Anti-SENP6 (aa 1-110) polyclonal antibody

Platelets play an important role in cardiovascular thrombosis as well as in many other pathological conditions such as inflammation, atherosclerosis and cancer. While multi-target strategies to treat complex diseases are gaining considerable attention, current development of antiplatelet therapies is mostly oriented towards several single targets, arising from our present understanding of the regulation of platelet activation. Limited efforts to develop multi-target agents or multidrug therapies are mostly due to a lack of a systematic basis to define target combinations with synergistic effects. Here we discuss the perspective to use high content phenotypic screening of in vitro models as a potential source for inference of synergetic multi-target strategies to control platelet activation.

The ethanol-induced toll-like receptor 4 (TLR4) signal activation of microglia and neuroinflammation are observed in both adolescent and adult rat brains, but the regulatory mechanisms of some TLR4 signaling-related factors in this process are still unclear. SUMO-specific protease 6 (SENP6) inhibits neuroinflammation by dampening nuclear factor kappa-B (NF-kappa B) activation via the de-SUMOylation of NF kappa-B essential modulator (NEMO). This study investigates the effects of long-term ethanol consumption on neuroinflammation in the hippocampus of adolescent rats and the regulatory roles of TLR4 and SENP6. Twenty-one days of ethanol exposure in adolescent rats were used to develop an animal model. The number of microglia, microglial activation, and the expression of TLR4 in the hippocampus of adolescent rats were examined by immunoreactivity. The levels of TLR4, activation of NF-kappa B including IkB-alpha and p-NF-kappa B-p65, and SENP6 were measured by western blotting. Proinflammatory cytokines including TNF-alpha, IL-1 beta, and IL-6 were measured by enzyme-linked immunosorbent assay. The NF-kappa B activation and proinflammatory cytokines released in overexpressed SENP6 and siRNA targeting SENP6 microglial cells after treatment with ethanol were estimated in vitro. This study found that alcohol exposure increased the number of activated microglia and the levels of p-NF-kappa B-p65 and proinflammatory cytokines, while it decreased the SENP6 level in wild-type rats, but not in TLR4 knockout rats. The ethanol-induced increases of p-NF-kappa B-p65, TNF-alpha, and IL-1 beta were dampened by overxpression of SENP6 and enhanced in SENP6-siRNA microglia. Our data suggest that ethanol exposure during adolescence induces the microglia-mediated neuroinflammation via TLR4 activation, and SENP6 plays an essential role in dampening NF-kappa B activation and neuroinflammation.