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

Author(s)

David A. Dewitt, Liberty UniversityFollow
Othman Ghribi
Mary M. Herman
Michael S. Forbes
John Savory

Publication Date

2001

Document Type

Article

Comments

Published in Neurobiology of Disease 8, 764–773 (2001).

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.

Recommended Citation

Dewitt, David A.; Ghribi, Othman; Herman, Mary M.; Forbes, Michael S.; and Savory, John, "GDNF Protects against Aluminum-Induced Apoptosis in Rabbits by Upregulating Bcl-2 and Bcl-XL and Inhibiting Mitochondrial Bax Translocation" (2001). Faculty Publications and Presentations. 8.
https://digitalcommons.liberty.edu/bio_chem_fac_pubs/8