Proteinase K inactivation of cytosolic aspartate aminotransferase isoenzyme for measurement of human serum mitochondrial aspartate aminotransferase

Watazu, Yoshifumi; Uji, Yukitaka; Okabe, Hiroaki; Shirahase, Yasushi; Kaneda, Nobuaki; Karmen, Arthur

doi:10.1002/jcla.1860070202

Cited by 3 publications

(3 citation statements)

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“…However, the measurement methods of plasma mitochondria-type ALT or cytosol-type ALT have not been established (DeRosa and Swick, 1975). Differences in the physicochemical properties between mitochondrial and cytosolic AST have been reported and the measurement methods of plasma mitochondria-type AST activity have been established (Watazu et al, 1993). Plasma lipid parameters, activities of ALT, AST and mitochondria-type AST, and liver function parameters were measured at 37°C with a Toshiba TBA-120FR automated analyzer using standard reagents and the following principle: triglycerides (TGL), GPO·DAOS method (Wako Pure Chemical, Tokyo, Japan), total cholesterol (T-CH), cholesterol oxidase·HDAOS method (Wako Pure Chemical), ALT, UV method (Wako Pure Chemical), AST, UV method (Wako Pure Chemical), mitochondria-type AST, protease method (Sysmex Corporation, Hyogo, Japan), alkaline phosphatase, pnitrophenyl phosphoric acid method (Wako Pure Chemical), lactate dehydrogenase, Wróblewski-LaDue method (Wako Pure Chemical), total bilirubin, enzyme method (Wako Pure Chemical).…”

Section: Methodsmentioning

confidence: 99%

Effects of fenofibrate on plasma and hepatic transaminase activities and hepatic transaminase gene expression in rats

et al. 2009

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-Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels are widely used as sensitive markers of possible tissue damage, particularly liver toxicity. Lipid-lowering that the phenomenon is related to drug-induced liver injury (DILI). Some in vitro studies have indicatleakage from the hepatocytes associated with cell lysis. In this study, male F344/DuCrlCrlj (Fischer) rats -macological effects, blood and hepatic transaminase activities and the gene expression of the transami--in parallel with increases in hepatic transaminase activities associated with increases in the transaminase genes in the liver and were not considered to be a consequence of hepatotoxicity from the drug. The mod--brate. The evidence obtained in our study underlines the importance of gene regulation as a possible alternative mechanism for increased blood transaminase activities.Correspondence: Akio Kobayashi (E-mail: akio.kobayashi@jt.com) Original ArticleThe Journal of Toxicological Sciences (J. Toxicol. Sci.) Vol.34, No.4, 377-387, 2009 Vol. 34 No. 4 377 sis in rabbits (Kornbrust et al., 1989). These clinical and -toxicity. Possible mechanisms for the transaminase elevation include increased transaminase synthesis, decreased transaminase clearance and transaminase leakage from hepatocytes whose membranes may have been altered by changes in their lipid content. Transaminases, both ALT and AST, are some of the key enzymes involved in amino acid/glucose metabolism pathways and play an important role in gluconeogenesis in the liver and kidney (DeRosa and Swick, 1975). Taking the functions of transaminases into account, transaminase synthesis must be altered as well as for other enzymes involved in the amino acid/ glucose metabolism pathways if hormonal or nutritional fluctuation, which leads to acceleration or deceleration of gluconeogenesis, occurs. In fact, the expression of the rat cytosolic AST gene in the hepatoma cell line Fao is modified by glucocorticoids, insulin and cAMP (Aggerbeck et al., 1993;Barouki et al., 1989) and by a protein-rich diet or during prolonged fasting (Horio et al., 1988). Further, ALT and AST levels in the serum and organs are increased by these hormonal and nutrition- et al., 1966;Ramesh and Pugalendi, 2005;Rosen et al., 1959; Hoffman et al., 1989). Elevation of transaminase activities in the serum or organs associated with hormonal or nutritional modifications are slight in mag--tive of tissue damage including hepatocellular necrosis. These nutritional or hormonal aspects for the elevation of transaminase activities have led some researchers to in vitro studies for the investigations of the relationship between transaminase activities and their gene expression in human and animal hepatocytes treated with drugs which modify lipid metabolism as their pharmacological action. Edgar et al increased ALT and AST activities in human HepG2 cells as well as both mRNA levels. Another in vitro study conducted by Tomkiewicz et al -brate increased the expression of the cytosolic AST gene i...

