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drug development
targeting insect SCP-2 may be a viable approach for the development of insecticides
SCP2 is a binding protein for endocannbinoids N-arachidonylethanolamine and 2-arachidonoylglycerol. N-arachidonylethanolamine and 2-arachidonoylglycerol associate with SCP2 at a putative cholesterol binding pocket with DeltaG values of ?3.6 and ?4.6 kcal per mol, respectively. SCP2-mediated transfer of cholesterol in vitro is inhibited by micromolar concentrations of N-arachidonylethanolamine, and heterologous expression of SCP2 in HEK-293 cells increases time-related accumulation of N-arachidonylethanolamine in a temperature-dependent fashion
SCP2 is a critical host factor for dengue virus production in mosquito Aag2 cells. Treatment with inhibitor SCPI-1, or knockdown of SCP2 dramatically represses the virus production in mosquito but not mammalian cells.The intracellular cholesterol distribution in mosquito cells is altered by SCP2 inhibitor treatment, suggesting that SCP2-mediates cholesterol trafficking pathway that is important for dengue virus viral production. SCPI-1 treatment decreases cholesterol in both mammalian and mosquito cell lines, but this decrease in cholesterol only leads to a decline in viral titer in mosquito host cells
wild-type mice fed a cholesterol-rich diet show increased weight gain, hepatic lipid, and bileacid accumulation. SCP-2 overexpression further exacerbates hepatic lipid accumulation in cholesterol-fed females and males. Primarily in female mice, hepatic cholesterol accumulation induced by SCP-2 overexpression is associated with increased levels of LDL receptor, HDL-receptor scavenger receptor SR-B1, liver fatty acid binding protein L-FABP, and 3alpha-hydroxysteroid dehydrogenase, without alteration of other proteins involved in cholesterol uptake, esterification, efflux, or oxidation/transport of bile salts. The effects of SCP-2 overexpression and cholesterol-rich diet are downregulation of proteins involved in cholesterol transport like L-FABP and SR-B1, cholesterolsynthesis related to sterol regulatory element binding protein 2 and HMG-CoA reductase, and bile acid oxidation/transport
although SCP-2 was established as a protein that transfers cholesterol and phospholipids decades ago, recent findings with lipid rafts/caveolae and SCP-2 suggest that they may provide a conceptual link to metabolic processes that might be regulated through the respective signaling pathways
Results 1 - 5 of 5