Intrastriatal dopamine injection induces apoptosis through oxidation-involved activation of transcription factors AP-1 and NF-kappaB in ratsMolecular Pharmacology
AbstractABSTRACT 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.
Citation InformationY. Luo, A. Hattori, James R. Munoz, Z.H. Qin, et al.. "Intrastriatal dopamine injection induces apoptosis through oxidation-involved activation of transcription factors AP-1 and NF-kappaB in rats" Molecular Pharmacology Vol. 56 Iss. 2 (1999) p. 254 - 264 ISSN: 0026-895X
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