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Insects Sep 2021Arthropods, including insects, convert sterols into cholesterol due to the inability to synthesise cholesterol de novo. 24-dehydrocholesterol reductase (DHCR24) plays an...
Arthropods, including insects, convert sterols into cholesterol due to the inability to synthesise cholesterol de novo. 24-dehydrocholesterol reductase (DHCR24) plays an important role in the conversion. Not only involving the cholesterol biosynthesis in vertebrates, DHCR24 is required for the conversion of desmosterol into cholesterol in phytophagous insects. The current study extensively examined DHCR24 in omnivorous insects, which feed on both plants and animals, using as the experimental model. We identified cDNAs encoding two homologues of DHCR24 from , which were designated as GbDHCR24-1 and GbDHCR24-2. Both homologues contained the flavin adenine dinucleotide binding domain, which is a feature of DHCR24. Quantitative polymerase chain reaction revealed that among tissues of adult crickets, fat body and anterior midgut expressed high levels of GbDHCR24s. Both fat body and anterior midgut demonstrated DHCR24 activities in which one of the functions is the conversion of desmosterol into cholesterol in vitro. Knockdown of GbDHCR24-1 significantly reduced the conversion activity in the anterior midgut while knockdown of the GbDHCR24-2 did not. Additionally, the accumulation of desmosterol was detected in a feeding experiment with a specific DHCR24 inhibitor, azacosterol. We finally concluded that GbDHCR24-1 is the major enzyme that facilitates the desmosterol-to-cholesterol-conversion in crickets.
PubMed: 34564222
DOI: 10.3390/insects12090782 -
Critical Reviews in Toxicology Mar 1981
Comparative Study Review
Topics: Animals; Azacosterol; Carboxylic Acids; Chlorides; Clofibrate; Desmosterol; Humans; Iodides; Membrane Potentials; Muscles; Myotonia; Rats
PubMed: 7026172
DOI: 10.3109/10408448109089901 -
Archives of Dermatology Nov 1987Ichthyosis and other disorders of cornification may occur as side effects of treatment with several hypocholesterolemic agents. Recent progress in understanding of the...
Ichthyosis and other disorders of cornification may occur as side effects of treatment with several hypocholesterolemic agents. Recent progress in understanding of the functional role of lipids in stratum corneum provides a new pathophysiologic basis for these earlier clinical observations. In stratum corneum, lipids are segregated within intercellular membranes, where they appear to regulate permeability barrier function and desquamation. Cholesterol is an important constituent of these membranes and may be essential to both of these functions. Perturbation of barrier function induces cholesterologenesis locally within the epidermis. Polar sterol metabolites, such as cholesterol sulfate, may also regulate epidermal sterologenesis under normal or pathologic circumstances. Cholesterol homeostasis may also modulate desquamation. For example, hairless mice fed azacosterol hydrochloride (20,25-diazacholesterol) develop a generalized scaling disorder without loss of barrier function. In these mice, total stratum corneum sterol content is markedly decreased, and topical or systemic repletion with cholesterol can correct the scaling abnormalities.
Topics: Animals; Anticholesteremic Agents; Cholesterol; Cholesterol Esters; Epidermis; Homeostasis; Humans; Ichthyosis; Lipid Metabolism; Mice; Mice, Hairless; Skin; Sterols
PubMed: 3674913
DOI: No ID Found -
Muscle & Nerve 1980
Topics: 2,4-Dichlorophenoxyacetic Acid; Animals; Anura; Azacosterol; Disease Models, Animal; Muscle Denervation; Myotonia
PubMed: 7421880
DOI: No ID Found -
Journal of Neurochemistry Apr 1984In this report, we examine the requirement of cholesterol biosynthesis and its axonal transport for goldfish optic nerve regeneration. Cholesterol, labeled by...
In this report, we examine the requirement of cholesterol biosynthesis and its axonal transport for goldfish optic nerve regeneration. Cholesterol, labeled by intraocular injection of [3H]mevalonolactone, exhibited a delayed appearance in the optic tectum. Squalene and other minor components were labeled but not transported. Following optic nerve crush, the amount of labeled cholesterol transport was elevated, while retinal labeling was not altered relative to control fish. A requirement for cholesterol biosynthesis is inferred from the inhibition of neurite outgrowth in retinal explants caused by the cholesterol synthesis inhibitor, 20,25-diazacholesterol. The inhibition of growth could be overcome by addition of mevalonolactone, but not cholesterol, to the medium. Intraperitoneal administration of 200 nmol of diazacholesterol resulted in 92-98% inhibition of retinal cholesterol synthesis and accumulation of labeled desmosterol and other lipids in fish retina and brain which persisted for 2 weeks. Diazacholesterol-treated fish showed no reduction in the amount of lipid-soluble radioactivity transported following intraocular injection of [3H]mevalonolactone, but there were alterations in the chromatographic pattern of the transported labeled lipids. In contrast to its effects on neurite outgrowth in vitro, diazacholesterol did not inhibit optic nerve regeneration in vivo, as measured both by arrival of labeled rapidly transported protein at the tectum and by time required for the return of visual function.
