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001-es BibID:	BIBFORM072690
Első szerző:	Korade, Zeljka
Cím:	Vulnerability of DHCR7+/- mutation carriers to aripiprazole and trazodone exposure / Zeljka Korade, Thiago C. Genaro-Mattos, Keri A. Tallman, Wei Liu, Krassimira A. Garbett, Katalin Koczok, Istvan Balogh, Karoly Mirnics, Ned A. Porter
Dátum:	2017
ISSN:	0022-2275
Megjegyzések:	Smith-Lemli-Opitz syndrome is a recessive disorder caused by mutations in 7-dehydrocholesterol reductase (DHCR)7 with a heterozygous (HET) carrier frequency of 1-3%. A defective DHCR7 causes accumulation of 7-dehydrocholesterol (DHC), which is a highly oxidizable and toxic compound. Recent studies suggest that several antipsychotics, including the highly prescribed pharmaceuticals, aripiprazole (ARI) and trazodone (TRZ), increase 7-DHC levels in vitro and in humans. Our investigation was designed to compare the effects of ARI and TRZ on cholesterol (Chol) synthesis in fibroblasts from DHCR7+/- human carriers and controls (CTRs). Six matched pairs of fibroblasts were treated and their sterol profile analyzed by LC-MS. Significantly, upon treatment with ARI and TRZ, the total accumulation of 7-DHC was higher in DHCR7-HET cells than in CTR fibroblasts. The same set of experiments was repeated in the presence of 13C-lanosterol to determine residual Chol synthesis, revealing that ARI and TRZ strongly inhibit de novo Chol biosynthesis. The results suggest that DHCR7 carriers have increased vulnerability to both ARI and TRZ exposure compared with CTRs. Thus, the 1-3% of the population who are DHCR7 carriers may be more likely to sustain deleterious health consequences on exposure to compounds like ARI and TRZ that increase levels of 7-DHC, especially during brain development.
Tárgyszavak:	Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban 7-dehydrocholesterol aripiprazole trazodone fibroblasts carriers antipsychotics
Megjelenés:	Journal Of Lipid Research 58 : 11 (2017), p. 2139-2146. -
További szerzők:	Genaro-Mattos, Thiago C. Tallman, Keri A. Liu, Wei Garbett, Krassimira A. Koczok Katalin (1979-) (labororvos) Balogh István (1972-) (molekuláris biológus, genetikus) Mirnics Károly Porter, Ned A.
Pályázati támogatás:	GINOP-2.3.2-15-2016-00039 GINOP
Internet cím:	DOI Intézményi repozitóriumban (DEA) tárolt változat
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