Abstract Background Obesity is one of the principal causative factors involved in development metabolic syndrome. AMP-activated protein kinase (AMPK) an energy sensor that regulates cellular metabolism. The role adipocyte differentiation not completely understood, therefore, we examined effect 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR), a pharmacological activator on 3T3L1 cells and mouse D iet i nduced o besity (DIO) model. Methods To examine AICAR model, were...

S-nitrosylation and S-glutathionylation, redox-based modifications of protein thiols, are recently emerging as important signaling mechanisms. In this study, we assessed S-nitrosylation-based regulation Janus-activated kinase 2/signal transducer activator transcription 3 (JAK2/STAT3) pathway that plays critical roles in immune/inflammatory responses tumorigenesis.Our studies show STAT3 stimulated microglia underwent two distinct redox-dependent modifications, S-glutathionylation. was...

Globoid cell leukodystrophy (Krabbe disease) is characterized by the accumulation of a toxic metabolite, psychosine (galactosylsphingosine), which substrate for deficient enzyme (galactocerebroside beta-galactosidase). This study underscores possible role in effect inducible nitric oxide synthase (iNOS) -derived NO pathophysiology this demyelinating disease. For first time, we provide evidence expression iNOS CNS Krabbe patient and show that iNOS-expressing cells were astrocytes. Psychosine...

Chronic cerebral hypoperfusion (CCH), featuring in most of the Alzheimer's disease spectrum, plays a detrimental role brain amyloid-β (Aβ) homeostasis, cerebrovascular morbidity, and cognitive decline; therefore, early management pathology is considered to be important for intervention impending decline. S-nitrosoglutathione (GSNO) an endogenous nitric oxide carrier modulating endothelial function, inflammation, neurotransmission. Therefore, effect GSNO treatment on CCH-associated...

In the present study a possible role of glycosphingolipids (GSLs) in inducible nitric oxide synthase (iNOS) gene expression and (NO) production after spinal cord injury (SCI) rats has been established. primary rat astrocytes lipopolysaccharide (LPS) interferon-γ (IFN-γ) treatment increased intracellular levels lactosylceramide (LacCer) induced iNOS expression. d -Threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol·HCI (PDMP), glucosylceramide LacCer (galactosyltransferase, GalT-2)...

Abstract Lipopolysaccharide (LPS) and interferon‐γ (IFN) treatment of C6 rat glioma cells increased the intracellular ceramide level expression inducible nitric oxide synthase ( iNOS ) gene. To delineate possible role in induction , we examined source associated signal transduction pathway(s) with use inhibitors generation. The inhibitor neutral sphingomyelinase (3‐ O ‐methylsphingomyelin, MSM) inhibited whereas acidic (SR33557) or that de novo synthesis (fumonisin B1) had no effect on ....

S-nitrosoglutathione (GSNO) is an endogenous nitric oxide (NO) carrier that plays a critical role in redox based NO signaling. Recent studies have reported GSNO regulates the activities of STAT3 and NF-κB via S-nitrosylation dependent mechanisms. Since are key transcription factors involved tumor progression, chemoresistance, metastasis head neck cancer, we investigated effect cell culture mouse xenograft models squamous carcinoma (HNSCC). For studies, three HNSCC lines were tested (SCC1,...

Abstract Previous studies have described that statins (inhibitors of cholesterol and isoprenoid biosynthesis) inhibit the output amyloid‐β (Aβ) in animal model thus decrease risk Alzheimer’s disease. However, their action mechanism(s) Aβ precursor protein (APP) processing generation is not fully understood. In this study, we report lovastatin treatment reduced cultured hippocampal neurons as a result APP levels β‐secretase activities low density Lubrol WX (non‐ionic detergent) extractable...

In rat glial cells the lipopolysaccharide (LPS)-induced inducible nitric oxide synthase (iNOS) gene expression was enhanced by extracellular glucose concentration in a dose-dependent manner. On other hand, 2-deoxy-d-glucose decreased LPS-induced iNOS even presence of (6 gm/l), suggesting that metabolism is linked to regulation expression. The intracellular NADPH/NADP+ directly correlated with concentration, and reduction NADPH generation via block glucose-6-phosphate dehydrogenase (G6PD)...

Recent studies report that loss and dysfunction of mitochondria peroxisomes contribute to the myelin axonal damage in multiple sclerosis (MS). In this study, we investigated efficacy a combination lovastatin AMP-activated protein kinase (AMPK) activator (AICAR) on spinal cords, relative clinical disease symptoms, using mouse model experimental autoimmune encephalomyelitis (EAE, for MS). We observed AICAR treatments individually provided partial protection mitochondria/peroxisomes...

Asymmetric dimethylarginine (ADMA), an endogenous inhibitor and uncoupler of nitric oxide synthase, has gained attention as a risk factor for cardiac disease, metabolic syndrome, cerebrovascular disease. In this study, we investigated the role systemic ADMA overburden in cerebromicrovascular pathology associated with cognitive dysfunction using APPSwDI transgenic mice expressing human β-amyloid precursor protein Swedish (Tg-SwDI), model β-amyloidosis. To induce ADMA, Tg-SwDI were treated...

Abstract The present study underlines the importance of phospholipase A 2 (PLA )‐ and lipoxygenase (LO)‐mediated signaling processes in regulation inducible nitric oxide synthase (iNOS) gene expression. In glial cells, lipopolysaccharide (LPS) induced activities PLA (calcium‐independent ; iPLA cytosolic cPLA ) as well expression iNOS. inhibition by methyl arachidonyl fluorophosphates (MAFP) or antisense oligomer against bromoenol lactone reduced LPS‐induced iNOS NFκB activation. addition, LO...