Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002736 (amyotrophic lateral sclerosis)
 19,048 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Injury to motor neurons associated with mutant Cu,Zn-superoxide dismutase (SOD1)-related familial amyotrophic lateral sclerosis (FALS) results from a toxic gain-of-function of the enzyme. The mechanisms by which alterations to SOD1 elicit neuronal death remain uncertain despite intensive research effort. Analysis of the cellular proteins that are differentially expressed in the presence of mutant SOD1 represents a novel approach to investigate further this toxic gain-of-function. By using the motor neuron-like cell line NSC34 stably transfected with wild-type, G93A, or G37R mutant human SOD1, we investigated the effects of mutant human SOD1 on protein expression using proteomic approaches. Seven up-regulated proteins were identified as argininosuccinate synthase, argininosuccinate lyase, neuronal nitric-oxide synthase, RNA-binding motif protein 3, peroxiredoxin I, proteasome subunit beta 5 (X), and glutathione S-transferase (GST) Alpha 2. Seven down-regulated proteins were identified as GST Mu 1, GST Mu 2, GST Mu 5, a hypothetical GST Mu, GST Pi B, leukotriene B(4) 12-hydroxydehydrogenase, and proteasome subunit beta5i (LMP7). GST assays demonstrated a significant reduction in the total GST activity of cells expressing mutant human SOD1. Proteasome assays demonstrated significant reductions in chymotrypsin-like, trypsin-like, and post-glutamylhydrolase proteasome activities. Laser capture microdissection of spinal cord motor neurons from human FALS cases, in conjunction with reverse transcriptase-PCR, demonstrated decreased levels of mRNA encoding GST Mu 1, leukotriene B(4) 12-hydroxydehydrogenase, and LMP7. These combined approaches provide further evidence for involvement of alterations in antioxidant defenses, proteasome function, and nitric oxide metabolism in the pathophysiology of FALS.
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PMID:Analysis of the cytosolic proteome in a cell culture model of familial amyotrophic lateral sclerosis reveals alterations to the proteasome, antioxidant defenses, and nitric oxide synthetic pathways. 1247 80

The objectives of this research were to establish an automatic analysis method for the determination of serum argininosuccinate lyase (ASL) and to investigate the value of serum ASL test in the diagnosis of various liver disorders. According to the chemical reaction catalyzed by ASL, an enzyme-coupled reaction system was designed, and a methodology evaluation of this method was performed. A total of 291 patients with various liver diseases, 247 patients with nonliver disease and 32 healthy controls, were recruited, their serum levels of ASL and traditional hepatopathy markers, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyltransferase (GGT), lactate dehydrogenase (LDH), alkaline phosphatase (ALP), and total bilirubin (TBil), were all determined, and their diagnostic values in liver diseases were analyzed and compared. Liver biopsy and the score of histopathological inflammation grading were performed in 31 patients with hepatopathy to explore the correlation between serum ASL level and hepatic histopathological change. A continuous monitoring assay method of serum ASL activity was established, which could be performed with automatic biochemistry analyzer. Methodological evaluation exhibited that the precision of this method was good indicated by the 4.0% intraassay coefficient of variation (CV), and 5.9% interassay CV. The mean recovery was 100.5%, linear range was from 0 to 167.7 U/L, and the lowest detection limit was approximately 0 U/L. All of the tested hepatopathy markers listed above were significantly increased in the liver disease group. However, levels of traditional markers of hepatopathy were all significantly increased at different degrees (all P<0.001) in patients with nonliver diseases; in contrast, there were no significantly increased ASL levels in all non-hepatopathy groups (P=0.335). The receiver operating characteristic (ROC) curve showed that the sensitivity and specificity of ASL were 100% and 91.1% (cutoff value=8 U/L), respectively, in the assessment of liver diseases. In contrast, ALT levels were 97.6% and 24.7%, and AST levels were 83.8% and 28.3% (both cutoff values=40.0 U/L), respectively. A positive correlation (r=0.417, P=0.019) was observed between serum ASL levels (86.9+/-26.5) and scores of histopathological inflammation grading (SHIG) (9.83+/-3.36). The sensitivity and specificity of ALS is much higher than that of ALT and AST for the diagnosis of liver diseases. ASL may be a more valuable marker for estimating hepatopathy.
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PMID:Study of serum argininosuccinate lyase determination for diagnosis of liver diseases. 1848 60