Intrastriatal dopamine injection induces apoptosis through oxidation-involved activation of transcription factors AP-1 and NF-kappaB in rats

Author(s)

Y. Luo
A. Hattori
James R. Munoz, Nova Southeastern UniversityFollow
Z.H. Qin
G.S. Roth

Document Type

Article

Publication Date

1-1-1999

Publication Title

Molecular Pharmacology

Volume

56

Issue/Number

2

First Page

254

ISSN

0026-895X

Last Page

264

Abstract/Excerpt

ABSTRACT More and more evidence suggests that increases in dopamine (DA) in striata may participate in neurodegenerative processes during acute ischemia, hypoxia, and excitotoxicity. With a rat model of intrastriatal DA injection, we studied the molecular events involved in DA toxicity. Intrastriatal injections of DA in amounts from 1 to 2 micromol result in apoptotic cell death, as indicated by terminal deoxynucleotidyl transferase labeling of DNA strand breaks and Klenow polymerase-catalyzed [(32)P]deoxycytidine triphosphate-labeled DNA laddering. Injections of DA produce a strong and prolonged activated protein 1 (AP-1) activity that contains c-fos, c-jun, and phosphorylated c-jun protein. DA injections also stimulate the activity of nuclear factor-kappaB (NF-kappaB), an oxidative stress-responsive transcription factor. Injection of curcumin at a dose that selectively inhibits AP-1 activation without affecting NF-kappaB activity attenuates DNA laddering induced by DA. Preinjection with SN50, a specific permeable recombinant NF-kappaB translocation inhibitor peptide, reduces DA-induced NF-kappaB activation and apoptosis. Moreover, preinjection of the antioxidant GSH significantly inhibits both DA-induced activation of transcription factors AP-1 and NF-kappaB and subsequent apoptosis. Thus, our data suggest that DA-oxidative stress-induced apoptosis in vivo is mediated by activation of transcription factors AP-1 and NF-kappaB.

NSUWorks Citation

Luo, Y., Hattori, A., Munoz, J. R., Qin, Z., Roth, G. (1999). Intrastriatal dopamine injection induces apoptosis through oxidation-involved activation of transcription factors AP-1 and NF-kappaB in rats. Molecular Pharmacology, 56(2), 254-264.
Available at: https://nsuworks.nova.edu/cps_facarticles/1155