Topics: Animals; Axons; Azacosterol; Cholesterol; Desmosterol; Goldfish; Mevalonic Acid; Nerve Regeneration; Optic Nerve; Retina
PubMed: 6699648
DOI: 10.1111/j.1471-4159.1984.tb12701.x -
Neurology Feb 1987We report the occurrence of neurologic complications in 23 patients who underwent gastric restriction surgery for the treatment of morbid obesity. Complications occurred...
We report the occurrence of neurologic complications in 23 patients who underwent gastric restriction surgery for the treatment of morbid obesity. Complications occurred 3 to 20 months after surgery. All the patients had had protracted vomiting for the first 3 months after the operation. The following syndromes were found: chronic or subacute symmetric polyneuropathy (12 patients), acute severe polyneuropathy (1 patient), burning feet syndrome (2 patients), meralgia paresthetica (3 patients), myotonic syndrome (1 patient), posterolateral myelopathy (2 patients), and Wernicke-Korsakoff encephalopathy (2 patients). The patients suffering from burning feet syndrome and those with Wernicke-Korsakoff encephalopathy showed a clear improvement after parenteral thiamine treatment. As to the rest of the patients, the occurrence of the complications seems to be linked to nutritional causes, although no such deficiencies were detected.
Topics: Adult; Azacosterol; Female; Humans; Male; Middle Aged; Myotonia; Obesity, Morbid; Peripheral Nervous System Diseases; Postoperative Complications; Stomach; Wernicke Encephalopathy
PubMed: 3027610
DOI: 10.1212/wnl.37.2.196 -
Effects of diazacholesterol dihydrochloride (SC-12937), an avian antifertility agent, on rat testis.Journal of Andrology 1986The present study was undertaken to evaluate the effectiveness of an avian chemosterilant, 20, 25-diazacholesterol dihydrochloride (SC-12937), on the rat testis. Adult...
The present study was undertaken to evaluate the effectiveness of an avian chemosterilant, 20, 25-diazacholesterol dihydrochloride (SC-12937), on the rat testis. Adult male rats were injected intraperitoneally with 10 mg (Group 1) or 30 mg (Group 2) of SC-12937/kg/d or with vehicle alone (Group 3) for 10 days, and were killed 24 hours after the last injection. A wide range of variation in the appearance of affected seminiferous tubules was observed in the testis of SC-12937-treated rats at both dose levels. This ranged from apparently normal-looking seminiferous tubules to almost completely atrophied tubules with no cells. Affected tubules exhibited intraepithelial vacuoles of varying size, multinucleated giant cells, germ cell exfoliation, and tubular atrophy. The presence of severely damaged and entirely normal seminiferous tubules adjacent to one another in the same section was noteworthy. The changes appeared to be dose-related. A greater number (34.6%) of affected tubules were observed in rats receiving 30 mg of SC-12937 compared with the ones receiving 10 mg of this compound (19.6%). The Sertoli cells also were affected by this drug and exhibited cytoplasmic vacuolation, a marked increase in the accumulation of lipid droplets and myeloid bodies. Necrotic Sertoli cells also were observed in the severely affected tubules. The possible mechanism of antispermatogenic action of SC-12937 in rats has been discussed briefly.
Topics: Animals; Anticholesteremic Agents; Azacosterol; Body Weight; Cholesterol; Contraceptive Agents, Male; Male; Microscopy, Electron; Organ Size; Rats; Seminiferous Tubules; Sertoli Cells; Spermatogenesis; Testis
PubMed: 3771367
DOI: 10.1002/j.1939-4640.1986.tb00930.x -
Bioscience Reports Feb 1984Previous spin-label and electromyographic experiments with rats fed 20,25-diazacholesterol, an inhibitor of the biosynthetic conversion of desmosterol to cholesterol,...
Membrane fluidity and myotonia: effects of cholesterol and desmosterol on erythrocyte membrane fluidity in rats with 20,25-diazacholesterol-induced myotonia and on phospholipid liposomes.
Previous spin-label and electromyographic experiments with rats fed 20,25-diazacholesterol, an inhibitor of the biosynthetic conversion of desmosterol to cholesterol, demonstrated an increased erythrocyte membrane fluidity and myotonia, a prolonged muscle contraction upon stimulation. The current studies with rats showed normal erythrocyte fluidity in animals fed 20,25-diazacholesterol but maintained on a high-cholesterol diet and no myotonia. Studies of model membrane systems composed of phospholipid vesicles containing desmosterol, cholesterol, or both demonstrated that desmosterol increased membrane lipid fluidity relative to cholesterol, suggesting that in 20,25-diazacholesterol-induced myotonia, in which desmosterol accounts for 85% of the plasma sterol, the increased membrane fluidity previously observed in erythrocytes and sarcolemma in this animal model of human congenital myotonia may be due to desmosterol.
