Effect of endoplasmic reticulum stress inhibition on hyperoxaluria-induced oxidative stress: influence on cellular ROS sources

Bhardwaj, Rishi; Tandon, Chanderdeep; Dhawan, Devinder; Kaur, Tanzeer
December 2017
World Journal of Urology;Dec2017, Vol. 35 Issue 12, p1955
Academic Journal
Purpose: Hyperoxaluria-induced calcium oxalate crystallisation is associated with the generation of reactive oxygen species (ROS) via mitochondria and NADPH oxidase. Endoplasmic reticulum (ER) has emerged as an organelle which could influence mitochondrial functioning and ROS generation. Plugging an upstream pathway of mitochondrial and NADPH oxidase-induced ROS generation may have better prophylaxis. Therefore, we propose to investigate the linkage of hyperoxaluria-induced ROS generation with ER stress by inhibiting the later with 4-Phenylbutyric acid (4-PBA). Methods: Male wistar rats were divided into three groups: a normal control group, an ethylene glycol with ammonium chloride-induced hyperoxaluric group (EA) and a third group which has hyperoxaluric animals given 4-PBA at a dose of 300 mg/kg. After 9 days of treatment, animals were sacrificed and renal tissues were analysed for histopathological examination, ROS, mitochondrial dysfunction, ER stress markers, inflammatory markers and NADPH oxidase subunits expression. Results: Hyperoxaluric rats exhibited a significant increase in the levels of ROS, subsequently up-regulated levels of ER stress markers, inflammatory indicators, NADPH oxidase subunits and compromised mitochondrial functioning. However, ER stress amelioration appreciably curtailed the alterations caused by hyperoxaluric abuse. Conclusions: Therefore, suggesting the major role of ER in hyperoxaluric manifestations thereby providing an opportunity to target ER stress for future therapeutic interventions.


Related Articles

  • Mitochondrial reactive oxygen species (ROS) inhibition ameliorates palmitate-induced INS-1 beta cell death. Lin, Ning; Chen, Hanbei; Zhang, Hongmei; Wan, Xiaoyu; Su, Qing // Endocrine (1355008X);Aug2012, Vol. 42 Issue 1, p107 

    The purpose of this study is to explore the possible link between oxidative stress and endoplasmic reticulum (ER) stress in palmitate (PA) induced apoptosis of INS-1 cells, and to figure out the main source of reactive oxygen species (ROS) and the effect of ROS inhibition on the level of ER...

  • Mitochondrial ROS fuel the inflammasome. Sorbara, Matthew T; Girardin, Stephen E // Cell Research;Apr2011, Vol. 21 Issue 4, p558 

    The article presents a study by Zhou and colleagues which shows that mitochondrial reactive oxygen species (ROS) generation leads to activation of Nod-like receptor protein 3 (NLRP3) inflammasome. The study shows that macrophage treatment with NLRP3 activators results to NLRP3's recruitment to...

  • H2O2-mediated modulation of cytosolic signaling and organelle function in rat hippocampus. Gerich, Florian J.; Funke, Frank; Hildebrandt, Belinda; Faßhauer, Martin; Müller, Michael // Pflugers Archiv European Journal of Physiology;Sep2009, Vol. 458 Issue 5, p937 

    Reactive oxygen species (ROS) released from (dys-)functioning mitochondria contribute to normal and pathophysiological cellular signaling by modulating cytosolic redox state and redox-sensitive proteins. To identify putative redox targets involved in such signaling, we exposed hippocampal...

  • An Involvement of Oxidative Stress in Endoplasmic Reticulum Stress and Its Associated Diseases. Bhandary, Bidur; Marahatta, Anu; Hyung-Ryong Kim; Han-Jung Chae // International Journal of Molecular Sciences;Jan2013, Vol. 14 Issue 1, p434 

    The endoplasmic reticulum (ER) is the major site of calcium storage and protein folding. It has a unique oxidizing-folding environment due to the predominant disulfide bond formation during the process of protein folding. Alterations in the oxidative environment of the ER and also intra-ER Ca2+...

  • Sigma-1 Receptor Chaperone at the ER-Mitochondrion Interface Mediates the Mitochondrion-ER-Nucleus Signaling for Cellular Survival. Mori, Tomohisa; Hayashi, Teruo; Hayashi, Eri; Su, Tsung-Ping // PLoS ONE;Oct2013, Vol. 8 Issue 10, p1 

    The membrane of the endoplasmic reticulum (ER) of a cell forms contacts directly with mitochondria whereby the contact is referred to as the mitochondrion-associated ER membrane or the MAM. Here we found that the MAM regulates cellular survival via an MAM-residing ER chaperone the sigma-1...

  • Apoptotic crosstalk between the endoplasmic reticulum and mitochondria controlled by Bcl-2. Häcki, Jürg; Egger, Lotti; Monney, Laurent; Conus, Sébastien; Rossé, Thierry; Fellay, Isabelle; Borner, Christoph // Oncogene;5/4/2000, Vol. 19 Issue 19, p2286 

    Apoptosis involves mitochondrial steps such as the release of the apoptogenic factor cytochrome c which are effectively blocked by Bcl-2. Although Bcl-2 may have a direct action on the mitochondrial membrane, it also resides and functions on the endoplasmic reticulum (ER), and there is...

  • Endoplasmic reticulum localized Bcl-2 prevents apoptosis when redistribution of cytochrome c is a late event. Annis, Matthew G; Zamzami, Naoufal; Zhu, Weijia; Penn, Linda Z; Kroemer, Guido; Leber, Brian; Andrews, David W // Oncogene;4/12/2001, Vol. 20 Issue 16, p1939 

    The disruption of mitochondrial function is a key component of apoptosis in most cell types. Localization of Bcl-2 to the outer mitochondrial and endoplasmic reticulum membranes is consistent with a role in the inhibition of many forms of apoptosis. In Rat-1 cells, a Bcl-2 mutant targeted...

  • Dissecting the pathways to death. Daniel, P T // Leukemia (08876924);Dec2000, Vol. 14 Issue 12, p2035 

    This report summarizes recent findings in the field of basic and translational apoptosis research which were presented at the 1st Conference on 'Mechanisms of Cell Death and Disease: Advances in Therapeutic Intervention' organized by the European School of Hematology and the University of Texas...

  • Effect of Bax deficiency on death receptor 5 and mitochondrial pathways during endoplasmic reticulum calcium pool depletion-induced apoptosis. He, Qin; Montalbano, JoAnne; Corcoran, Chad; Jin, Weixin; Huang, Ying; Sheikh, M Saeed // Oncogene;5/1/2003, Vol. 22 Issue 17, p2674 

    Thapsigargin (TG), by inducing perturbations in cellular Ca2+ homeostasis, can induce apoptosis, but the molecular mechanisms remain to be fully elucidated. We have recently reported that TG-induced apoptosis appears to involve the DR5-dependent apoptotic pathway that cross talks with the...

  • Mitochondrial fission: ER marks the spot. Chenette, Emily J. // Nature Cell Biology;Oct2011, Vol. 13 Issue 10, p1188 

    The article focuses on the study by Voeltz and colleagues regarding mitochondrial fission which occurs at the sites of endoplasmic reticulum (ER)-mitochondria contact, in which they a high-resolution of the contact sites showed that ER wraps around the mitochondria to create constrictions.


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics