Scientists at Thomas Jefferson University, Farber Institute for Neurosciences release new data on leukemia genetics
2007 NOV 19 -- Research findings, 'A caspase-3-cleaved fragment of the glial glutamate transporter EAAT2 is sumoylated and targeted to promyelocytic leukemia nuclear bodies in mutant SOD1-linked amyotrophic lateral sclerosis,' are discussed in a new report. According to recent research from the United States, "EAAT2 (excitatory amino acid transporter 2) is a high affinity, Na+-dependent glutamate transporter of glial origin that is essential for the clearance of synaptically released glutamate and prevention of excitotoxicity. During the course of human amyotrophic lateral sclerosis (ALS) and in a transgenic mutant SOD1 mouse model of the disease, expression and activity of EAAT2 is remarkably reduced." "We previously showed that some of the mutant SOD1 proteins exposed to oxidative stress inhibit EAAT2 by triggering caspase-3 cleavage of EAAT2 at a single defined locus. This gives rise to two fragments that we termed truncated EAAT2 and COOH terminus of EAAT2 (CTE). In this study, we report that analysis of spinal cord homogenates prepared from mutant G93A-SOD1 mice reveals CTE to be of a higher molecular weight than expected because it is conjugated with SUMO-1. The sumoylated CTE fragment (CTE-SUMO-1) accumulates in the spinal cord of these mice as early as presymptomatic stage (70 days of age) and not in other central nervous system areas unaffected by the disease. The presence and accumulation of CTE-SUMO-1 is specific to ALS mice, since it does not occur in the R6/2 mouse model for Huntington disease. Furthermore, using an astroglial cell line, primary culture of astrocytes, and tissue samples from G93A-SOD1 mice, we show that CTE-SUMO-1 is targeted to promyelocytic leukemia nuclear bodies," wrote S.L. Gibb and colleagues, Thomas Jefferson University, Farber Institute for Neurosciences. The researchers concluded: "Since one of the proposed functions of promyelocytic leukemia nuclear bodies is regulation of gene transcription, we suggest a possible novel mechanism by which the glial glutamate transporter EAAT2 could contribute to the pathology of ALS." Gibb and colleagues published their study in the Journal of Biological Chemistry (A caspase-3-cleaved fragment of the glial glutamate transporter EAAT2 is sumoylated and targeted to promyelocytic leukemia nuclear bodies in mutant SOD1-linked amyotrophic lateral sclerosis. Journal of Biological Chemistry, 2007;282(44):32480-90). For additional information, contact S.L. Gibb, Farber Institute for Neurosciences, Weinberg Unit for ALS Research, Thomas Jefferson University, Philadelphia, Pennsylvania 19107 and Cecil B Day Laboratory for Neuromuscular Research, Massachusetts General Hospital, Charlestown 02129 USA.. Publisher contact information for the Journal of Biological Chemistry is: American Society Biochemistry Molecular Biology Inc., 9650 Rockville Pike, Bethesda, MD 20814-3996, USA. Keywords: United States, Leukemia Genetics, Amyotrophic Lateral Sclerosis, Biological Chemistry, Caspase, Enzyme Research, Hematology, Leukemia, Motor Neuron Disease, Neurology, Oncology. This article was prepared by Pain & Central Nervous System Week editors from staff and other reports. Copyright 2007, Pain & Central Nervous System Week via NewsRx.com.
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