Skip to main content
Journal cover image

Differential regulation of c-jun and CREB by acrolein and 4-hydroxynonenal.

Publication ,  Journal Article
Pugazhenthi, S; Phansalkar, K; Audesirk, G; West, A; Cabell, L
Published in: Free Radic Biol Med
January 1, 2006

In Alzheimer's disease (AD), oxidative stress-induced lipid peroxidation leads to accumulation of unsaturated aldehydes including acrolein and 4-hydroxynonenal (4HNE) in brain. In this study, we examined the effects of these lipid peroxidation products on apoptotic pathways in cultured neurons. Acrolein and 4HNE increased the levels of active phosphorylated forms of c-jun and CREB, the transcription factors that promote apoptosis and cell survival, respectively. However, they decreased the activity of CREB-dependent BDNF promoter while they increased the activity of promoters responsive to c-jun. We hypothesized that this differential regulation could be due to competition between proapoptotic c-jun and cytoprotective CREB for CBP (CREB-binding protein), a coactivator shared by several transcription factors. In support of this hypothesis, we demonstrate that the decrease of BDNF promoter activity by acrolein and 4HNE could be restored (i) by cotransfection with CBP, (ii) by cotransfection with VP 16-CREB, a constitutively active form of CREB that does not depend on CBP for its activation, or (iii) by inhibiting JNK-mediated c-jun activation. Finally, adenoviral transduction of hippocampal neurons with VP 16-CREB resulted in significant reduction in caspase-3 activation by acrolein and 4HNE. These observations suggest that lipid peroxidation-induced differential regulation of CREB and c-jun might play a role in neurodegeneration in AD.

Duke Scholars

Published In

Free Radic Biol Med

DOI

ISSN

0891-5849

Publication Date

January 1, 2006

Volume

40

Issue

1

Start / End Page

21 / 34

Location

United States

Related Subject Headings

  • Rats, Sprague-Dawley
  • Rats
  • Proto-Oncogene Proteins c-jun
  • Promoter Regions, Genetic
  • Pregnancy
  • Phosphorylation
  • Neurons
  • Neuroblastoma
  • Lipid Peroxidation
  • Humans
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Pugazhenthi, S., Phansalkar, K., Audesirk, G., West, A., & Cabell, L. (2006). Differential regulation of c-jun and CREB by acrolein and 4-hydroxynonenal. Free Radic Biol Med, 40(1), 21–34. https://doi.org/10.1016/j.freeradbiomed.2005.08.023
Pugazhenthi, Subbiah, Ketaki Phansalkar, Gerald Audesirk, Anne West, and Leigh Cabell. “Differential regulation of c-jun and CREB by acrolein and 4-hydroxynonenal.Free Radic Biol Med 40, no. 1 (January 1, 2006): 21–34. https://doi.org/10.1016/j.freeradbiomed.2005.08.023.
Pugazhenthi S, Phansalkar K, Audesirk G, West A, Cabell L. Differential regulation of c-jun and CREB by acrolein and 4-hydroxynonenal. Free Radic Biol Med. 2006 Jan 1;40(1):21–34.
Pugazhenthi, Subbiah, et al. “Differential regulation of c-jun and CREB by acrolein and 4-hydroxynonenal.Free Radic Biol Med, vol. 40, no. 1, Jan. 2006, pp. 21–34. Pubmed, doi:10.1016/j.freeradbiomed.2005.08.023.
Pugazhenthi S, Phansalkar K, Audesirk G, West A, Cabell L. Differential regulation of c-jun and CREB by acrolein and 4-hydroxynonenal. Free Radic Biol Med. 2006 Jan 1;40(1):21–34.
Journal cover image

Published In

Free Radic Biol Med

DOI

ISSN

0891-5849

Publication Date

January 1, 2006

Volume

40

Issue

1

Start / End Page

21 / 34

Location

United States

Related Subject Headings

  • Rats, Sprague-Dawley
  • Rats
  • Proto-Oncogene Proteins c-jun
  • Promoter Regions, Genetic
  • Pregnancy
  • Phosphorylation
  • Neurons
  • Neuroblastoma
  • Lipid Peroxidation
  • Humans