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Section: Methodsmentioning

confidence: 99%

Effects of fenofibrate on plasma and hepatic transaminase activities and hepatic transaminase gene expression in rats

et al. 2009

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“…Serum samples were separated from whole blood and used to measure the myocardial enzyme type and level. Creatine kinase-MB (CK-MB) was measured by chemiluminescent immunoassay, 4 glutamate-oxaloacetate transaminase (m-GOT) was measured by the proteinase K method 5 and -hydroxybutyrate dehydrogenase (HBD) was measured by the RosalkiWilkinson method. 6 …”

Section: Measurement Of Myocardial Enzymesmentioning

confidence: 99%

Development and Evaluation of a New Canine Myocardial Infarction Model Using a Closed-Chest Injection of Thrombogenic Material

et al. 1999

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A new canine myocardial infarction model using thrombi induced by closed-chest injection of thrombin and autogenous blood with fibrinogen into coronary arteries was developed. Occlusive thrombi were formed in all treated animals. Occluded vessels did not spontaneously reperfuse 1 day after occlusion, but did so within 3 days. Infarction was confirmed by increased levels of creatine kinase-MB, glutamate-oxaloacetate transaminase and -hydroxybutyrate dehydrogenase. Additionally, the left ventricular ejection fraction (LVEF) decreased within 0.5 h after occlusion and had not improved 4 weeks later. After 1 week, extensive transmural anteroinferior myocardial infarction was observed and heart mass had increased. By 4 weeks after occlusion, pulmonary capillary wedge pressure and central venous pressure were increased, and oxygen pressure was decreased. Dropout of nuclei in cardiomyocytes and increased amount of collagen fiber were observed in myocardial infarct regions of hearts excised 4 weeks after occlusion. This canine model may be useful and convenient in evaluating treatment efficacy and the long-term outcome of acute myocardial infarction. (Jpn Circ J 1999; 63: 900 -905)

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“…Measurement methods for plasma mitochondriatype ALT or cytosol-type ALT have not been established (Rafter et al, 2012). Differences in the physicochemical properties between mitochondrial and cytosolic AST have been reported and the measurement methods of plasma mitochondria-type AST activity have been established (Watazu et al, 1993).…”

Section: Isozymes Of Transaminases and Their Intracellular Distributionmentioning

confidence: 99%

Specificity of transaminase activities in the prediction of drug-induced hepatotoxicity

2020

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The activities of the transaminases (aminotransferases) alanine aminotransferase and aspartate aminotransferase in the blood (serum or plasma) are widely used as sensitive markers of possible tissue damage and, in particular for liver toxicity. On the other hand, an increase in transaminase activities is not always accompanied by findings suggestive of hepatotoxicity. Transaminases are some of the key enzymes in the gluconeogenesis and glycolysis pathways and exist in many organs and tissues which have high activities of the gluconeogenesis and glycolysis. The activities of transaminases are altered not only in the liver but also in other organs by modification of gluconeogenesis by nutritional or hormonal factors and this phenomenon leads to alteration of transaminase activity in the blood. Drugs, which are considered to directly or secondarily modify gluconeogenesis through lowering blood glucose levels or activating lipid metabolism, such as α-glucosidase inhibitors and fibrates, slightly increase transaminase activities in the blood but there is little evidence that the phenomenon is related to drug-induced liver injury (DILI). This type of elevations can be called pharmacology-related elevation. The pharmacology-related elevation of transaminase activities sometimes makes it difficult to assess precisely the potential hepatotoxicity of new investigational drugs. Considering the characteristic of transaminases, concomitant use of new biomarkers more specific to hepatic injury is needed in the assessment of DILI both in non-clinical and clinical studies. In this review, we will discuss the specificity of transaminases to DILI and future perspectives for transaminases in the estimation of risk of DILI.

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Proteinase K inactivation of cytosolic aspartate aminotransferase isoenzyme for measurement of human serum mitochondrial aspartate aminotransferase

Cited by 3 publications

References 10 publications

Effects of fenofibrate on plasma and hepatic transaminase activities and hepatic transaminase gene expression in rats

Effects of fenofibrate on plasma and hepatic transaminase activities and hepatic transaminase gene expression in rats

Development and Evaluation of a New Canine Myocardial Infarction Model Using a Closed-Chest Injection of Thrombogenic Material

Specificity of transaminase activities in the prediction of drug-induced hepatotoxicity

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