If the Gapdh Gene is Continuously Expressed

Abstract—

The most important property of a living organism is the maintenance of optimal acid–base balance and the ionic composition of the internal environment. The kidneys are one of the main pH-regulating organs in the body. Receptor tyrosine kinase IRR (an insulin receptor-related receptor) is an alkaline pH-sensor. In mice (Mus Musculus) with a knockout of the insrr gene encoding the IRR receptor, bicarbonate secretion is impaired under the conditions of alkaline loading, which indicates the role of the receptor tyrosine kinase IRR in the regulation of acid–base balance in the body. In order to search for proteins functionally associated with the receptor tyrosine kinase IRR, we performed a large-scale sequencing of the mouse kidney transcriptome of wild type and insrr knockout mice kept under normal conditions and under alkaline conditions. As a result, we found a decrease in the gapdh gene expression in the kidneys of insrr knockout mice compared to wild type mice. RNA sequencing data were confirmed by TaqMan real-time PCR and Western blotting. Using the TaqMan real-time PCR method, we revealed a decrease in the level of gapdh expression not only in the kidneys, but also in the liver and brain of insrr knockout mice. Thus, the changes in the gapdh gene expression in the kidneys of insrr knockout mice may indicate a functional relationship between genes and a possible role of GAPDH in previously undescribed molecular mechanisms of regulation of acid–base balance in the body.

REFERENCES

  1. Clayton-smith, M., Renal physiology and acid-base balance, Anaesthesiol. Intensive Care Med., 2021, vol. 22, pp. 415–421.

    Article  Google Scholar

  2. Deyev, I.E., Popova, N.V., Serova, O.V., et al., Alkaline pH induces IRR-mediated phosphorylation of IRS-1 and actin cytoskeleton remodeling in a pancreatic beta cell line, Biochimie, 2017, vol. 138, pp. 62–69.

    Article  CAS  Google Scholar

  3. Serova, O.V., Gantsova, E.A., Deyev, I.E., et al., The Value of pH sensors in maintaining homeostasis of the nervous system, Russ. J. Bioorg. Chem., 2020, vol. 46, pp. 369–384.

    Article  Google Scholar

  4. Meijles, D.N., Fuller, S.J., Cull, J.J., et al., The insulin receptor family and protein kinase B (Akt) are activated in the heart by alkaline pH and α1-adrenergic receptors, Biochem. J., 2021, vol. 478, no. 11, pp. 2059–2079.

    Article  CAS  Google Scholar

  5. Eladari, D., Leviel, F., Pezy, F., et al., Rat proximal NHE3 adapts to chronic acid-base disorders but not to chronic changes in dietary NaCl intake, Am. J. Physiol.: Renal, Fluid Electrolyte Physiol., 2002, vol. 282, pp. 835–843.

    Article  Google Scholar

  6. Sabolić, I., Brown, D., Gluck, S.L., et al., Regulation of AE1 anion exchanger and H+-ATPase in rat cortex by acute metabolic acidosis and alkalosis, Kidney Int., 1997, vol. 51, pp. 125–137.

    Article  Google Scholar

  7. Wagner, C.A., Finberg, K.E., Stehberger, P.A., et al., Regulation of the expression of the Cl–/anion exchanger pendrin in mouse kidney by acid-base status, Kidney Int., 2002, vol. 62, no. 6, pp. 2109–2117.

    Article  CAS  Google Scholar

  8. Gantsova, E.A., Deev, I. E., Petrenko, A.G., et al., Analysis of development of insrr knockout mouse primplantation embryos, Ontogenez, 2022, vol. 53, pp. 196–202.

    Google Scholar

  9. Hildyard, J.C.W., Finch, A.M., and Wells, D.J., Identification of qPCR reference genes suitable for normalizing gene expression in the mdx mouse model of Duchenne muscular dystrophy, PLoS One, 2019, vol. 14, no. 1, art. ID e0211384.

    Article  CAS  Google Scholar

  10. Serova, O.V., Gantsova, E.A., and Deev, I.E., Tissue-specific expression of neurexin-1α isoforms in rat organs, Bioorg. Khim., 2022, vol. 48, pp. 217–222.

    Google Scholar

  11. Wei, K. and Ma, L., Concept development of housekeeping genes in the high-throughput sequencing era, Yi Chuan = Hered., 2017, vol. 39, no. 2, pp. 127–134.

  12. Barber, R.D., Harmer, D.W., Coleman, R.A., et al., GAPDH as a housekeeping gene: analysis of GAPDH mRNA expression in a panel of 72 human tissues, Physiol. Genomics, 2005, vol. 21, pp. 389–395.

    Article  CAS  Google Scholar

  13. Mozdziak, P.E., Dibner, J.J., and McCoy, D.W., Glyceraldehyde-3-phosphate dehydrogenase expression varies with age and nutrition status, Nutrition, 2003, vol. 19, no. 5, pp. 438–440.

    Article  CAS  Google Scholar

  14. Seidler, N.W., Basic biology of GAPDH, Adv. Exp. Med. Biol., 2013, vol. 985, pp. 1–36.

    Article  Google Scholar

  15. Singh, N. and Bhalla, N., Moonlighting Proteins, Annu. Rev. Genet., 2020, vol. 54, pp. 265–285.

    Article  CAS  Google Scholar

  16. Su, Y., Blake-Palmer, K.G., Fry, A.C., et al., Glyceraldehyde 3-phosphate dehydrogenase is required for band 3 (anion exchanger 1) membrane residency in the mammalian kidney, Am. J. Physiol. Renal Physiol., 2011, vol. 300, pp. F157–F166.

    Article  CAS  Google Scholar

  17. Baba, T., Kobayashi, H., Kawasaki, H., et al., Glyceraldehyde-3-phosphate dehydrogenase interacts with phosphorylated Akt resulting from increased blood glucose in rat cardiac muscle, FEBS Lett., 2010, vol. 584, no. 13, pp. 2796–2800.

    Article  CAS  Google Scholar

  18. Deev, I.E., Rzhevski, D.I., Berchatova, A.A., et al., Decompensation metabolic alkalosis in mice with knockout of the insrr gene, Acta Nat., 2011, vol. 4, pp. 119–122.

    Google Scholar

  19. Zubkov, E.A., Morozova, A.Y., Chachina, N.A., et al., Behavioral Characteristics of mice with knockout of the IRR alkali sensor gene, Neurosci. Behav. Physiol., 2018, vol. 48, pp. 483–487.

    Article  CAS  Google Scholar

  20. Deyev, I.E., Sohet, F., Vassilenko, K.P., et al., Insulin receptor-related receptor as an extracellular alkali sensor, Cell Metab., 2011, vol. 13, no. 6, pp. 679–689.

    Article  CAS  Google Scholar

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Funding

The work was supported by the Russian Foundation for Basic Research, grants nos. 19-34-90177 and 20-04-00880.

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Correspondence to E. A. Gantsova.

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The authors declare that they have no conflict of interest.

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Translated by E. V. Makeeva

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Gantsova, E.A., Gavrilenkova, A.A., Serova, O.V. et al. Changes in the Expression of the gapdh Gene in the Organs of insrr Knockout Mice. Dokl Biol Sci 505, 113–118 (2022). https://doi.org/10.1134/S0012496622040056

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  • DOI : https://doi.org/10.1134/S0012496622040056

Keywords:

  • gapdh
  • IRR
  • receptor tyrosine kinases
  • glyceraldehyde-3-phosphate dehydrogenase

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