GDNF Protects against Aluminum-Induced Apoptosis in Rabbits by Upregulating Bcl-2 and Bcl-XL and Inhibiting Mitochondrial Bax Translocation

Othman Ghribi; Mary M. Herman; Michael S. Forbes; David A. DeWitt; John Savory

Neurobiology of Disease (Oct 2001)

GDNF Protects against Aluminum-Induced Apoptosis in Rabbits by Upregulating Bcl-2 and Bcl-XL and Inhibiting Mitochondrial Bax Translocation

Othman Ghribi,
Mary M. Herman,
Michael S. Forbes,
David A. DeWitt,
John Savory

Affiliations

Othman Ghribi: Departments of Pathology, University of Virginia, Charlottesville, Virginia, 22908; Departments of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, Virginia, 22908; IRP, NIMH, NIH, Bethesda, Maryland, 20892; Department of Biology and Chemistry, Liberty University, Lynchburg, Virginia, 24506
Mary M. Herman: Departments of Pathology, University of Virginia, Charlottesville, Virginia, 22908; Departments of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, Virginia, 22908; IRP, NIMH, NIH, Bethesda, Maryland, 20892; Department of Biology and Chemistry, Liberty University, Lynchburg, Virginia, 24506
Michael S. Forbes: Departments of Pathology, University of Virginia, Charlottesville, Virginia, 22908; Departments of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, Virginia, 22908; IRP, NIMH, NIH, Bethesda, Maryland, 20892; Department of Biology and Chemistry, Liberty University, Lynchburg, Virginia, 24506
David A. DeWitt: Departments of Pathology, University of Virginia, Charlottesville, Virginia, 22908; Departments of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, Virginia, 22908; IRP, NIMH, NIH, Bethesda, Maryland, 20892; Department of Biology and Chemistry, Liberty University, Lynchburg, Virginia, 24506
John Savory: Departments of Pathology, University of Virginia, Charlottesville, Virginia, 22908; Departments of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, Virginia, 22908; IRP, NIMH, NIH, Bethesda, Maryland, 20892; Department of Biology and Chemistry, Liberty University, Lynchburg, Virginia, 24506

Journal volume & issue: Vol. 8, no. 5
pp. 764 – 773

Abstract

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Direct (intracisternal) injection of aluminum complexes into rabbit brain results in a number of similarities with the neuropathological and biochemical changes observed in Alzheimer's disease and provides the opportunity to assess early events in neurodegeneration. This mode of administration induces cytochrome c release from mitochondria, a decrease in Bcl-2 in both mitochondria and endoplasmic reticulum, Bax translocation into mitochondria, activation of caspase-3, and DNA fragmentation. Coadministration of glial cell neuronal-derived factor (GDNF) inhibits these Bcl-2 and Bax changes, upregulates Bcl-XL, and abolishes the caspase-3 activity. Furthermore, treatment with GDNF dramatically inhibits apoptosis, as assessed by the TUNEL technique for detecting DNA damage. Treatment with GDNF may represent a therapeutic strategy to reverse the neuronal death associated with Alzheimer's disease and may exert its effect on apoptosis-regulatory proteins.

Published in Neurobiology of Disease

ISSN: 0969-9961 (Print); 1095-953X (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Neurosciences. Biological psychiatry. Neuropsychiatry
Website: https://www.journals.elsevier.com/neurobiology-of-disease

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