Contribution of Aldose Reductase to Diabetic Hyperproliferation of Vascular Smooth Muscle Cells

Srivastava, Sanjay; Ramana, Kota V.; Tammali, Ravinder; Srivastava, Satish K.; Bhatnagar, Aruni

doi:10.2337/diabetes.55.04.06.db05-0932

Cited by 60 publications

(71 citation statements)

References 56 publications

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“…Low bone turnover has also been associated with vascular calcification in diabetic HD patients (Galassi et al, 2006), and poor glycemic control induces low bone turnover by suppressing PTH secretion (Sugimoto et al, 1990), impairing osteoblast growth (Inaba et al, 1999), and reducing the responsiveness of osteoblasts to PTH and 1,25-dihydroxyvitamin D3 (Inaba et al, 1999). A direct adverse effect of high glucose on vascular cells has also been proposed (Wadham et al, 2007;Srivastava et al, 2006).…”

Section: Discussionmentioning

confidence: 96%

Association of glycated albumin, but not glycated hemoglobin, with peripheral vascular calcification in hemodialysis patients with type 2 diabetes

et al. 2008

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Section: Discussionmentioning

confidence: 96%

Association of glycated albumin, but not glycated hemoglobin, with peripheral vascular calcification in hemodialysis patients with type 2 diabetes

et al. 2008

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“…The role of AR in the mediation of oxidative stress-induced signaling was further confirmed in an animal model of restenosis. Restenosis of balloon -injured rat carotid arteries was significantly blocked by AR inhibitors [18,23]. Recently, we have shown that GS-DHN formed by the reduction of GS-HNE by AR could mediate cell signaling leading to activation of NF-κB and proliferation of cultured VSMC [24].…”

Section: Introductionmentioning

confidence: 99%

Mediation of aldose reductase in lipopolysaccharide-induced inflammatory signals in mouse peritoneal macrophages

Ramana

2006

Cytokine

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Aldose reductase (AR; AKR1B1) a member of aldoketo reductase super family, that we had shown earlier mediates cytotoxic signals induced by high glucose, cytokines and growth factors, also mediates the inflammatory signals induced by Gram-negative bacterial endotoxin, lipopolysaccharide (LPS). Inhibition of AR by three distinct AR inhibitors sorbinil, tolrestat or zopolrestat suppressed the LPS-induced production of inflammatory cytokines such as TNF-α, IL-6, IL-1β, IFN-γ, and chemokine MCP-1 in murine peritoneal macrophages. Inhibition of AR also prevented the production of nitric oxide, and prostaglandin E2 and expression of iNOS and Cox-2 proteins. The LPS-induced DNA binding activity of NF-κB and AP1 were significantly inhibited by AR inhibitors, and this effect was mediated through the inhibition of phosphorylation of IκB-α, IKK α/β and PKC. These results suggest the therapeutic use of AR inhibitors as anti-inflammatory drugs.

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“…The third limitation concerns another possible route of HG-related cellular damage, namely the polyol pathway. We were unable to find reports on the effects of NAC in the modulation of polyol-related metabolism [32, 33]. Such investigations could provide additional options with therapeutic implications [34].…”

Section: Discussionmentioning

confidence: 99%

N-Acetylcysteine-Mediated Antioxidation Prevents Hyperglycemia-Induced Apoptosis and Collagen Synthesis in Rat Mesangial Cells

Hung

Liu

Kao³

et al. 2008

Am J Nephrol

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Background/Aims: High-glucose (HG)-induced mesangial apoptosis and fibrogenesis possibly involves reactive oxygen species (ROS) formation and activated mitochondrial stress. We investigated the therapeutic effect of the antioxidant N-acetylcysteine (NAC) on cellular apoptosis and matrix accumulation in HG-treated rat mesangial cells (RMCs). Methods: RMCs were cultured in media containing 5 (control) or 35 mM (HG) glucose. Cellular apoptosis was assayed by TdT-mediated dUTP nick-end labeling staining. Collagen and transforming growth factor-1 gene expression were measured by reverse transcriptase-polymerase chain reaction or Northern blotting. Mitochondrial capacity and intracellular ROS generation was assayed by fluorescence microscopy and flow cytometry, respectively. Cellular ATP production and malondialdehyde (MDA) formation were determined by a luciferin-luciferase reaction and high-performance liquid chromatography, respectively. Cytochrome c release, caspase activation and poly(ADP)ribose polymerase cleavage were assayed by Western blotting. Results: HG-treated RMCs displayed enhanced cellular apoptosis (65%) and collagen gene expression (1.8-fold increase); these reactions could be significantly suppressed by 1 mM NAC (p < 0.05). Intracellular ROS generation, production of ATP and MDA, and caspase-3, -8 and -9 activities were significantly increased in HG-treated RMCs, and were effectively attenuated by addition of NAC. Conclusion: It is concluded that NAC prevents HG-induced mesangial apoptosis and fibrogenesis pathways by the reduction of oxidative stress.

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Contribution of Aldose Reductase to Diabetic Hyperproliferation of Vascular Smooth Muscle Cells

Abstract: The objective of this study was to determine whether the polyol pathway enzyme aldose reductase mediates diabetes abnormalities in vascular smooth muscle cell (

Cited by 60 publications

References 56 publications

Association of glycated albumin, but not glycated hemoglobin, with peripheral vascular calcification in hemodialysis patients with type 2 diabetes

Association of glycated albumin, but not glycated hemoglobin, with peripheral vascular calcification in hemodialysis patients with type 2 diabetes

Mediation of aldose reductase in lipopolysaccharide-induced inflammatory signals in mouse peritoneal macrophages

N-Acetylcysteine-Mediated Antioxidation Prevents Hyperglycemia-Induced Apoptosis and Collagen Synthesis in Rat Mesangial Cells

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