Rhabdomyolysis-Induced AKI Was Ameliorated in NLRP3 KO Mice via Alleviation of Mitochondrial Lipid Peroxidation in Renal Tubular Cells.

International Journal of Molecular Sciences
Seok Jong SongYang Gyun Kim

Abstract

A recent study showed that early renal tubular injury is ameliorated in Nod-like receptor pyrin domain-containing protein 3 (NLRP3) KO mice with rhabdomyolysis-induced acute kidney injury (RIAKI). However, the precise mechanism has not been determined. Therefore, we investigated the role of NLRP3 in renal tubular cells in RIAKI. Glycerol-mediated RIAKI was induced in NLRP3 KO and wild-type (WT) mice. The mice were euthanized 24 h after glycerol injection, and both kidneys and plasma were collected. HKC-8 cells were treated with ferrous myoglobin to mimic a rhabdomyolytic environment. Glycerol injection led to increase serum creatinine, aspartate aminotransferase (AST), and renal kidney injury molecule-1 (KIM-1) level; renal tubular necrosis; and apoptosis. Renal injury was attenuated in NLRP3 KO mice, while muscle damage and renal neutrophil recruitment did not differ between NLRP3 KO mice and WT mice. Following glycerin injection, increases in cleaved caspase-3, poly (ADP-ribose) polymerase (PARP), and a decrease in the glutathione peroxidase 4 (GPX-4) level were observed in the kidneys of mice with RIAKI, and these changes were alleviated in the kidneys of NLRP3 KO mice. NLRP3 was upregulated, and cell viability was suppresse...Continue Reading

References

Mar 1, 1992·The Journal of Clinical Investigation·R A Zager, C A Foerder
Dec 21, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·H YamagishiY Utsunomiya
Nov 25, 2005·Current Medicinal Chemistry·Brandon J Reeder, Michael T Wilson
Dec 3, 2008·European Journal of Internal Medicine·Yiannis S ChatzizisisGeorge D Giannoglou
Jul 3, 2009·The New England Journal of Medicine·Xavier BoschJosep M Grau
Dec 29, 2009·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Jin Hyun KimDong Jun Park
Oct 22, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Alana A ShigeokaDianne B McKay
Nov 23, 2010·Nature Reviews. Immunology·Grace Y Chen, Gabriel Nuñez
Dec 25, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Wenjie WangDaniel A Muruve
Sep 10, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Hua ShenDaniel Robert Goldstein
Jul 22, 2014·Critical Care : the Official Journal of the Critical Care Forum·Nadezda Petejova, Arnost Martinek
Jul 31, 2014·Kidney International·Khurrum ShahzadBerend Isermann
Jun 6, 2015·Scientific Reports·Takanori KomadaMasafumi Takahashi
Feb 19, 2016·American Journal of Physiology. Renal Physiology·Wei GongAihua Zhang
Jun 6, 2016·Kidney International·Isis Ludwig-PortugallChristian Kurts
Nov 15, 2016·Nature Chemical Biology·Sebastian DollMarcus Conrad
Mar 2, 2018·Cell Death & Disease·Sonia MissiroliCarlotta Giorgi
Sep 27, 2018·Kidney Research and Clinical Practice·Fedor KundertHans-Joachim Anders
Nov 30, 2018·Frontiers in Immunology·Su-Mi KimJu-Young Moon
Mar 14, 2019·Frontiers in Physiology·Pengxu LeiYuling Sun
Apr 30, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Melania Guerrero-HueJuan Antonio Moreno

❮ Previous
Next ❯

Citations

Apr 1, 2021·Medicine and Science in Sports and Exercise·Chao LiuXuefeng Sun

❮ Previous
Next ❯

Methods Mentioned

BETA
MDA
Assay
Knockdown
flow cytometry
Fluorescence

Software Mentioned

SPSS
GraphPad Prism

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis