Original ContributionRole of 12/15-lipoxygenase in nitrosative stress and peripheral prediabetic and diabetic neuropathies
Section snippets
Reagents
Unless otherwise stated, all chemicals were of reagent-grade quality and were purchased from Sigma Chemical (St. Louis, MO, USA). Cinnamyl-3,4-dihydroxy-α-cyanocinnamate (CDC) was obtained from Enzo Life Sciences International (Plymouth Meeting, PA, USA). Mouse monoclonal (clone 1A6) anti-nitrotyrosine (NT) antibody for Western blot analysis of nitrated proteins was purchased from Millipore (Billerica, MA, USA). Rabbit polyclonal (clone H-100) anti-LO antibody for Western blot analysis was
Results
In experiment 1, LO fluorescence was clearly identifiable in endothelial (Fig. 1a) and Schwann (Fig. 1b) cells of mouse sciatic nerve.
In experiment 2, the initial (before STZ administration) body weights were similar in all experimental groups (Table 1). Weight gain during the 16-week study was lower in both untreated and CDC-treated diabetic mice than in the nondiabetic control group. CDC treatment did not affect weight gain in either control or diabetic mice. Initial (after STZ
Discussion
It has been known for at least a decade that diabetes is associated with disturbances in arachidonic acid metabolism in peripheral nerve [35]. Arachidonic acid is metabolized by cyclooxygenases (COX)-1 and -2, 5- and 12/15-LOs, and cytochrome P450 epoxygenase. Diabetes does not affect rat sciatic nerve COX-1 expression, and the findings with the nonselective COX inhibitor flurbiprofen suggest that COX-1 is essentially required for normal peripheral nerve function [36]. In contrast, sciatic
Acknowledgments
The study was supported by National Institutes of Health Grants DK074517 and DK077141 and American Diabetes Association Research Grant 7-08-RA-102 (both to I.G.O.). The Cell Biology and Bioimaging Core utilized in this work is supported in part by COBRE (NIH P20 RR021945) and CNRU (NIH 1P30-DK072476) center grants from the National Institutes of Health. The authors thank Drs. Douglas E. Wright from the University of Kansas Medical Center (Kansas City, KS, USA) and Gary L. Pittenger from Eastern
References (80)
- et al.
12-Lipoxygenase metabolism in mouse distal convoluted tubule cells
Kidney Int.
(2005) - et al.
Ceramide elevates 12-hydroxy-eicosatetraenoic acid levels and upregulates 12-lipoxygenase in rat primary hippocampal cell cultures containing predominantly astrocytes
Neurochem. Int.
(2008) - et al.
Activation of mitogen-activated protein kinases by arachidonic acid and its metabolites in vascular smooth muscle cells
J. Biol. Chem.
(1994) - et al.
The oxidized lipid and lipoxygenase product 12(S)-hydroxyeicosa-tetraenoic acid induces hypertrophy and fibronectin transcription in vascular smooth muscle cells via p38 MAPK and cAMP response element-binding protein activation: mediation of angiotensin II effects
J. Biol. Chem.
(2002) - et al.
Inflammation and immune regulation by 12/15-lipoxygenases
Prog. Lipid Res.
(2006) - et al.
Differential behavior of mesangial cells derived from 12/15-lipoxygenase knockout mice relative to control mice
Kidney Int.
(2003) - et al.
Effects of silencing leukocyte-type 12/15-lipoxygenase using short interfering RNAs
J. Lipid Res.
(2005) - et al.
12/15-Lipoxygenase activity mediates inflammatory monocyte/endothelial interactions and atherosclerosis in vivo
J. Biol. Chem.
(2004) Diabetic painful and insensate neuropathy: pathogenesis and potential treatments
Neurotherapeutics
(2009)- et al.
Transgenic mice overexpressing aldose reductase in Schwann cells show more severe nerve conduction velocity deficit and oxidative stress under hyperglycemic stress
Mol. Cell Neurosci.
(2003)
Evening primrose oil treatment corrects reduced conduction velocity but not depletion of arachidonic acid in nerve from streptozotocin-induced diabetic rats
Prostaglandins Leukot. Essent. Fatty Acids
Effect of α-lipoic acid on vascular responses and nociception in diabetic rats
Free Radic. Biol. Med.
