Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.6.1.44 (AGT)
 770 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The Primary Hyperoxaluria's (PH) are rare autosomal recessive disorders characterized by elevated oxalate production. PH patients suffer recurrent calcium oxalate kidney stone disease, and in severe cases end stage renal disease. Recent evidence has shown that RNA interference may be a suitable approach to reduce oxalate production in PH patients by knocking down key enzymes involved in hepatic oxalate synthesis. In the current study, wild type mice and mouse models of PH1 (AGT KO) and PH2 (GR KO) were treated with siRNA that targets hepatic LDHA. Although siRNA treatment substantially reduced urinary oxalate excretion [75%] in AGT KO animals, there was a relatively modest reduction [32%] in GR KO animals. Plasma and liver pyruvate levels significantly increased with siRNA treatment and liver organic acid analysis indicated significant changes in a number of glycolytic and TCA cycle metabolites, consistent with the known role of LDHA in metabolism. However, siRNA dosing data suggest that it may be possible to identify a dose that limits changes in liver organic acid levels, while maintaining a desired effect of reducing glyoxylate to oxalate synthesis. These results suggest that RNAi mediated reduction of hepatic LDHA may be an effective strategy to reduce oxalate synthesis in PH, and further analysis of its metabolic effects should be explored. Additional studies should also clarify in GR KO animals whether there are alternate enzymatic pathways in the liver to create oxalate and whether tissues other than liver contribute significantly to oxalate production.
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PMID:Reduction in urinary oxalate excretion in mouse models of Primary Hyperoxaluria by RNA interference inhibition of liver lactate dehydrogenase activity. 3136 38

Hypertension is one of the most common cardiovascular diseases, resulting in serious complications such as cardiovascular damage and chronic kidney disease. Tianshu capsule (TSC), composed of Chuanxiong (Ligusticum chuanxiong Hort) and Tianma (Gastrodiaelata Blume), has been widely used to treat the blood stasis type of headache and migraine in clinic. Results of previous research showed its antihypertensive effects, but the underlying mechanisms were still unclear. The purpose of this study was to evaluate the antihypertensive effect of TSC on spontaneously hypertensive rats by 1H NMR-based metabonomics and enzyme-linked immunosorbent assay (ELIAS), explore potential biomarkers and targets, and probe the potential mechanism of TSC on antihypertensive treatment. The results showed that TSC could decrease the product of oxidative stress (MDA) and enhance the activities of SOD and GSH-Px, down-regulate the expression of enzymes (LDHA, PKM2 and HK2) related to glycolysis, and perturb the levels of a series of amino acids (isoleucine, alanine, asparagine, citrate, etc.) and pathways. Multivariate statistical analyses showed remarkable changes in some endogenous metabolites after administrating TSC related to oxidative stress, amino acid metabolism and energy metabolism disturbances. Some enzymes (alanine-glyoxylate aminotransferase-2, tyrosine hydroxylase, dopa decarboxylase, etc.) related to metabolic biomarkers were predicted as the potential targets of TSC treatment on SHRs. The discoveries are helpful to understand the antihypertensive mechanism of TSC and provide theoretical evidence for its future research, development and clinical use.
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PMID:Effects of Tianshu Capsule on Spontaneously Hypertensive Rats as Revealed by 1H-NMR-Based Metabolic Profiling. 3157 79