Taurine Supplementation Alleviates Puromycin Aminonucleoside Damage by Modulating Endoplasmic Reticulum Stress and Mitochondrial-Related Apoptosis in Rat Kidney

Abstract

Taurine (TAU) is a sulfur-containing beta amino acid that is not involved in protein composition and anabolism, conditionally essential in mammals provided through diet. Growing evidence supports a protective role of TAU supply in osmoregulation, calcium flux, and reduction of inflammation and oxidant damage in renal diseases like diabetes. Endoplasmic reticulum (ER) stress, due to abnormal proteostasis, is a contributor to nephrotic syndrome and related renal damage. Here, we investigated the effect of dietary TAU (1.5% in drinking water for 15 days) in an established rat model that mimics human minimal change nephrosis, consisting of a single puromycin aminonucleoside (PAN) injection (intraperitoneally 15 mg/100 g body weight), with sacrifice after eight days. TAU limited proteinuria and podocytes foot processes effacement, and balanced slit diaphragm nephrin and glomerular claudin 1 expressions. In cortical proximal tubules, TAU improved lysosomal density, ER perimeter, restored proper ER-mitochondria tethering and mitochondrial cristae, and decreased inflammation. Remarkably, TAU downregulated glomerular ER stress markers (GRP78, GRP94), pro-apoptotic C/EBP homologous protein, activated caspase 3, tubular caspase1, and mitochondrial chaperone GRP75, but maintained anti-apoptotic HSP25. In conclusion, TAU, by targeting upstream ER stress separate from mitochondria dysfunctions at crucial renal sites, might be a promising dietary supplement in the treatment of the drug-resistant nephrotic syndrome.

The Protective Effect of Basic Fibroblast Growth Factor on Diabetic Nephropathy Through Remodeling Metabolic Phenotype and Suppressing Oxidative Stress in Mice

“…Taurine is one of abundant free amino acids in mammals' tissues and implicated in oxidative damage, endoplasmic reticulum stress, and apoptosis (Timbrell et al, 1995;Jong et al, 2017). Hence, taurine has been reported to protect against kidney injure (Adedara et al, 2017;Stacchiotti et al, 2018;Adedara et al, 2019). In the present study, db/db mice had a significantly lower level of renal taurine than age-matched wt mice, but its level was significantly increased after bFGF treatment.…”

Effects of endoplasmic reticulum stress, liver function, insulin resistance and vascular endothelial function in patients with nonalcoholic fatty liver disease

“…It also has magnesium ion-dependent ATPase activity. The unfolded polypeptide chains can be combined to prevent protein accumulation, help protein folding, stretching, assembly and transport, thereby preventing the secretion of misfolded proteins (20)(21)(22). Therefore, GRP94 is also an important marker of ERS and acts a part in lipid and protein metabolism.…”

Taurine represses age‐associated gut hyperplasia in Drosophila via counteracting endoplasmic reticulum stress

“…To ensure proper organ development, individuals need extra taurine from the daily diet (Jung & Choi, 2019). Previous studies have reported that several diseases, including diabetes, heart failure, muscle and inflammatory diseases, and metabolic diseases, are associated with taurine deficiency (Schaffer & Kim, 2018; Stacchiotti et al, 2018). However, whether taurine deficiency also occurs during intestinal aging remains unknown.…”