Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Glutamate-induced excitotoxicity has been proposed to mediate the death of retinal ganglion cells in glaucoma. The metabolic dependence of glutamatergic neurons upon glia via the glutamate/glutamine cycle to provide the precursor for neurotransmitter glutamate is well established. Thus, the aim of the present work was to study the retinal glutamate/glutamine activity in eyes with hypertension induced by intracameral injections of hyaluronic acid (HA). For this purpose, weekly injections of HA were performed unilaterally in the rat anterior chamber, whereas the contralateral eye was injected with saline solution. At 3 or 10 weeks of treatment, glutamate and glutamine uptake and release were assessed using [3H]-glutamate and [3H]-glutamine as radioligands, respectively. In addition, glutamine synthetase activity was assessed by a spectrophotometric assay, whereas glutaminase activity was measured through the conversion of [3H]-glutamine to [3H]-glutamate. At 3 weeks of treatment with HA, a significant decrease (P<0.01) in glutamate uptake and glutamine synthetase activity was observed. Glutamine uptake and release, as well as glutaminase activity, were significantly increased (P<0.01) in eyes injected with HA for 3 weeks compared with vehicle-injected eyes, whereas [3H]-glutamate release did not change in hypertensive eyes. Only the changes in glutamine synthetase activity persisted at 10 weeks of treatment with HA. These results indicate a significant alteration in the retinal glutamate/glutamine cycle activity in hypertensive eyes. Since these changes preceded both functional and histological alterations induced by ocular hypertension, these results support the involvement of glutamate in glaucomatous neuropathy.
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PMID:Effect of glaucoma on the retinal glutamate/glutamine cycle activity. 1587 62

In patients with liver failure hyperammonemia is associated with the development of hepatic encephalopathy (HE) and immune impairment. Treatment of hyperammonemia is an unmet clinical need. Ornithine phenylacetate (OP) is a novel drug that is targeted at reducing ammonia concentration in patients with liver disease and therefore a potential treatment for HE. This review describes the mechanism of action of OP and its effect on plasma ammonia levels, brain function and inflammation of OP in both acute and chronic liver failure. Ammonia levels could shown to be reduced for up to 24 h in animal models until 120 h in patients with repeated dosing of the drug. Reduction of plasma ammonia levels is due to the stimulation of ammonia removal in the form of glutamine (through glutamine synthetase), the direct excretion of ammonia in the form phenylacetylglutamine and to a normalisation of glutaminase activity in the gut. Administration of OP is associated with a reduction of brain oedema in rats with chronic bile duct ligation and diminution of intracranial hypertension in a pig model of ALF. Studies to date have indicated that it is safe in humans and trials in overt HE are underway to establish OP as a treatment for this major complication of liver disease.
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PMID:Ornithine phenylacetate revisited. 2345 16

Emerging evidence indicates that l-glutamine (Gln) plays a fundamental role in cardiovascular physiology and pathology. By serving as a substrate for the synthesis of DNA, ATP, proteins, and lipids, Gln drives critical processes in vascular cells, including proliferation, migration, apoptosis, senescence, and extracellular matrix deposition. Furthermore, Gln exerts potent antioxidant and anti-inflammatory effects in the circulation by inducing the expression of heme oxygenase-1, heat shock proteins, and glutathione. Gln also promotes cardiovascular health by serving as an l-arginine precursor to optimize nitric oxide synthesis. Importantly, Gln mitigates numerous risk factors for cardiovascular disease, such as hypertension, hyperlipidemia, glucose intolerance, obesity, and diabetes. Many studies demonstrate that Gln supplementation protects against cardiometabolic disease, ischemia-reperfusion injury, sickle cell disease, cardiac injury by inimical stimuli, and may be beneficial in patients with heart failure. However, excessive shunting of Gln to the Krebs cycle can precipitate aberrant angiogenic responses and the development of pulmonary arterial hypertension. In these instances, therapeutic targeting of the enzymes involved in glutaminolysis such as glutaminase-1, Gln synthetase, glutamate dehydrogenase, and amino acid transaminase has shown promise in preclinical models. Future translation studies employing Gln delivery approaches and/or glutaminolysis inhibitors will determine the success of targeting Gln in cardiovascular disease.
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PMID:The Emerging Role of l-Glutamine in Cardiovascular Health and Disease. 3148 14