Liver argininosuccinate synthase binds to bacterial lipopolysaccharides and lipid A and inactivates their biological activities

Satoh, Masaharu; Iwahori, Tsuguya; Sugawara, Naoki; Yamazaki, Masatoshi

doi:10.1179/096805106x89062

Cited by 11 publications

(13 citation statements)

References 57 publications

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“…Endogenous synthesis of L-arginine is limited by activities of ASS and ASL and the availability of aspartate and citrulline. ASS is the rate-limiting step in the conversion of citrulline to L-arginine (El-Hattab et al, 2012;Haines et al, 2011;Morris, 1992;Satoh et al, 2006). ASL has a structural role in promoting NOS activity in addition to its role as the only enzyme that can generate L-arginine endogenously (Erez et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

“…Aspartate aminotransferase (AST) activity and NO synthase activity were determined using kits purchased from the Nanjing Jiangcheng Bioengineering Institute. Enzyme activity of argininosuccinate synthase and fumarase was measured based on previously reported methods (Satoh et al, 2006;Tian et al, 2009). Arginase activity was measured as the conversion of L-arginine to L-ornithine based on a previously reported method (Ochoa et al, 2000).…”

Section: Enzymatic Activity Assaysmentioning

confidence: 99%

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Malate and Aspartate Increase L-Arginine and Nitric Oxide and Attenuate Hypertension

et al. 2017

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Fumarase catalyzes the interconversion of fumarate and L-malate in the tricarboxylic acid cycle. The Dahl salt-sensitive (SS) rat, a model of salt-sensitive hypertension, exhibits fumarase insufficiencies. To investigate the mechanism mediating the effect of fumarase-related metabolites on hypertension, we considered the pathway in which L-malate can be converted to oxaloacetate, aspartate, argininosuccinate, and L-arginine, the substrate of nitric oxide (NO) synthase. The levels of aspartate, citrulline, L-arginine, and NO were significantly decreased in the kidneys of SS rats compared to salt-insensitive consomic SS.13 rats. Knockdown of fumarase in human kidney cells and vascular endothelial cells resulted in decreased levels of malate, aspartate, L-arginine, and NO. Supplementation of aspartate or malate increased renal levels of L-arginine and NO and attenuated hypertension in SS rats. These findings reveal a multi-step metabolic pathway important for hypertension in which malate and aspartate may modulate blood pressure by altering levels of L-arginine and NO.

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Section: Discussionmentioning

confidence: 99%

Section: Enzymatic Activity Assaysmentioning

confidence: 99%

Malate and Aspartate Increase L-Arginine and Nitric Oxide and Attenuate Hypertension

et al. 2017

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“…Lipid A is the endotoxic portion of LPS. ASS1 physically binds to the lipid A portion of LPS, inactivates the biological activity and clears circulating LPS (39,40). ASS1 was reported to be upregulated in rat hepatocytes by chronic ethanol feeding (21).…”

Section: Discussionmentioning

confidence: 99%

Dietary fat sources differentially modulate intestinal barrier and hepatic inflammation in alcohol-induced liver injury in rats

Zhong

Xie

et al. 2013

American Journal of Physiology-Gastrointestinal and Liver Physi

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toxemia is a causal factor in the development of alcoholic liver injury. The present study aimed at determining the interactions of ethanol with different fat sources at the gut-liver axis. Male Sprague-Dawley rats were pair fed control or ethanol liquid diet for 8 wk. The liquid diets were based on a modified Lieber-DeCarli formula, with 30% total calories derived from corn oil (rich in polyunsaturated fatty acids). To test the effects of saturated fats, corn oil in the ethanol diet was replaced by either cocoa butter (CB, rich in long-chain saturated fatty acids) or medium-chain triglycerides (MCT, exclusively medium-chain saturated fatty acids). Ethanol feeding increased hepatic lipid accumulation and inflammatory cell infiltration and perturbed hepatic and serum metabolite profiles. Ethanol feeding with CB or MCT alleviated ethanol-induced liver injury and attenuated ethanolinduced metabolic perturbation. Both CB and MCT also normalized ethanol-induced hepatic macrophage activation, cytokine expression, and neutrophil infiltration. Ethanol feeding elevated serum endotoxin level, which was normalized by MCT but not CB. In accordance, ethanol-induced downregulations of intestinal occludin and zonula occludens-1 were normalized by MCT but not CB. However, CB normalized ethanol-increased hepatic endotoxin level in association with upregulation of an endotoxin detoxifying enzyme, argininosuccinate synthase 1 (ASS1). Knockdown ASS1 in H4IIEC3 cells resulted in impaired endotoxin clearance and upregulated cytokine expression. These data demonstrate that the protection of saturated fats against alcohol-induced liver injury occur via different actions at the gut-liver axis and are chain length dependent. alcohol; saturated fat; endotoxemia; inflammation; liver injury ALCOHOLIC LIVER DISEASE (ALD) is a major health problem worldwide (19,41). Endotoxemia is closely associated with the pathogenesis of ALD through the stimulation of proinflammatory cytokine production (6, 37). Significantly increased levels of endotoxin were found in both alcoholic patients and experimental animal models of ALD, and the levels correlated well with the development of liver injury (7). Our previous study showed that neutralization of endotoxin by endotoxin neutralizing protein attenuates acute alcohol-induced cytokine production and liver injury, suggesting the importance of endotoxins in mediating alcoholic hepatotoxicity (51). Mechanistic studies have suggested that intestinal bacterial overgrowth and intestinal permeability increase contribute to the development of endotoxemia in alcoholics (35, 37). Our previous work showed that orally administrated lipopolysaccharide was detectable in the plasma of alcohol-intoxicated mice but not in control mice (52), providing direct evidence that alcohol increases gut permeability to endotoxins. Animal studies also showed that prevention of gut leakiness resulted in suppression of alcohol exposure-induced endotoxemia and liver damage (18, 44), suggesting that gut leakiness is a causal factor in the...

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“…A number of ASS forms with different pI values have previously been described from rat liver. 238 ASS has been shown to bind bacterial lipopolysaccharides, 239 and could perhaps play a role in the autophagic defense against infective microorganisms (xenophagy). [240][241][242] Arginase 1 was identified in three different spots: two of these (no.…”

Section: Autophagosomal Membrane Proteinsmentioning

confidence: 99%

Proteomic Analysis of Membrane-Associated Proteins from Rat Liver Autophagosomes

Øverbye¹,

Fengsrud²,

Seglen³

2007

Autophagy

140

117

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Liver argininosuccinate synthase binds to bacterial lipopolysaccharides and lipid A and inactivates their biological activities

Cited by 11 publications

References 57 publications

Malate and Aspartate Increase L-Arginine and Nitric Oxide and Attenuate Hypertension

Malate and Aspartate Increase L-Arginine and Nitric Oxide and Attenuate Hypertension

Dietary fat sources differentially modulate intestinal barrier and hepatic inflammation in alcohol-induced liver injury in rats

Proteomic Analysis of Membrane-Associated Proteins from Rat Liver Autophagosomes

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