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

Research output: Contribution to journalArticle

80 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)764-773
Number of pages10
JournalNeurobiology of Disease
Volume8
Issue number5
DOIs
StatePublished - Jan 1 2001

Fingerprint

Glial Cell Line-Derived Neurotrophic Factor
Aluminum
Mitochondria
Apoptosis
Rabbits
Caspase 3
Alzheimer Disease
Apoptosis Regulatory Proteins
In Situ Nick-End Labeling
DNA Fragmentation
Cytochromes c
Neuroglia
Endoplasmic Reticulum
DNA Damage
Up-Regulation
Therapeutics
Injections
Brain

Keywords

  • Aluminum
  • Bax
  • Bcl-2
  • Caspase-3
  • Cytochrome c
  • Endoplasmic reticulum
  • GDNF

ASJC Scopus subject areas

  • Neurology

Cite this

GDNF protects against aluminum-induced apoptosis in rabbits by upregulating Bcl-2 and Bcl-XL and inhibiting mitochondrial Bax translocation. / Ghribi, Othman; Herman, Mary M.; Forbes, Michael S.; DeWitt, David A.; Savory, John.

In: Neurobiology of Disease, Vol. 8, No. 5, 01.01.2001, p. 764-773.

Research output: Contribution to journalArticle

Ghribi, Othman ; Herman, Mary M. ; Forbes, Michael S. ; DeWitt, David A. ; Savory, John. / GDNF protects against aluminum-induced apoptosis in rabbits by upregulating Bcl-2 and Bcl-XL and inhibiting mitochondrial Bax translocation. In: Neurobiology of Disease. 2001 ; Vol. 8, No. 5. pp. 764-773.
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