Effect of the NAD(P)H oxidase inhibitor, apocynin, on peripheral nerve perfusion and function in diabetic rats
Life Sci.
Treatment with the xanthine oxidase inhibitor, allopurinol, improves nerve and vascular function in diabetic rats
Eur. J. Pharmacol.
SOD2 protects neurons from injury in cell culture and animal models of diabetic neuropathy
Exp. Neurol.
Dityrosine cross-linking promotes formation of stable alpha-synuclein polymers: implication of nitrative and oxidative stress in the pathogenesis of neurodegenerative synucleinopathies
J. Biol. Chem.
Nitration of tau protein is linked to neurodegeneration in tauopathies
Am. J. Pathol.
Effects of the peroxynitrite decomposition catalyst, FeTMPyP, on function of corpus cavernosum from diabetic mice
Eur. J. Pharmacol.
Lipoxygenases and lipid signaling in vascular cells in diabetes
Front. Biosci.
Lipid inflammatory mediators in diabetic vascular disease
Arterioscler. Thromb. Vasc. Biol.
12-Lipoxygenase-knockout mice are resistant to inflammatory effects of obesity induced by Western diet
Am. J. Physiol. Endocrinol. Metab.
12/15-Lipoxygenase products induce inflammation and impair insulin signaling in 3T3-L1 adipocytes
Obesity (Silver Spring)
12/15-Lipoxygenase regulates intercellular adhesion molecule-1 expression and monocyte adhesion to endothelium through activation of RhoA and nuclear factor-kappaB
Arterioscler. Thromb. Vasc. Biol.
Disparate effects of 12-lipoxygenase and 12-hydroxy-eicosatetraenoic acid in vascular endothelial and smooth muscle cells and in cardiomyocytes
Arch. Physiol. Biochem.
Role of 12-lipoxygenase in the stimulation of p38 mitogen-activated protein kinase and collagen alpha5(IV) in experimental diabetic nephropathy and in glucose-stimulated podocytes
J. Am. Soc. Nephrol.
Novel interactions between TGF-β1 actions and the 12/15-lipoxygenase pathway in mesangial cells
J. Am. Soc. Nephrol.
12/15-Lipoxygenase regulates the inflammatory response to bacterial products in vivo
J. Immunol.
Novel lipoxygenase inhibitors as neuroprotective reagents
J. Neurosci. Res.
Vitamin K prevents oxidative cell death by inhibiting activation of 12-lipoxygenase in developing oligodendrocytes
J. Neurosci. Res.
Signaling mechanisms of nuclear factor-kappaB-mediated activation of inflammatory genes by 13-hydroperoxyoctadecadienoic acid in cultured vascular smooth muscle cells
Arterioscler. Thromb. Vasc. Biol.
Effects of cholesterol-tagged small interfering RNAs targeting 12/15-lipoxygenase on parameters of diabetic nephropathy in a mouse model of type 1 diabetes
Am. J. Physiol. Ren. Physiol.
Critical role of macrophage 12/15-lipoxygenase for atherosclerosis in apolipoprotein E-deficient mice
Circulation
5-Lipoxygenase, but not 12/15-lipoxygenase, contributes to degeneration of retinal capillaries in a mouse model of diabetic retinopathy
Diabetes
American Diabetes Association. Diabetic neuropathies: a statement by the American Diabetes Association
Diab. Care
Role of poly(ADP-ribose) polymerase activation in diabetic neuropathy
Diabetes
High-fat diet induced neuropathy of pre-diabetes and obesity: effects of "healthy" diet and aldose reductase inhibition
Diabetes
Inducible nitric oxide synthase gene deficiency counteracts multiple manifestations of peripheral neuropathy in a streptozotocin-induced mouse model of diabetes
Diabetologia
Peripheral neuropathy in mice with neuronal nitric oxide synthase gene deficiency
Int. J. Mol. Med.
Hyperglycemia alters the Schwann cell mitochondrial proteome and decreases coupled respiration in the absence of superoxide production
J. Proteome Res.
Oxidative–nitrosative stress and poly(ADP-ribose) polymerase (PARP) activation in experimental diabetic neuropathy: the relation is revisited
Diabetes
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