Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.23.5 (cathepsin D)
 4,130 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The role of lipid peroxidation (LPO) in renal tubular damage mediated calcium oxalate retention was investigated in a rat model. Hyperoxaluria, without deposition of oxalate in kidney, was induced by administration of ethylene glycol (EG), a precursor of oxalate. Oxidative stress condition was produced by administration of buthionine sulfoximine (BSO), an inhibitor of glutathione biosynthesis. BSO-treated rats showed a significant (p < 0.001) increase in LPO over EG-treated rats and it was almost doubled in BSO + EG treated rats. LPO was accompanied by significant urinary excretion of renal damage marker enzymes such as gamma-glutamyl transpeptidase (gamma-GT), alkaline phosphatase (ALP) and cathepsin D, mucoproteins, and glycosaminoglycans (GAGs) in the BSO and BSO + EG groups but not in the EG group. Urinary excretion of gamma-GT (r = +0.90) (p < 0.001) and deposition of oxalate (r = +0.78) (p < 0.001) in kidney positively correlated with LPO. These results suggest that LPO initiates renal damage, thereby leading to calcium oxalate retention and stone formation.
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PMID:Renal injury mediated calcium oxalate nephrolithiasis: role of lipid peroxidation. 915 57

Purpose: As a Chinese medicinal herb, Desmodium styracifolium (Osb.) Merr (DS) has been applied clinically to alleviate crystal-induced kidney injuries, but its effective components and their specific mechanisms still need further exploration. This research first combined the methods of network pharmacology and proteomics to explore the therapeutic protein targets of DS on oxalate crystal-induced kidney injuries to provide a reference for relevant clinical use. Methods: Oxalate-induced kidney injury mouse, rat, and HK-2 cell models were established. Proteins differentially expressed between the oxalate and control groups were respectively screened using iTRAQ combined with MALDI-TOF-MS. The common differential proteins of the three models were further analyzed by molecular docking with DS compounds to acquire differential targets. The inverse docking targets of DS were predicted through the platform of PharmMapper. The protein-protein interaction (PPI) relationship between the inverse docking targets and the differential proteins was established by STRING. Potential targets were further validated by western blot based on a mouse model with DS treatment. The effects of constituent compounds, including luteolin, apigenin, and genistein, were investigated based on an oxalate-stimulated HK-2 cell model. Results: Thirty-six common differentially expressed proteins were identified by proteomic analysis. According to previous research, the 3D structures of 15 major constituents of DS were acquired. Nineteen differential targets, including cathepsin D (CTSD), were found using molecular docking, and the component-differential target network was established. Inverse-docking targets including p38 MAPK and CDK-2 were found, and the network of component-reverse docking target was established. Through PPI analysis, 17 inverse-docking targets were linked to differential proteins. The combined network of component-inverse docking target-differential proteins was then constructed. The expressions of CTSD, p-p38 MAPK, and p-CDK-2 were shown to be increased in the oxalate group and decreased in kidney tissue by the DS treatment. Luteolin, apigenin, and genistein could protect oxalate-stimulated tubular cells as active components of DS. Conclusion: The potential targets including the CTSD, p38 MAPK, and CDK2 of DS in oxalate-induced kidney injuries and the active components (luteolin, apigenin, and genistein) of DS were successfully identified in this study by combining proteomics analysis, network pharmacology prediction, and experimental validation.
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PMID:Exploring the Therapeutic Mechanism of Desmodium styracifolium on Oxalate Crystal-Induced Kidney Injuries Using Comprehensive Approaches Based on Proteomics and Network Pharmacology. 2995 Sep 96