Nuclear hormone receptors (NHRs) play vital roles in the regulation of metabolism, reproduction, and development. We found that inactivation of a C. elegans HNF4 homologue nhr-64 by RNA interference (RNAi) suppresses low fat stores in stearoyl-CoA desaturase-deficient fat-6;fat-7 double mutants and sterol regulatory element binding protein (SREBP) sbp-1 mutants. Furthermore, inactivation of nhr...

Purified bovine rhodopsin was reconstituted into vesicles consisting of 1-stearoyl-2-oleoyl phosphatidylcholine or 1-stearoyl-2-docosahexaenoyl phosphatidylcholine with and without 30 mol % cholesterol. Rhodopsin stability was examined using differential scanning calorimetry (DSC). The thermal unfolding transition temperature (T(m)) of rhodopsin was scan rate-dependent, demonstrating the presen...

Cell-mediated lympholysis (CML) 1 has been generated in vitro against trinitrophenyl (TNP)-modified syngeneic murine spleen cells (1). The specificity of the effectors generated is such that the stimulater and target cells must beth be modified by the same agent (2, 3)1 and must also express the same H-2K and/or H-2D haplotypes (4, 5). In previous studies of the specificity of the CML effecters...

The combined use of several drugs targeting different cellular functions is one approach to achieve tumor control in cancer. We studied the effects of Pseudomonas exotoxin A (PE)-based immunotoxins (ITs), the 9.2.27PE and the 425.3PE, together with 2 different triphenylmethyl derivatives, triphenylmethyl phosphonates and phosphonochloridates (TPMP)-I-2 and 4BI. Combining the triphenylmethyl der...

TABLE I Conversion of stearoyl-I -W-CoA to sphingonayelin The incubation mixtures in Part A contained 100 pmoles of potassium phosphate buffer, pH 7.8,80 mpmoles of stearoyl-I-‘4C-CoA (67,600 cpm), 2 pmoles of ATP, 2 rmoles of MgClz, and resuspended rat brain particulate preparations in a final volume of 1.18 ml. In Part B, the components of the mixtures were the same except that 1.0 ml of 100,...

Increased de novo lipogenesis is one of the major metabolic events in cancer. In human hepatocellular carcinoma (HCC), de novo lipogenesis has been found to be increased and associated with the activation of AKT/mTOR signaling. In mice, overexpression of an activated form of AKT results in increased lipogenesis and hepatic steatosis, ultimately leading to liver tumor development. Hepatocarcinog...

Stearoyl-CoA desaturase 1 (SCD1) is an established molecular target in many primary tumors including breast, lung, pancreatic, colon and hepatocellular carcinomas. However, its potential role in supporting endometrial cancer growth and progression has not yet been determined. In this study, we evaluated the value of SCD1 as a candidate therapeutic target in human endometrial cancer. Compared wi...

We previously described 3 bioactive oxidation products of 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine (PAPC) containing oxovaleroyl (POVPC), glutaroyl (PGPC), and epoxyisoprostane (PEIPC) groups at the sn-2 position that were increased in minimally modified/oxidized low density lipoprotein (MM-LDL) and rabbit atherosclerotic lesions. We demonstrated specific and contrasting effect...

Mammalian Delta9 stearoyl-CoA desaturase 1 (SCD1) is a key enzyme in the biosynthesis of mono-unsaturated fatty acids in the endoplasmic reticulum (ER). It is a short-lived multispanning ER membrane protein, reported to be degraded by the ubiquitin-proteasome-independent pathway. We have examined SCD1 protein degradation using cultured mammalian cells. Exogenously expressed SCD1 in CHO-K1 cells...

Previous studies showed that mice deficient in Scd1 had a reduced level of liver triglyceride and an improvement in insulin sensitivity. We studied Scd1(-/-) mice on a very low-fat, high-carbohydrate lipogenic diet. The animals were almost entirely devoid of high-density lipoprotein (HDL). Nonetheless, they were hypercholesterolemic and had cholestasis. These changes were reversible with oil co...