-based therapy targeting post-stroke inflammatory dysregulation and neurovascular disruption.

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Effect of 3-aminobenzamide, PARP inhibitor, on matrix metalloproteinase-9 level in plasma and brain of ischemic stroke model

Cited by 54 publications

References 32 publications

The Role of Matrix Metalloproteinase 9 in Early Neurological Worsening of Acute Lacunar Infarction

The Role of Matrix Metalloproteinase 9 in Early Neurological Worsening of Acute Lacunar Infarction

Poly(ADP-Ribose) Polymerase Inhibition Down-Regulates Expression of Metastasis-Related Genes in CT26 Colon Carcinoma Cells

Adoptive regulatory T‐cell therapy protects against cerebral ischemia

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