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Effects of genetic polymorphisms on the sulfation of doxorubicin by human SULT1C4 allozymes.
Gohal, Saud A; Rasool, Mohammed I; Bairam, Ahsan F; Alatwi, Eid S; Alherz, Fatemah A; Abunnaja, Maryam S; El Daibani, Amal A; Kurogi, Katsuhisa; Liu, Ming-Cheh.
Afiliación
  • Gohal SA; Department of Pharmacology, College of Pharmacy and Pharmaceutical Sciences, University of Toledo Health Science Campus, 3000 Arlington Avenue, Toledo, OH 43614, USA.
  • Rasool MI; Department of Pharmacology, College of Pharmacy and Pharmaceutical Sciences, University of Toledo Health Science Campus, 3000 Arlington Avenue, Toledo, OH 43614, USA.
  • Bairam AF; Department of Pharmacology, College of Pharmacy, University of Karbala, Furaiha Street, Karbala, 56001, Iraq.
  • Alatwi ES; Department of Pharmacology, College of Pharmacy and Pharmaceutical Sciences, University of Toledo Health Science Campus, 3000 Arlington Avenue, Toledo, OH 43614, USA.
  • Alherz FA; Department of Clinical Pharmacy, College of Pharmacy, University of Kufa, Kufa Street, Najaf, 540011, Iraq.
  • Abunnaja MS; Department of Pharmacology, College of Pharmacy and Pharmaceutical Sciences, University of Toledo Health Science Campus, 3000 Arlington Avenue, Toledo, OH 43614, USA.
  • El Daibani AA; Department of Pharmacology, College of Pharmacy and Pharmaceutical Sciences, University of Toledo Health Science Campus, 3000 Arlington Avenue, Toledo, OH 43614, USA.
  • Kurogi K; Department of Pharmaceutical Sciences, College of Pharmacy, Princess Nourah Bint Abdulrahman University, Airport Road, Riyadh, 11564, Saudi Arabia.
  • Liu MC; Department of Pharmacology, College of Pharmacy and Pharmaceutical Sciences, University of Toledo Health Science Campus, 3000 Arlington Avenue, Toledo, OH 43614, USA.
J Biochem ; 170(3): 419-426, 2021 Oct 12.
Article en En | MEDLINE | ID: mdl-33950190
ABSTRACT
Doxorubicin is a chemotherapeutic drug widely utilized in cancer treatment. An enzyme critical to doxorubicin metabolism is the cytosolic sulfotransferase (SULT) SULT1C4. This study investigated the functional impact of SULT1C4 single nucleotide polymorphisms (SNPs) on the sulfation of doxorubicin by SULT1C4 allozymes. A comprehensive database search was performed to identify various SULT1C4 SNPs. Ten nonsynonymous SULT1C4 SNPs were selected, and the corresponding cDNAs, packaged in pGEX-2TK expression vector, were generated via site-directed mutagenesis. Respective SULT1C4 allozymes were bacterially expressed and purified by affinity chromatography. Purified SULT1C4 allozymes, in comparison with the wild-type enzyme, were analysed for sulphating activities towards doxorubicin and 4-nitrophenol, a prototype substrate. Results obtained showed clearly differential doxorubicin-sulphating activity of SULT1C4 allozymes, implying differential metabolism of doxorubicin through sulfation in individuals with distinct SULT1C4 genotypes.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Sulfotransferasas / Doxorrubicina / Polimorfismo de Nucleótido Simple Límite: Humans Idioma: En Revista: J Biochem Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Sulfotransferasas / Doxorrubicina / Polimorfismo de Nucleótido Simple Límite: Humans Idioma: En Revista: J Biochem Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos