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Inverse association between microRNA-124a and ABCC4 in HepG2 cells treated with antiretroviral drugs.
Nagiah, Savania; Phulukdaree, Alisa; Chuturgoon, Anil.
Afiliación
  • Nagiah S; a Discipline of Medical Biochemistry, School of Laboratory Medicine and Medical Science, College of Health Science, University of KwaZulu Natal , Durban , South Africa.
  • Phulukdaree A; a Discipline of Medical Biochemistry, School of Laboratory Medicine and Medical Science, College of Health Science, University of KwaZulu Natal , Durban , South Africa.
  • Chuturgoon A; a Discipline of Medical Biochemistry, School of Laboratory Medicine and Medical Science, College of Health Science, University of KwaZulu Natal , Durban , South Africa.
Xenobiotica ; 46(9): 825-30, 2016 Sep.
Article en En | MEDLINE | ID: mdl-26643107
The ATP-binding cassette (ABC) super-family of drug transporters regulates efflux of xenobiotic compounds. The subfamily, multi-drug resistance proteins (MRPs) transports cyclic nucleotides and xenobiotics. Epigenetic modulation of drug transporters is scarcely described. The regulatory role of microRNA (miR)-124a on drug transporter gene ABCC4 was only recently reported. Our study investigated the differential regulation of miR-124a by nucleoside reverse transcriptase inhibitors (NRTIs): Zidovudine (AZT), Stavudine (d4T) and Tenofovir (TFV); at 24 h and 120 h treatments in HepG2 cells. ABCC4 mRNA (qPCR) and ABCC4 protein (western blot) were quantified. Cytotoxicity was evaluated by lactate dehydrogenase (LDH) levels. All NRTIs elevated miR-124a levels at 24 h, with a concomitant decline in ABCC4 mRNA levels (p<0.05). At 120 h, d4T and TFV elevated miR-124a and depleted ABCC4 mRNA levels (p<0.0001), while the inverse was observed with AZT (p<0.005). ABCC4 protein was increased by d4T and TFV at 24h. A significant reduction in protein levels was observed at 120 h in all three treatments (p<0.005). The disjoint in mRNA and protein levels is likely due to ABCC4 being a membrane bound protein. Following prolonged exposure, membrane integrity was compromised as evidenced by increased LDH leakage (p<0.005). We conclude antiretroviral drugs have varying effects on miR-124a and ABCC4.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Transportadoras de Casetes de Unión a ATP / MicroARNs / Antirretrovirales Tipo de estudio: Risk_factors_studies Límite: Humans Idioma: En Revista: Xenobiotica Año: 2016 Tipo del documento: Article País de afiliación: Sudáfrica

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Transportadoras de Casetes de Unión a ATP / MicroARNs / Antirretrovirales Tipo de estudio: Risk_factors_studies Límite: Humans Idioma: En Revista: Xenobiotica Año: 2016 Tipo del documento: Article País de afiliación: Sudáfrica