Disease relevance of SCD

• Taken together, these results suggest that SCD protein and activity levels are associated with the events of neoplastic cell transformation and programmed cell death [1].
• In the absence of SCD1, stearate promotes oxidation, leading to protection from saturated fat-induced obesity [2].
• High stearoyl-CoA desaturase protein and activity levels in simian virus 40 transformed-human lung fibroblasts [1].
• These results indicate that loss of SCD expression is a frequent event in prostate adenocarcinoma, and further supports a role for altered lipid metabolism as a factor in the process of carcinogenesis [3].
• Relationship between stearoyl-CoA desaturase activity and plasma triglycerides in human and mouse hypertriglyceridemia [4].
• SCD expression in adipose tissue is independently regulated by weight loss and by carbohydrate and saturated fat intakes [5].

Psychiatry related information on SCD

• Efforts to create more awareness of SCD are paradoxically increasing frustration and stigmatization in the absence of a commensurate improvement of services [6].
• Self-efficacy is not associated with demographic factors, but is predicted by physical symptoms, while different aspects of self-management are predicted by age (responsibility with care), educational level (independence and confidence with care) and psychological symptoms (knowledge about SCD and confidence with care) [7].
• Significant portions of the variance in adjustment were accounted for by stress appraisal (19%), expectations of efficacy (9%) and health locus of control (9%) for children with CF and by stress appraisal (21%) and self-worth (12%) for children with SCD [8].
• The predictive value of D5D activity was independent of lifestyle factors (smoking, BMI and physical activity), whereas the risk associated with higher SCD-1 and D6D activities was mainly explained by obesity [9].

High impact information on SCD

• Critical role of stearoyl-CoA desaturase-1 (SCD1) in the onset of diet-induced hepatic insulin resistance [10].
• Chk2 activation is initiated by phosphorylation of Thr68, in the serine-glutamine/threonine-glutamine cluster domain (SCD), by ATM [11].
• Stearoyl-CoA desaturase (SCD) is a key regulator of membrane fluidity, turns over rapidly, and represents a model for selective degradation of short-lived proteins of the endoplasmic reticulum (ER) [12].
• Unlike wild-type mice, SCD1-deficient mice failed to elevate the hepatic triglyceride monounsaturated acid (MUFA)/saturated fatty acid (SFA) ratio despite induction of the SCD2 gene [13].
• In addition, SCD1 deficiency also increased plasma high-density lipoprotein cholesterol levels induced by LXR activation [13].

Chemical compound and disease context of SCD

• Inhibition of stearoyl-CoA desaturase activity by the cis-9,trans-11 isomer and the trans-10,cis-12 isomer of conjugated linoleic acid in MDA-MB-231 and MCF-7 human breast cancer cells [14].
• However, high SCD activity has been implicated in diabetes, obesity, atherosclerosis, and cancer in several animal models; therefore, the role that de novo oleate plays in these disease states has to be carefully evaluated [15].
• The Sudden Cardiac Death Heart Failure Trial (SCD HEFT) is testing the implantable cardioverter defibrillator (ICD) against amiodarone and placebo [16].
• Lung hydroxyproline, an index of fibrosis, in SCD, SPD, BCD and BPD were 830, 804, 1609, 1235 micrograms/lung, respectively [17].
• Erythropoietin is being used more widely in the management of sickle cell disease (SCD, inclusive of homozygous sickle beta, SS, and compound heterozygous sickle beta thalassemia, Sbeta0 thal), often in conjunction with hydroxyurea (HU) [18].

Biological context of SCD

• However, the effects of insulin-sensitizing drugs on SCD gene expression and desaturase activities are unknown in humans [19].
• Fatty acid desaturases such as steaoryl-CoA desaturase (SCD) convert saturated to unsaturated fatty acids and are involved in lipogenesis [19].
• The strong correlation of high levels of MUFA and neoplastic phenotype suggest that the regulation of stearoyl CoA desaturase (SCD) must play a significant role in cancer development [1].
• The increase in SCD mRNA expression was preceded by a marked increase in Smad2 phosphorylation in TGF-beta-treated human retinal pigment epithelial cells [20].
• The human homologue, SCD, maps to a region of chromosome 10 linked to type 2 diabetes, and SCD activity correlates with insulin sensitivity [21].

