Journal Article

PRE-084 ameliorated kidney injury by reducing endoplasmic reticulum stress in the rat model of adenine-induced chronic kidney disease

Mathesh, Karikalan, Parida, Subhashree, Lingaraju, Madhu Cholenahalli, Manickam, Kesavan, Kumaran, Mohanapriya, Kumar, Dinesh, Singh, Thakur Uttam, Srivastava, Vivek

2023

Overview

Background Endoplasmic reticulum (ER) stress plays an important role in the development of chronic kidney disease (CKD). Sigma-1 receptors (σ1Rs) are novel chaperone proteins that regulate ER stress. However, effect of σ1R activation on renal ER stress is yet unexplored. So, in the present study we investigated the effects of PRE-084, a σ1R agonist on renal injury and ER stress in the rat model of CKD. Methods CKD group rats were fed adenine for 28 days and CKD treatment group rats were additionally administered PRE-084 intraperitoneally at 1, 3 and 10 mg/kg body weight dose from Day 22–28. ER stress markers were evaluated using molecular biology techniques such as immunohistochemistry and Western blot. Results Marked kidney injury was observed in CKD rats as revealed by biochemical and histological findings. Expression of ER stress proteins such as phosphorylated protein kinase R-like ER kinase (p-PERK), cleaved activating transcription factor-6 (ATF-6f), phosphorylated inositol requiring enzyme1α (p-IRE1α) and caspase-12 were higher in CKD rats. Nevertheless, CKD rats treated with PRE-084 particularly at 10 mg/kg dose showed considerably lesser kidney injury along with higher expression of σ1R and marked reduction of all the ER stress proteins studied. Conclusion Results reveal that PRE-084 likely ameliorated the adenine-induced kidney injury by lowering ER stress through increased σ1R expression.

• Publisher: Springer Netherlands,Springer Nature B.V
• Subject: Adenine / agonists / Animal Anatomy / Animal Biochemistry / animal models / Animals / Apoptosis / Biomedical and Life Sciences / Body weight / Caspase-12 / Endoplasmic reticulum / Endoplasmic Reticulum Stress / Endoribonucleases - metabolism / Heat-Shock Proteins - metabolism / Histology / Immunohistochemistry / Inositol / inositols / Kidney - metabolism / Kidney diseases / kidneys / Kinases / Life Sciences / molecular biology / Morphology / Original Article / Protein kinase R / protein kinases / Protein Serine-Threonine Kinases - metabolism / Proteins / Rats / Renal Insufficiency, Chronic - chemically induced / Renal Insufficiency, Chronic - drug therapy / Renal Insufficiency, Chronic - metabolism / Stress proteins / Western blotting