Proteomic Analysis of Kidney in Rats Chronically Exposed to Monosodium Glutamate

Abstract

BackgroundChronic monosodium glutamate (MSG) intake causes kidney dysfunction and renal oxidative stress in the animal model. To gain insight into the renal changes induced by MSG, proteomic analysis of the kidneys was performed.MethodsSix week old male Wistar rats were given drinking water with or without MSG (2 mg/g body weight, n = 10 per group) for 9 months. Kidneys were removed, frozen, and stored at –75°C. After protein extraction, 2-D gel electrophoresis was performed and renal proteome profiles were examined with Colloidal Coomassie Brilliant Blue staining. Statistically significant protein spots (ANOVA, p<0.05) with 1.2-fold difference were excised and analyzed by LC-MS. Proteomic data were confirmed by immunohistochemistry and Western blot analyses.ResultsThe differential image analysis showed 157 changed spots, of which 71 spots were higher and 86 spots were lower in the MSG-treated group compared with those in the control group. Eight statistically significant and differentially expressed proteins were identified: glutathione S-transferase class-pi, heat shock cognate 71 kDa, phosphoserine phosphatase, phosphoglycerate kinase, cytosolic glycerol-3-phosphate dehydrogenase, 2-amino-3-carboxymuconate-6-semialdehyde decarboxylase, α-ketoglutarate dehydrogenase and succinyl-CoA ligase.ConclusionThe identified proteins are mainly related to oxidative stress and metabolism. They provide a valuable clue to explore the mechanism of renal handling and toxicity on chronic MSG intake.

Proteomic analysis of 3-MCPD and 3-MCPD dipalmitate-induced toxicity in rat kidney

“…Gstp1 appears to be a sensitive early marker for kidney injury by 3-MCPD or 3-MCPD dipalmitate. Of note, Gstp1 was also identified as deregulated after exposure of rats to monosodium glutamate (Sharma et al 2014), indicating that Gstp1 might be suited as a molecular marker for kidney injury in the rat.…”

Answer to letter sent by Dr. M.D. Rogers (Chairman of the International Glutamate Technical Committee (IGTC), Belgium) related to Ataseven et al. article published in Food and Chemical Toxicology 2016; 91:8–18

“…This concentration was also toxic to liver and kidneys in rat experiments (Appaiah, 2010). Sharma et al (2014) performed proteomic analysis of the kidneys in wistar rats to gain insight into the renal changes induced by MSG. The differential image analysis showed 157 changed spots, of which 71 spots were higher and 86 spots were lower in the MSGtreated group compared with those in the control group.…”

“…Also, there is now evidence that excessive NMDA receptor activation is toxic for renal cells. However, approaches utilizing high throughput in vitro methods are crucial (Sharma et al, 2014).…”

Proteomic analysis of rat kidney under maleic acid treatment by SWATH‐MS technology

“…Relatedly, when Verani et al used electron microscopy to observe the morphology of rat kidneys affected by high doses of MA, they found that the structure of the mitochondria in the renal tubular cells was changed, which led them to speculate that adenosine triphosphate (ATP) synthesis and Na+/K+ ATPase may be affected, with their decreased activity eventually leading to tubular necrosis . Haviv et al investigated the type II Na‐Pi cotransport system (NaPi‐2) in the kidney of rats with MA‐induced Fanconi syndrome and found that diacid inhibits NaPi‐2 mRNA and NaPi‐2 protein in the proximal convoluted tubules, an effect that is presumably related to Na‐K‐ATPase activity and endothelial cell phosphorylation and plays a part in the oxidative metabolic pathway . In another study, Zager et al showed that MA induced lactate dehydrogenase (LDH) release, ATP reduction, and non‐esterified fatty acid (NEFA) accumulation leading to renal tubular hypoxic necrosis in CD‐1 mice .…”