Tempol reduces podocyte apoptosis via PARP signaling pathway in experimental diabetes mellitus

Nephron. Experimental Nephrology
Elisa B M I PeixotoJose B Lopes de Faria

Abstract

In diabetic hypertensive rats, tempol reduces albuminuria by restoring the redox imbalance. Increased formation of reactive oxygen species leading to activation of poly(ADP-ribose) polymerase (PARP)-1 and podocyte loss by apoptosis contribute to albuminuria in diabetes mellitus (DM). In the present study, we investigated the hypothesis that in DM tempol reduces albuminuria by inhibition of PARP-induced podocyte apoptosis. DM was induced in 4-week-old spontaneously hypertensive rats by streptozotocin. Mouse and human podocyte cell lines were cultured in normal or high-glucose conditions, with or without tempol and/or a PARP-1 inhibitor, PJ34. In diabetic rats, tempol treatment did not affect plasma glucose levels or systolic blood pressure. Albuminuria was higher in diabetic rats, and it was reduced by tempol. DM leads to an elevation of glomerular apoptotic cells and to podocyte loss; both were prevented by tempol treatment. DM increases the expression of poly(ADP-ribose)-modified proteins in isolated glomeruli, and it was reduced by tempol. In vitro, high glucose increased caspase-3 activity and led to a higher number of apoptotic cells that were prevented by tempol and the PARP-1 inhibitor. In DM, tempol reduces albuminuria a...Continue Reading

References

Aug 2, 2007·Nature Reviews. Drug Discovery·Csaba SzabóRafael Radi
Sep 1, 2007·Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology·Alexandros PapadimitriouShanta J Persaud
Mar 12, 2008·Basic & Clinical Pharmacology & Toxicology·Paola Yam-CanulJosé Pedraza-Chaverri
Jun 7, 2008·The American Journal of Pathology·Pal Pacher, Csaba Szabo
Dec 30, 2008·Pharmacological Reviews·Christopher S Wilcox, Adam Pearlman
May 13, 2009·Current Opinion in Nephrology and Hypertension·Basil O BurneyGeorge L Bakris
Mar 26, 2010·Investigative Ophthalmology & Visual Science·Mariana A B RosalesJacqueline M Lopes de Faria
Jul 14, 2010·Biochimica Et Biophysica Acta·Hanna ShevalyeIrina G Obrosova
Jan 14, 2011·Hypertension Research : Official Journal of the Japanese Society of Hypertension·José Butori Lopes de FariaJacqueline Mendonça Lopes de Faria

❮ Previous
Next ❯

Citations

Jul 30, 2014·Wound Repair and Regeneration : Official Publication of the Wound Healing Society [and] the European Tissue Repair Society·Michael P SarrasRobert V Intine
May 23, 2013·Biochemical and Biophysical Research Communications·Dong Il Kim, Soo Hyun Park
May 9, 2015·Apoptosis : an International Journal on Programmed Cell Death·Sun Ha LeeShin-Wook Kang
Jul 30, 2016·Journal of Renal Injury Prevention·Akram RanjbarFarhad Khoshjou
Feb 4, 2021·Diabetes, Metabolic Syndrome and Obesity : Targets and Therapy·Hengmei ZhuXiaojiang Zhan
Aug 10, 2021·Frontiers in Medicine·Jing XuDaisuke Koya

❮ 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.

Apoptotic Caspases

Apoptotic caspases belong to the protease enzyme family and are known to play an essential role in inflammation and programmed cell death. Here is the latest research.

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