Literature summary for 6.3.2.2 extracted from

Hosomi, H.; Akai, S.; Minami, K.; Yoshikawa, Y.; Fukami, T.; Nakajima, M.; Yokoi, T.
An in vitro drug-induced hepatotoxicity screening system using CYP3A4-expressing and gamma-glutamylcysteine synthetase knockdown cells (2010), Toxicol. In Vitro, 24, 1032-1038.

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Application

Application	Comment	Organism
pharmacology	three days infection of GCSh-shRNA and CYP3A4 simultaneously with H4IIE cells decreases the intracellular GSH level by 50-60% without affecting the expression level of CYP3A4. Using this cell-based system sensitive to the cytotoxicity of reactive metabolites, drugs known for their hepatotoxicity are evaluated. Troglitazone, flutamide, and acetaminophen cause significant decreases of cell viability in CYP3A4/GCSh-shRNA group compared to the other groups such as GFP, CYP3A4, GFP/GCSh-shRNA, indicating that reactive metabolites produced by CYP3A4 and subsequently conjugated by GSH are involved in the cytotoxicity	Rattus norvegicus

Cloned(Commentary)

Cloned (Comment)	Organism
expression in 293 and H4IIE cell lines	Rattus norvegicus

Organism

Organism	UniProt	Comment	Textmining
Rattus norvegicus	P19468	catalytic subunit	-

General Information

General Information	Comment	Organism
physiological function	knockdown of gamma-glutamylcysteine synthetase heavy chain subunit by an adenovirus vector with short hairpin RNA against GCSh. Three days infection of GCSh-shRNA and CYP3A4 simultaneously with H4IIE cells decreases the intracellular GSH level by 50-60% without affecting the expression level of CYP3A4. Using this cell-based system sensitive to the cytotoxicity of reactive metabolites, drugs known for their hepatotoxicity are evaluated. Troglitazone, flutamide, and acetaminophen cause significant decreases of cell viability in CYP3A4/GCSh-shRNA group compared to the other groups such as GFP, CYP3A4, GFP/GCSh-shRNA, indicating that reactive metabolites produced by CYP3A4 and subsequently conjugated by GSH are involved in the cytotoxicity	Rattus norvegicus

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Release 2023.1 (January 2023)