Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.2.1.13 (glyceraldehyde-3-phosphate dehydrogenase)
 6,511 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Acrylamide is an important chemical used in the synthesis of polyacrylamides, which have a wide variety of industrial applications. The principal toxic effect of acrylamide, both in animals and in humans, is neurotoxicity. Peripheral nervous system effects are most prominent, but central nervous system effects have also been reported. Acrylamide is metabolized to the epoxide glycidamide, whose adducts to hemoglobin and to DNA have been identified in animals and humans. This metabolite may be involved in the reproductive and carcinogenic effects of acrylamide. In the present study we investigated whether glycidamide would exert neurotoxic effects similar to those caused by its parent compound. Male rats were injected i.p. with acrylamide (25 or 50 mg/kg) or glycidamide (50 or 100 mg/kg) daily for 8 days. Reduced weight gain was evident in animals exposed to glycidamide or to the higher dose of acrylamide. Both compounds induced lethargy and ataxia, but the posture of glycidamide-treated rats differed from that of animals treated with acrylamide. At the high doses, both compounds significantly affected rats' behavior in the rotarod test; on the other hand, only acrylamide was effective in the hindlimb splay test. Acrylamide inhibited activity of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in sciatic and tibial nerves, as well as in brain. Glycidamide inhibited GAPDH activity only in brain and activity of creatine kinase in both peripheral and central tissues. Acrylamide also caused profound urinary retention and distended bladders, while the effects of glycidamide were minimal. Morphological abnormalities were seen in sciatic nerves and dorsal root ganglion cells of rats treated with acrylamide (50 mg/kg x 12), but not in rats exposed to glycidamide (100 mg/kg x 11). These results indicate that the toxicities of acrylamide and glycidamide differ and suggest that acrylamide itself may be primarily responsible for its peripheral neurotoxicity.
 ...
PMID:Evaluation of the neurotoxicity of glycidamide, an epoxide metabolite of acrylamide: behavioral, neurochemical and morphological studies. 774 May 44

Doppel (PRND) is a paralogue of the mammalian prion (PRNP) gene. It is abundant in testis and, unlike PRNP, it is expressed at low levels in the adult central nervous system (CNS). Besides, doppel overexpression correlates with some prion-disease pathological features, such as ataxia and death of cerebellar neurons. Recently, ectopic expression of doppel was found in two different tumor types, specifically in glial and haematological cancers. In order to address clinical important issues, PRND mRNA expression was investigated in a panel of 111 astrocytoma tissue samples, histologically classified according to the World Health Organization (WHO) criteria (6 grade I pilocytic astrocytomas, 15 grade II low-grade astrocytomas, 26 grade III anaplastic astrocytomas and 64 grade IV glioblastoma multiforme). Real-time PRND gene expression profiling, after normalisation with GAPDH, revealed large differences between low (WHO I and II) and high grade (III and IV) of malignancy (P<0.001). Extensive differences in PRND gene expression were also found within each grade of malignancy, suggesting that PRND mRNA quantitation might be useful to distinguish astrocytoma subtypes, and important in disease stratification and in the assessment of specific treatment strategies.
 ...
PMID:Diagnostic value of PRND gene expression profiles in astrocytomas: relationship to tumor grades of malignancy. 1739 34