Loss of calpain 10 causes mitochondrial dysfunction during chronic hyperglycemia.

Archives of Biochemistry and Biophysics
Matthew A SmithRick G Schnellmann

Abstract

We showed that renal calpain 10, a mitochondrial and cytosolic Ca(2+)-regulated cysteine protease, is specifically decreased in kidneys of diabetic rats and mice, and is associated with diabetic nephropathy. The goals of this study were to examine renal calpain 10 and mitochondrial dysfunction in streptozotocin-induced hyperglycemic rats and determine the effects of siRNA-mediated knock down of renal calpain 10 on mitochondrial function. Four weeks after streptozotocin injection, calpain 10 protein and mRNA were decreased and calpain 10 substrates accumulated. We detected increased state 2 respiration in isolated renal mitochondria and increased markers of mitochondrial fission and mitophagy. All changes were prevented by daily insulin injection. Compared to scrambled siRNA, calpain 10 siRNA resulted in a marked decrease in renal calpain 10 at 2, 5 and 7 days. In concert with the loss of renal calpain 10, calpain 10 substrates accumulated, mitochondrial fusion decreased, mitochondrial fission and mitophagy increased. In summary, insulin-sensitive hyperglycemia induced loss of renal calpain 10 is correlated with renal mitochondrial dysfunction, fission and mitophagy, and specific depletion of renal calpain 10 produces similar mi...Continue Reading

References

Aug 28, 2001·Diabetes·S K SreenanK S Polonsky
Aug 29, 2002·Nature Cell Biology·Daniela A Bota, Kelvin J A Davies
Jan 30, 2004·Diabetes·Koichi SuzukiHiroyuki Sorimachi
Jan 22, 2005·Science·Bradford B Lowell, Gerald I Shulman
Jan 26, 2010·Nature Cell Biology·Sven GeislerWolfdieter Springer
Mar 30, 2010·American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation·Steven G Coca

❮ Previous
Next ❯

Citations

Aug 24, 2013·Cell Structure and Function·Taku OzakiSei-ichi Ishiguro
Mar 19, 2014·Pathophysiology : the Official Journal of the International Society for Pathophysiology·Muthuraman PanduranganSoo-Hyun Cho
Feb 11, 2014·Archives of Medical Research·Pablo PánicoPatricia Ostrosky-Wegman
May 16, 2015·Current Diabetes Reports·Ivan Tkáč
Apr 22, 2017·The Journal of Endocrinology·Alpana MathurPoonam Kakkar
Apr 12, 2014·British Journal of Pharmacology·G C Higgins, M T Coughlan
Sep 10, 2020·Frontiers in Physiology·Zhenying ZuoHua-Feng Liu
Feb 7, 2021·International Journal of Molecular Sciences·Chunling HuangCarol A Pollock
Dec 29, 2020·Frontiers in Pharmacology·Swayam Prakash SrivastavaJulie E Goodwin
Aug 27, 2021·Experimental Cell Research·Irena AudzeyenkaAgnieszka Piwkowska

❮ Previous
Next ❯

Related Concepts

Related Feeds

Autophagy & Model Organisms

Autophagy is a cellular process that allows degradation by the lysosome of cytoplasmic components such as proteins or organelles. Here is the latest research on autophagy & model organisms

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

ATP Synthases

ATP synthases are enzymes located in the inner mitochondrial membrane that catalyze the synthesis of ATP during cellular respiration. Discover the latest research on ATP synthases here.