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Lysophosphatidic acid (LPA) as a modulator of plasma membrane Ca2+-ATPase from basolateral membranes of kidney proximal tubules

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Abstract

Lysophosphatidic acid (LPA) acts through the activation of G protein-coupled receptors, in a Ca2+-dependent manner. We show the effects of LPA on the plasma membrane Ca2+-ATPase (PMCA) from kidney proximal tubule cells. The Ca2+-ATPase activity was inhibited by nanomolar concentrations of LPA, with maximal inhibition (~50%) obtained with 20 nM LPA. This inhibitory action on PMCA activity was blocked by Ki16425, an antagonist for LPA receptors, indicating that this lipid acts via LPA1 and/or LPA3 receptor. This effect is PKC-dependent, since it is abolished by calphostin C and U73122, PKC, and PLC inhibitors, respectively. Furthermore, the addition of 10−8 M PMA, a well-known PKC activator, mimicked PMCA modulation by LPA. We also demonstrated that the PKC activation leads to an increase in PMCA phosphorylation. These results indicate that LPA triggers LPA1 and/or LPA3 receptors at the BLM, inducing PKC-dependent phosphorylation with further inhibition of PMCA. Thus, LPA is part of the regulatory lipid network present at the BLM and plays an important role in the regulation of intracellular Ca2+ concentration that may result in significant physiological alterations in other Ca2+-dependent events ascribed to the renal tissue.

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Acknowledgements

The authors would like to thank Mr. Celso Pereira for helpful technical services.

Funding

This work was supported by grants from CNPq, CAPES/PROBITEC, and Fundação Carlos Chagas Filho de Amparo a Pesquisa do Estado do Rio de Janeiro (FAPERJ).

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Author notes

  1. Julliana F. Sant’Anna and Vanessa S. Baldez contributed equally to this work.

Authors and Affiliations

  1. Laboratório de Biomembranas, Instituto de Biofísica Carlos Chagas Filho, CCS, Universidade Federal do Rio de Janeiro, 21949-902, Ilha do Fundão, Rio de Janeiro, Brasil

    Julliana F. Sant’Anna, Vanessa S. Baldez, Natalie A. Razuck-Garrão, Thiago Lemos & Marcelo Einicker-Lamas

  2. Laboratório de Inflamação, Instituto de Biofísica Carlos Chagas Filho, CCS, Universidade Federal do Rio de Janeiro, 21949-902, Ilha do Fundão, Rio de Janeiro, Brasil

    Bruno L. Diaz

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  1. Julliana F. Sant’Anna
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  2. Vanessa S. Baldez
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  3. Natalie A. Razuck-Garrão
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  4. Thiago Lemos
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Contributions

Statement: The authors declare that all data were generated in-house and that no paper mill was used.

JFS: Experimental design, performed experiments, data interpretation, discussion of the results, and written and revision of the manuscript

VSB: Experimental design, performed experiments, data interpretation, and discussion of the results

NAR-G: Experimental design, performed experiments, data interpretation, discussion of the results

TL: Experimental design, performed experiments, data interpretation, and discussion of the results

BLD: Experimental design, performed experiments, data interpretation, discussion of the results, and written and revision of the manuscript

ME-L: Experimental design, performed experiments, data interpretation, discussion of the results, written and revision of the manuscript, and financial support

Corresponding authors

Correspondence to Bruno L. Diaz or Marcelo Einicker-Lamas.

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Research involving human participants and/or animals

Pig kidneys were purchased from Frigorífico Novo Meriti (São João de Meriti, RJ, Brazil), in accordance to the Federal Law No. 5760, as explained in the “Material and methods” section.

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Highlights

• Lysophosphatidic acid (LPA) can be a modulator of Ca2+-ATPase.

• PKC-dependent control of intracellular Ca2+ in renal cells.

• LPA included in the bioactive lipids network controlling renal function.

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Sant’Anna, J.F., Baldez, V.S., Razuck-Garrão, N.A. et al. Lysophosphatidic acid (LPA) as a modulator of plasma membrane Ca2+-ATPase from basolateral membranes of kidney proximal tubules. J Physiol Biochem 77, 321–329 (2021). https://doi.org/10.1007/s13105-021-00800-5

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