Topics: Animals; Azacosterol; Cholesterol, Dietary; Desmosterol; Disease Models, Animal; Erythrocyte Membrane; Liposomes; Male; Membrane Fluidity; Myotonia; Rats; Rats, Inbred Strains
PubMed: 6713083
DOI: 10.1007/BF01120307 -
Poultry Science Feb 2004Contraception may provide a useful nonlethal management tool when it is desirable to reduce populations of birds. We tested the efficacy of 20,25 diazacholesterol, and...
Effectiveness of twenty, twenty-five diazacholesterol, avian gonadotropin-releasing hormone, and chicken riboflavin carrier protein for inhibiting reproduction in Coturnix quail.
Contraception may provide a useful nonlethal management tool when it is desirable to reduce populations of birds. We tested the efficacy of 20,25 diazacholesterol, and immunization with avian gonadotropin-releasing hormone (AGnRH-I) and chicken riboflavin carrier protein (cRCP) as contraceptives and investigated their modes of action in Coturnix quail (Coturnix coturnix japonica). Females that were paired with males treated with 20,25 diazacholesterol produced lower percentages of eggs that were fertile and hatched. Females treated with 20,25 diazacholesterol and paired with control males laid fewer eggs, and lower percentages of their eggs were fertile and hatched. Treatment with 20,25 diazacholesterol reduced testosterone levels in males and progesterone levels in females. Nonesterified cholesterol levels were reduced, whereas desmosterol levels increased in birds treated with 20,25 diazacholesterol. Treatment with AGnRH-I and cRCP immunocontraceptive vaccines did not decrease average egg production and hatchability or hormone levels, but this failure might have been due to the vaccination protocol. If registered, wildlife managers may be able to use 20,25 diazacholesterol when other methods, such as lethal control, are undesirable for reducing damage caused by specific breeding behaviors such as the building of nests.
Topics: Animals; Anticholesteremic Agents; Azacosterol; Carrier Proteins; Cholesterol; Contraceptive Agents; Coturnix; Desmosterol; Female; Fertility; Gonadotropin-Releasing Hormone; Male; Membrane Transport Proteins; Oviposition; Progesterone; Riboflavin; Testosterone; Treatment Outcome
PubMed: 14979575
DOI: 10.1093/ps/83.2.234 -
Bioorganic & Medicinal Chemistry May 2001A number of aza-steroids were synthesized as potent phosphatidylinositol phospholipase C (PI-PLC) inhibitors. The epimeric mixtures 22,25-diazacholesterol (8a) and...
A number of aza-steroids were synthesized as potent phosphatidylinositol phospholipase C (PI-PLC) inhibitors. The epimeric mixtures 22,25-diazacholesterol (8a) and 3beta-hydroxy-22,25-diazacholestane (8b) were among the most active of these inhibitors, with IC(50) values of 7.4 and 7.5 microM, respectively. The 20alpha epimer, 8a2 (IC(50)=0.64 microM), whose stereochemistry at C-20 coincides with that of cholesterol, was found 50 times more potent than the 20beta epimer, 8a1 (IC(50)=32.2 microM). In diaza-estrone derivatives, the 3-methoxy group on the aromatic A-ring of 23 exhibited moderate PI-PLC inhibitory activity (IC(50)=19.7 microM), while compound with a free hydroxyl group (21) was inactive. However, in diaza-pregnane derivatives, epimers with a 3-hydroxyl group (8a, IC(50)=7.4 microM) exhibited more potent PI-PLC inhibitory activity than their counterparts with 3-methoxyl group on the non-aromatic A-ring (26, IC(50)=17.4 microM). We have illustrated in our previous publication that 3-hydroxyl-6-aza steroids are potent PI-PLC inhibitors.(3) However, simultaneous presence of the 6-aza and 22,25-diaza moieties in one molecule as in 13, led to loss of activity. Epimeric mixture 8a showed selective growth inhibition effects in the NCI in vitro tumor cell screen with a mean GI(50) value (MG-MID) of 5.75 microM for 54 tumors.
Topics: Azacosterol; Azasteroids; Cholestanols; Drug Screening Assays, Antitumor; Enzyme Inhibitors; Humans; Inhibitory Concentration 50; Phosphatidylinositol Diacylglycerol-Lyase; Phosphoinositide Phospholipase C; Structure-Activity Relationship; Tumor Cells, Cultured; Type C Phospholipases
PubMed: 11377165
DOI: 10.1016/s0968-0896(00)00302-3