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Kinetic mechanisms by which nickel alters the calcium (Ca2+) transport in intact rat liver

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Abstract

In the present work, the multiple-indicator dilution (MID) technique was used to investigate the kinetic mechanisms by which nickel (Ni2+) affects the calcium (Ca2+) transport in intact rat liver. 45Ca2+ and extra- and intracellular space indicators were injected in livers perfused with 1 mM Ni2+, and the outflow profiles were analyzed by a mathematical model. For comparative purposes, the effects of norepinephrine were measured. The influence of Ni2+ on the cytosolic Ca2+ concentration ([Ca2+]c) in human hepatoma Huh7 cells and on liver glycogen catabolism, a biological response sensitive to cellular Ca2+, was also evaluated. The estimated transfer coefficients of 45Ca2+ transport indicated two mechanisms by which Ni2+ increases the [Ca2+]c in liver under steady-state conditions: (1) an increase in the net efflux of Ca2+ from intracellular Ca2+ stores due to a stimulus of Ca2+ efflux to the cytosolic space along with a diminution of Ca2+ re-entry into the cellular Ca2+ stores; (2) a decrease in Ca2+ efflux from the cytosolic space to vascular space, minimizing Ca2+ loss. Glycogen catabolism activated by Ni2+ was transient contrasting with the sustained activation induced by norepinephrine. Ni2+ caused a partial reduction in the norepinephrine-induced stimulation in the [Ca2+]c in Huh7 cells. Our data revealed that the kinetic parameters of Ca2+ transport modified by Ni2+ in intact liver are similar to those modified by norepinephrine in its first minutes of action, but the membrane receptors or Ca2+ transporters affected by Ni2+ seem to be distinct from those known to be modulated by norepinephrine.

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Funding

This work was supported by grants from the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq—308980/2017–4) and Coordenação de Aperfeiçoamento de Pessoal do Ensino Superior (CAPES/NUFFIC n°14/10). Karina Sayuri Utsunomiya holds fellowship from the Conselho Nacional de Desenvolvimento Científico e Tecnológico.

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Authors and Affiliations

  1. Laboratory of Biological Oxidations, Department of Biochemistry, State University of Maringá, Avenida Colombo 5790, Maringá, Paraná, 87020900, Brazil

    Karina Sayuri Utsunomiya, Lucas Jonatas da Silva, Juliana Iwamoto, Rodrigo Polimeni Constantin, Eduardo Hideo Gilglioni, Jorgete Constantin, Adelar Bracht & Emy Luiza Ishii-Iwamoto

  2. Tytgat Institute for Liver and Intestinal Research, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

    Ronald Petrus Johannes Oude Elferink

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  1. Karina Sayuri Utsunomiya
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  2. Lucas Jonatas da Silva
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Contributions

KSU: Investigation, validation, formal analysis, writing—original draft. LJdS: Investigation, validation. JI: Investigation, validation. RPC: Visualization, writing—review and editing. EHG: Visualization. JC: Writing—review and editing. AB: Methodology, software. RPJOE: Supervision, writing—review and editing. ELI-I: Supervision, project administration, funding acquisition, writing—original draft, review and editing.

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Correspondence to Emy Luiza Ishii-Iwamoto.

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All experiments were conducted in strict adherence with the guidelines of the National Council for the Control of Animal Experimentation CONCEA (law no. 11.794 October 8, 2008) and The Ethics Committee on Animal Use (CEUA), of the State University of Maringa (Resolution n° 004/20160CEP), which follows the internationally accepted recommendations for the care and use of animals.

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Utsunomiya, K.S., da Silva, L.J., Iwamoto, J. et al. Kinetic mechanisms by which nickel alters the calcium (Ca2+) transport in intact rat liver. J Biol Inorg Chem 26, 641–658 (2021). https://doi.org/10.1007/s00775-021-01883-7

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