Cyclic AMP and ethanol interact to control apoptosis and differentiation in hypothalamic β-endorphin neurons

A. De, N. I. Boyadjieva, M. Pastorcic, B. V. Reddy, D. K. Sarkar

Research output: Contribution to journalArticlepeer-review

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Abstract

In this study we have determined the role of cyclic AMP on the function and differentiation of β-endorphin (β-EP) neurons in rat fetal hypothalamic cell cultures. Addition of Bt2cAMP or the cAMP elevating agent, forskolin, in cultures, dose and time dependently increased β-endorphin secretion. The increased β-EP secretion after Bt2cAMP or forskolin treatment was associated with proopiomelanocortin gene expression, enhanced neurite growth, and increased neuronal viability. Determination of internucleosomal cleavage of DNA by agarose gel electrophoresis revealed that apoptosis occurred in hypothalamic neurons during the first 6-8 days in culture. Addition of Bt2cAMP during this developmental period inhibited DNA degradation in hypothalamic neurons. Furthermore, incubation with various doses of ethanol, which is known to reduce intracellular levels of Bt2cAMP, increased DNA degradation in these cells. Ethanol-induced DNA degradation was blocked by concomitant incubation with Bt2cAMP. Histochemical identification of apoptotic cells following ethanol and Bt2cAMP treatments further revealed that apoptosis occurred in β-EP neurons during the developmental period, and that ethanol increased and Bt2cAMP reduced apoptotic β-EP cell numbers. These results suggest that ethanol neurotoxicity on β-EP neurons during early neuronal differentiation involves an apoptotic process and that the cAMP signaling system plays an important role in controlling apoptosis and differentiation of the β-EP neuronal system.

Original languageEnglish (US)
Pages (from-to)26697-26704
Number of pages8
JournalJournal of Biological Chemistry
Volume269
Issue number43
StatePublished - 1994
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Biochemistry
  • Cell Biology

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