Anatomical context of SCD

• SCD activity led to an increased content of plasma membrane monounsaturated fatty acids (18:1) at the expense of saturated fatty acids (18:0) [22].
• Levels of PPARalpha, PPARgamma, LXRalpha, SCD and ABCA1 mRNAs were similar in macrophages from subjects with T2DM and controls [23].
• SCD gene expression in adipose tissue was determined in 23 subjects, and in a representative subgroup (n = 10) we assessed fatty acid composition in fasting plasma triglycerides to estimate SCD and delta6- and delta5-desaturase activity, using product-to-precursor indexes [19].
• In this study, the levels of SCD protein and activity were investigated in normal (WI38) and SV40-transformed (SV40-WI38) human lung fibroblasts [1].
• TGF-beta also increased SCD mRNA expression in several other cell lines tested [20].

Associations of SCD with chemical compounds

• As shown by confocal microscopy, SCD overexpression led to a decrease of Triton X-100-resistant domains in the plasma membrane, indicating a decrease in membrane-ordered regions [22].
• The SCD inhibitors conjugated linoleic acid and troglitazone nearly abolished ABCA1 destabilization by palmitate and stearate but not by linoleate [24].
• SCD mRNA expression increased by 48% after rosiglitazone (P < 0.01) [19].
• Stearoyl-CoA desaturase (SCD) is a regulatory enzyme involved in the synthesis of the monounsaturated fatty acids palmitoleate and oleate [25].
• Differential display analysis of retinal pigment epithelial (ARPE-19) cells identified SCD as a gene regulated by retinoic acid [25].

Regulatory relationships of SCD

• In mature adipocytes, PPAR gamma stimulation inhibits stearoyl-CoA desaturase 1 (SCD1) enzyme activity resulting in a change of cell membrane fatty acid composition [26].
• In addition, overexpression of active SREBP-1 directly stimulated SCD-1 and FAS [27].

Other interactions of SCD

• Rosiglitazone increases indexes of stearoyl-CoA desaturase activity in humans: link to insulin sensitization and the role of dominant-negative mutation in peroxisome proliferator-activated receptor-gamma [19].
• TGF-beta did not induce SCD mRNA expression in a Smad4-deficient cell line [20].
• The cytochrome b5 genes were not induced at 6 degrees C and their response to ABA was relatively slow compared with fatty acid desaturase genes [28].
• Thus, reduced contents of free fatty acids, acyl-CoAs and ceramides as well as increased AMPK phosphorylation, might contribute to increased insulin sensitivity observed in muscle of SCD1-/- mice [29].
• Herein, we show that the lipogenic gene, stearoyl-CoA desaturase 1 (SCD1), is robustly up-regulated in skeletal muscle from extremely obese humans [30].

Analytical, diagnostic and therapeutic context of SCD

• Two SCD transcripts of 3.9 and 5.2 kilobases in size were found to be expressed in these cells by Northern blot analysis [25].
• Serial deletion and point mutation analyses in reporter gene assays, as well as a gel mobility shift assay, identified an LXR response element in the mouse SCD1 promoter [13].
• A segment of 712 bases coding for part of the human stearoyl-CoA desaturase gene was made by polymerase chain reaction (PCR) using primers based on published rat cDNA sequences [31].
• Site-directed mutagenesis of binding sites in this region identified the CCAAT box as the critical cis-element for SCD promoter activity [32].
• Reduction in the occurrence of SCD will require community (mobile resuscitation units), public health (control of primary risk factors), and physician-initiated (anti-arrhythmic therapy) measures [33].

References