Caspase-1, but Not Caspase-3, Promotes Diabetic Nephropathy

Journal of the American Society of Nephrology : JASN
Khurrum ShahzadBerend Isermann

Abstract

Glomerular apoptosis may contribute to diabetic nephropathy (dNP), but the pathophysiologic relevance of this process remains obscure. Here, we administered two partially disjunct polycaspase inhibitors in 8-week-old diabetic (db/db) mice: M-920 (inhibiting caspase-1, -3, -4, -5, -6, -7, and -8) and CIX (inhibiting caspase-3, -6, -7, -8, and -10). Notably, despite reduction in glomerular cell death and caspase-3 activity by both inhibitors, only M-920 ameliorated dNP. Nephroprotection by M-920 was associated with reduced renal caspase-1 and inflammasome activity. Accordingly, analysis of gene expression data in the Nephromine database revealed persistently elevated glomerular expression of inflammasome markers (NLRP3, CASP1, PYCARD, IL-18, IL-1β), but not of apoptosis markers (CASP3, CASP7, PARP1), in patients with and murine models of dNP. In vitro, increased levels of markers of inflammasome activation (Nlrp3, caspase-1 cleavage) preceded those of markers of apoptosis activation (caspase-3 and -7, PARP1 cleavage) in glucose-stressed podocytes. Finally, caspase-3 deficiency did not protect mice from dNP, whereas both homozygous and hemizygous caspase-1 deficiency did. Hence, these results suggest caspase-3-dependent cell death...Continue Reading

References

Jan 29, 1999·FEBS Letters·P SchotteR Beyaert
Mar 23, 2001·Nature Immunology·R S HotchkissI E Karl
May 6, 2004·Molecular and Cellular Biochemistry·Dinender KumarKevin D Burns
Jan 25, 2005·Cell Death and Differentiation·U Fischer, K Schulze-Osthoff
Mar 24, 2005·Infection and Immunity·Susan L Fink, Brad T Cookson
Aug 16, 2006·American Journal of Respiratory and Critical Care Medicine·Anasuya SarkarMark D Wewers
Apr 19, 2008·Biochemical and Biophysical Research Communications·Guanghui LiuZhiming Ge
Aug 16, 2008·Reviews in Endocrine & Metabolic Disorders·Sebastian MartiniMatthias Kretzler
Aug 30, 2008·The Journal of Experimental Medicine·Jonathan MaelfaitRudi Beyaert
Aug 7, 2009·Kidney International·Sang Choel LeeShin-Wook Kang
Sep 29, 2009·The International Journal of Biochemistry & Cell Biology·Mohamed Lamkanfi, Thirumala-Devi Kanneganti
Dec 3, 2010·Nature·Rongbin ZhouJürg Tschopp
Sep 3, 2011·Immunological Reviews·Edward A MiaoAlan Aderem
Oct 18, 2011·Nature·Nobuhiko KayagakiVishva M Dixit
Feb 5, 2014·Clinical Science·Harshini MudaliarUsha Panchapakesan
Jun 14, 2014·Journal of the American Society of Nephrology : JASN·Andreas LinkermannZheng Dong
Jul 31, 2014·Kidney International·Khurrum ShahzadBerend Isermann
Jan 27, 2015·Current Opinion in Immunology·Jieling YangFeng Shao
May 9, 2015·Apoptosis : an International Journal on Programmed Cell Death·Sun Ha LeeShin-Wook Kang
Jul 1, 2015·Kidney International·Gowrie BalasubramaniamBhaskar Dasgupta

❮ Previous
Next ❯

Citations

Aug 16, 2016·Journal of the American Society of Nephrology : JASN·Hans-Joachim Anders
Apr 24, 2018·Phytotherapy Research : PTR·Yao-Wu LiuTao-Yun Wang
Apr 15, 2018·Nature Reviews. Nephrology·Hans-Joachim AndersMario Schiffer
Aug 26, 2016·American Journal of Physiology. Renal Physiology·Raimund PichlerKatherine R Tuttle
Nov 13, 2018·Journal of Cellular Physiology·Habib YaribeygiAmirhossein Sahebkar
Nov 20, 2018·Current Opinion in Hematology·Khurrum ShahzadBerend Isermann
Sep 20, 2018·American Journal of Physiology. Renal Physiology·Markus M RinschenRachelle E Koch
Jul 12, 2017·Journal of the American Society of Nephrology : JASN·Andi MarquardtBerend Isermann
Nov 2, 2018·Acta Pharmacologica Sinica·Nai-Jun MiaoLi-Min Lu
May 31, 2020·International Journal of Molecular Sciences·Sandra Rayego-MateosJesús Egido
Jun 6, 2019·Nature Reviews. Nephrology·Takanori Komada, Daniel A Muruve
Feb 2, 2019·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Wanning WangLu Cai
May 24, 2019·BioMed Research International·Chenlin GaoYong Xu
Jan 17, 2020·Nature Reviews. Nephrology·Sydney C W Tang, Wai Han Yiu
Jul 28, 2020·Journal of the American Society of Nephrology : JASN·Thati MadhusudhanBerend Isermann
Feb 24, 2017·Frontiers in Immunology·Hong XiaShaolin Shi
Jan 29, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Shengfeng WanFengmin Shao
Feb 10, 2021·Cell Death & Disease·Seonghun KimJung Tak Park
Dec 16, 2018·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Mengjie SunZhihong Liu
Mar 22, 2021·Molecular Therapy : the Journal of the American Society of Gene Therapy·Hanying DingFan Fan Hou
Jul 27, 2021·Frontiers in Immunology·Wei XiongChun Zhang
Jun 17, 2021·Experimental and Therapeutic Medicine·Yulin WangLin Tang
Sep 17, 2021·Clinica Chimica Acta; International Journal of Clinical Chemistry·Abdullah Al MamunJian Xiao

❮ Previous
Next ❯

Related Concepts

Related Feeds

Autoimmune Lymphoproliferative Syndrome

Autoimmune lymphoproliferative syndrome (ALPS) is a rare genetic disorder of abnormal lymphocyte survival caused by defective Fas mediated apoptosis. Discover the latest research on ALPS here.

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

Biomarkers for Diabetes

This feed focuses on the latest research on biomarkers used for monitoring disease progression in diabetes.