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The Role of Fecal Microflora in Colon Carcinogenesis
Published in Herman Autrup, Gary M. Williams, Experimental Colon Carcinogenesis, 2019
Cholesterol may be metabolized to coprostanol and coprostanone (Figure 2) by a range of fecal bacteria including bacteroides, bifidobacteria, and Clostridia, although the reproducibility of this process clearly depends upon the incubation conditions.35,36 In a separate study, incubation of cholesterol with E. coli in the presence of DNA led to the formation of DNA-bound products.37 This observation is particularly important as the somatic theory of chemical carcinogenesis correlates the induction of cancer with the modification of cellular DNA as the initial lesion. The major breakdown products from cholesterol are not in themselves carcinogens, but may be further degraded to active species via side chain loss. In model systems, such as incubation of sitosterol with mycobacterium fortuitum strains38 or Cortisol with human fecal suspensions,39 there was a loss of side-chain substituents leading to the formation of unsaturated androstane derivatives. Identification of the DNA-bound products isolated from the E. coli incubations would yield valuable information on the possible role of choiesterol metabolites in carcinogenesis. Reddy et al.40 have demonstrated the presence of 3β, 5α, 6β,trihydroxy cholestane, presumably derived from cholesterol-5α, 6α-epoxide in the feces of cancer patients, although there is no direct evidence that this substrate is microbially derived.
Solanine (Nightshade Glycoalkaloids)
Published in Dongyou Liu, Handbook of Foodborne Diseases, 2018
Filomena Lelario, Laura Scrano, Sabino Aurelio Bufo, Maryam Bader, Donia Karaman, Ameen Thawabteh, Rafik Karaman
Solanum alkaloids are steroidal alkamines that all have in common the C27 steroidal skeleton of cholestane. These alkaloids are classified into five groups based on their structure: solanidanes; spirosolanes; 22,26-epiminocholestanes; epiminocyclohemiketals; and 3-aminospirostanes [27]. The structures of these alkamines are shown in Figure 105.1.
The Effects of Experimental Diabetes on the Cytochrome P450 System and Other Metabolic Pathways
Published in John H. McNeill, Experimental Models of Diabetes, 2018
Costas Ioannides, Peter R. Flatt, Christopher R. Barnett
The expression of the cytochrome P450 proteins, whose primary function is the metabolism of endogenous substrates, in IDDM has received very little attention. Cholesterol 7α-hydroxylase (CYP7), the rate-limiting step in the catabolism of cholesterol to bile acids was higher in the liver of rats made diabetic by streptozotocin treatment; the effect was successfully antagonized by insulin.86 Similarly, the 12α-hydroxylation of 5β-cholestane- 3α,7α-diol, a pathway involved in bile acid biosynthesis, was elevated in IDDM rats.87 Pathways of hepatic steroid metabolism are also differentially modulated by the induction of IDDM in rats using streptozotocin.88
Current advancements in therapy for Niemann-Pick disease: progress and pitfalls
Published in Expert Opinion on Pharmacotherapy, 2023
Tatiana Bremova-Ertl, Susanne Schneider
Niemann-Pick disease type C (NPC) is an autosomal recessive inherited neurovisceral lysosomal storage disease (LSD) caused by mutations in the NPC1 or NPC2 gene. NPC is characterized by impaired intracellular transport of endocytosed unesterified cholesterol, sphingomyelin, glycosphingolipids and sphingosine with their sequestration in lysosomes and late endosomes [1,2]. The accumulated cholesterol undergoes non-enzymatic oxidation, leading to a formation of oxysterols, including cholestane-3β,5α,6β-triol (C-triol) and 7-ketocholesterol (7-KC) [3,4]. They are used as blood-based biomarkers of NPC, together with certain plasma bile acids [5] (e.g. 3β,5α,6β-trihydroxycholanic acid) and certain lysosphingolipids [6] (e.g.lyso-SM-509), supplanting filipin staining as first-line diagnostics.
Interaction of Alpha-Crystallin with Phospholipid Membranes
Published in Current Eye Research, 2021
Laxman Mainali, William J. O’Brien, Raju Timsina
One-palmitoy-2-oleoyl-sn-glycero-3-phosphatidylcholine (POPC) was purchased from Avanti Polar Lipids, Inc. (Alabaster, AL, USA). Cholesterol analog cholestane spin label (CSL) was obtained from Molecular Probes (Eugene, OR, USA). We have chosen CSL spin-label in the proposed research because the nitroxide moiety of CSL is close to the membrane surface and it was reported earlier by another research group32 that the headgroup region of the membrane becomes less mobile with binding of α-crystallin. Bovine eye lens α-crystallin and other chemicals (of at least reagent grade) were purchased from Sigma-Aldrich (St. Louis, MO, USA). The α-crystallin (C4163) purchased from Sigma-Aldrich was used without any further purification. The molecular weight of α-crystallin was estimated to be 20.35 kDa based on the information provided by Sigma-Aldrich via phone (i.e., αA = 19.8 kDa, αB = 22 kDa, αA:αB = 3:1). As estimated by other research groups,38,39 the isolation of α-crystallin from native bovine eye lens consists of about 6% other lens protein. The possibility of these other proteins binding to the membrane cannot be ignored; however, with α-crystallin being the most abundant protein, we suggest that the change we observe in the lipid organization and dynamics sensed by CSL in the membrane is most likely due to α-crystallin. The possible effect of impurities on Ka and membrane properties can be eliminated by using recombinant pure α-crystallin. We plan to use recombinant pure α-crystallin in our future studies, as used by other research groups.33,40
Lipidomic analysis of cancer cells cultivated at acidic pH reveals phospholipid fatty acids remodelling associated with transcriptional reprogramming
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2020
Lorena Urbanelli, Sandra Buratta, Mariantonia Logozzi, Nico Mitro, Krizia Sagini, Rossella Di Raimo, Donatella Caruso, Stefano Fais, Carla Emiliani
Total cholesterol quantitative analysis was performed as previously described41. Briefly, an aliquot of fraction B was first derivatized with a mixture of bis-trimethylsilyltrifluoroacetamide (BSTFA): pyridine (4:1 v/v) for 30 min at 60 °C, and then injected into a gas chromatograph-mass spectrometer (GC-MS, Varian Saturn 2100). The MS was operated in the electron impact (EI) ionisation mode. GC-MS analysis was performed as follows: 1 μl sample was injected in splitless mode (inlet was kept at 270 °C with the helium flow at 1.0 ml/min) at the initial 180 °C. The oven was first kept at 180 °C for 1 min, ramped at 50 °C/min to 240 °C, then at 5 °C/min to 300 °C for 6 min. The ions used for the quantification of cholesterol were at m/z 368 for cholesterol and m/z 357 for 5α-cholestane, the IS. The selection of ions for selective ion monitoring (SIM) analysis was based on mass spectra of pure standards and the quantification was based on calibration curves freshly prepared using a fixed concentration of the IS, and different concentrations of cholesterol, in a range from 0 to 10 μg/μl. Quantitative data were normalised on the protein content of cells.