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Murine Renal Cell Isolation: A Technique to Isolate and Generate Primary Culture of Renal Tubular Epithelial Cells
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5-ALA/SFC enhances HO-1 expression through the MAPK/Nrf2 antioxidant pathway and attenuates murine tubular epithelial

Chi Liu1, Masayuki Fujino1,2, Shuoji Zhu3

  • 1Division of Transplantation Immunology, National Research Institute for Child Health and Development, Tokyo, Japan.

FEBS Open Bio
|September 9, 2019
PubMed

Insights

5-aminolevulinic acid and iron (5-ALA/SFC) protect kidney cells from immunosuppressant Cyclosporin A (CsA) toxicity. This compound reduces oxidative stress and apoptosis, offering potential therapeutic benefits against CsA-induced nephrotoxicity.

Area of Science:

  • Nephrology
  • Biochemistry
  • Cell Biology

Background:

  • Cyclosporin A (CsA) is a vital immunosuppressant with limited use due to nephrotoxicity.
  • Oxidative stress and apoptosis are key mechanisms in CsA-induced kidney injury.

Purpose of the Study:

  • To investigate the protective effects of 5-aminolevulinic acid and iron (5-ALA/SFC) against CsA-induced nephrotoxicity.
  • To elucidate the molecular mechanisms underlying the protective action of 5-ALA/SFC.

Main Methods:

  • Utilized murine proximal tubular epithelial cells (mProx24) exposed to CsA.
  • Assessed apoptosis, reactive oxygen species (ROS) production, and key protein expressions (HO-1, Nrf2, p38, Erk-1/2).

Main Results:

  • 5-ALA/SFC significantly inhibited CsA-induced apoptosis in mProx24 cells.
  • 5-ALA/SFC treatment increased heme oxygenase (HO)-1, nuclear factor E2-related factor 2 (Nrf2), and p38/Erk-1/2 phosphorylation.
  • 5-ALA/SFC suppressed ROS production; HO-1 inhibition abolished the protective effects.

Conclusions:

  • 5-ALA/SFC demonstrates significant anti-nephrotoxic and anti-apoptotic effects against CsA.
  • The protective mechanism involves the upregulation of HO-1 and modulation of Nrf2 and MAPK signaling pathways.
  • 5-ALA/SFC holds potential for therapeutic development to mitigate CsA-induced kidney injury.
Keywords:
5-aminolevulinic acidCyclosporine Aapoptosisheme oxygenase-1oxidative stress

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