The aim of the present study was to determine the effects of curcumin on antioxidants using a rat model of type 1 diabetes. Seven-week-old male Sprague-Dawley rats were injected with Streptozotocin (STZ) intraperitoneally to induce this model, and then treated with 1.0% curcumin (weight ratio) mixed in their diet for 21 days. The present study included three groups: Control group (NC), diabetic rat model group (DC) and a curcumin treated group (Diab-Cur). The results demonstrated that curcumin treatment markedly decreased the blood glucose levels, plasma malondialdehyde concentration and plasma activity of glutathione peroxidase (GSH-Px) and catalase (CAT); however, it increased the plasma superoxide dismutase (SOD) and insulin levels. Curcumin treatment increased the expression of the CAT, GSH-Px, HO-1 and norvegicus NAD(P)H quinone dehydrogenase 1, and decreased the SOD1 expression, which, led to a diminished oxidative stress status. In addition, curcumin treatment significantly increased the protein expression of Keap1 in the Diab-Cur group when compared with the DC group, decreased cytosolic concentrations of Nrf2 while increasing nuclear accumulation of Nrf2. The results provide evidence that oxidative stress in the STZ-induced diabetic rat model may be attenuated by curcumin via the activation of the Keap1-Nrf2-ARE signaling pathway, as evidenced by a decrease in the blood glucose concentration and an increase in the transcription of several antioxidant genes.

To understand how rabies virus (RV) infection results in neuronal dysfunction, the authors employed proteomics technology to profile host responses to RV infection. In mice infected with wild-type (wt) RV, the expression of proteins involved in ion homeostasis was altered. H(+) ATPase and Na(+)/K(+) ATPase were up-regulated whereas Ca(2+) ATPase was down-regulated, which resulted in reduction of the intracellular Na(+) and Ca(2+) concentrations. Furthermore, infection with wt RV resulted in down-regulation of soluble NSF attachment receptor proteins (SNAREs) such as alpha-synaptosome-associated protein (SNAP), tripartite motif-containing 9 (TRIM9), syntaxin, and pallidin, all of which are involved in docking and fusion of synaptic vesicles to and with presynaptic membrane. As a consequence, accumulation of synaptic vesicles was observed in the presynapses of mice infected with wt RV. These data demonstrate that infection with wt RV results in alteration of host protein expression, particularly those involved in ion homeostasis and docking and fusion of synaptic vesicles to presynaptic membrane, which may lead to neuronal dysfunction. On the other hand, attenuated RV up-regulated the expression of proteins involved in the induction of apoptosis, explaining why apoptosis is observed only in cells or animals infected with attenuated RV in previous studies.

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BackgroundBotulinum neurotoxins are produced by Clostridium botulinum bacteria. There are eight serologically distinct botulinum neurotoxin isoforms (serotypes A–H). Currently, botulinum neurotoxin serotype A (BoNT⁄A) is commonly used for the treatment of many disorders, such as hyperactive musculoskeletal disorders, dystonia, and pain. However, the effectiveness of BoNT⁄A for pain alleviation and the mechanisms that mediate the analgesic effects of BoNT⁄A remain unclear. To define the antinociceptive mechanisms by which BoNT/A functions, the interactions between BoNT⁄A and the transient receptor potential vanilloid subfamily 1 (TRPV1) were investigated using immunofluorescence, co-immunoprecipitation, and western blot analysis in primary mouse embryonic dorsal root ganglion neuronal cultures.Results1) Three-week-old cultured dorsal root ganglion neurons highly expressed transient TRPV1, synaptic vesicle 2A (SV2A) and synaptosomal-associated protein 25 (SNAP-25). SV2A and SNAP-25 are the binding receptor and target protein, respectively, of BoNT⁄A. 2) TRPV1 colocalized with both BoNT⁄A and cleaved SNAP-25 when BoNT⁄A was added to dorsal root ganglia neuronal cultures. 3) After 24 hours of BoNT⁄A treatment (1 nmol⁄l), both TRPV1 and BoNT⁄A positive bands were detected in western blots of immunoprecipitated pellets. 4) Blocking TRPV1 with a specific antibody decreased the cleavage of SNAP-25 by BoNT⁄A.ConclusionBoNT/A interacts with TRPV1 both structurally and functionally in cultured mouse embryonic dorsal root ganglion neurons. These results suggest that an alternative mechanism is used by BoNT⁄A to mediate pain relief.

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