Excessive endogenous oxalate synthesis can result in calcium oxalate kidney stone formation and renal failure. Hydroxyproline catabolism in the liver and kidney contributes to endogenous oxalate production in mammals. To quantify this contribution we have infused Wt mice, Agxt KO mice deficient in liver alanine:glyoxylate aminotransferase, and Grhpr KO mice deficient in glyoxylate reductase, with (13)C5-hydroxyproline. The contribution of hydroxyproline metabolism to urinary oxalate excretion in Wt mice was 22±2%, 42±8% in Agxt KO mice, and 36%±9% in Grhpr KO mice. To determine if blocking steps in hydroxyproline and glycolate metabolism would decrease urinary oxalate excretion, mice were injected with siRNA targeting the liver enzymes glycolate oxidase and hydroxyproline dehydrogenase. These siRNAs decreased the expression of both enzymes and reduced urinary oxalate excretion in Agxt KO mice, when compared to mice infused with a luciferase control preparation. These results suggest that siRNA approaches could be useful for decreasing the oxalate burden on the kidney in individuals with Primary Hyperoxaluria.
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http://dx.doi.org/10.1016/j.bbadis.2015.12.001 | DOI Listing |
Mol Ther
October 2024
Shanghai Frontiers Science Center of Genome Editing and Cell Therapy, Shanghai 200241, China; Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai 200241, China; YolTech Therapeutics, Shanghai 201109, China. Electronic address:
Nat Metab
October 2024
Department of Pathology and Translational Pathobiology, Louisiana State University Health Sciences Center-Shreveport, Shreveport, LA, USA.
The incidence of metabolic dysfunction-associated steatohepatitis (MASH) is on the rise, and with limited pharmacological therapy available, identification of new metabolic targets is urgently needed. Oxalate is a terminal metabolite produced from glyoxylate by hepatic lactate dehydrogenase (LDHA). The liver-specific alanine-glyoxylate aminotransferase (AGXT) detoxifies glyoxylate, preventing oxalate accumulation.
View Article and Find Full Text PDFJ Cell Physiol
November 2024
Department of Molecular Research, Sri Shankara Cancer Hospital and Research Centre, Bangalore, India.
Colon cancer is on the rise in younger adults. Despite multimodal treatment strategies, clinical outcomes in advanced stage colon cancer patients remain poor. Neoadjuvant/adjuvant chemotherapy efficacy is limited due to chemoresistance, toxicity, and negative side effects.
View Article and Find Full Text PDFJ Hepatocell Carcinoma
August 2024
Department of Laboratory Medicine, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, People's Republic of China.
Purpose: Alanine glyoxylate aminotransferase (AGXT) family members are crucial in cancer processes, but their role in hepatocellular carcinoma (HCC) metabolism is unclear. This study investigates AGXT2's function in HCC.
Patients And Methods: AGTX2 expression was studied using bioinformatics, real-time reverse transcriptase-polymerase chain reaction (RT-qPCR), Western blot, and Enzyme-linked immunosorbent assay (ELISA).
Food Chem Toxicol
July 2023
Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, Tongji Medical College, Huazhong University of Science and Technology, Hangkong Road 13, Wuhan, 430030, China; Department of Nutrition and Food Hygiene, MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Hangkong Road 13, Wuhan, 430030, China. Electronic address:
Mercury is one heavy metal toxin that could cause severe health impairments. Mercury exposure has become a global environmental issue. Mercury chloride (HgCl) is one of mercury's main chemical forms, but it lacks detailed hepatotoxicity data.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!