High parathyroid hormone concentration in tenofovir-treated patients are due to inhibition of calcium-sensing receptor activity

A Mingione, K Maruca, F Chiappori, F Pivari, C Brasacchio, Tiziana Quirino, I Merelli, Laura Soldati, Paolo Bonfanti, S Mora

Research output: Contribution to journalArticle

Abstract

Bone health impairment is a common finding in HIV-infected patients on antiretroviral treatment. High serum parathyroid hormone (PTH) concentration in patients on antiretroviral treatment containing tenofovir disoproxil fumarate (TDF) has been reported. Hyperparathyroidism was not always sustained by a reduction in vitamin D concentration. We thus hypothesized a direct inhibitory effect of TDF on the Calcium-sensing receptor (CaSR), leading to hyperparathyroidism. Human embryonic kidney cells were transfected with CASR wild-type gene or mutated in different sites (N124K, T1051G, C788T, T888M). Cells were grown in standard conditions and the activity of CaSR was assessed after stimulation with CaCl2 with and without TDF (100 nM-1 μM). We evaluated by western blot phospho-p44/42 ERK expression levels as a marker of CaSR activity. In silico structure models were obtained for wild-type and N124K mutant. Molecular docking with TDF was also evaluated. The stimulation by CaCl2 and TDF 100 nM led to a decrease of 55% of CaSR activity (P 
Original languageEnglish
Pages (from-to)969-974
Number of pages6
JournalBiomedicine and Pharmacotherapy
Volume97
Issue number1
DOIs
Publication statusPublished - 2018

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    Mingione, A., Maruca, K., Chiappori, F., Pivari, F., Brasacchio, C., Quirino, T., Merelli, I., Soldati, L., Bonfanti, P., & Mora, S. (2018). High parathyroid hormone concentration in tenofovir-treated patients are due to inhibition of calcium-sensing receptor activity. Biomedicine and Pharmacotherapy, 97(1), 969-974. https://doi.org/10.1016/j.biopha.2017.11.037