사람 Neuroblastoma SH-SY5Y 세포주에서 Opiate 내성에 의한 c-myc 유전자 표현

The c-myc Expression on the Opioid Tolerance in Human Neuroblastoma SH-SY5Y Cells

<P> The mechanisms underlying opiate tolerance and dependence are not fully understood. We used human neuroblastoma SH-SY5Y cells as a model system for studying effects of morphine tolerance and withdrawal on <I>c-myc</I> induction and cAMP levels. It has been reported that regulation of <I>c-fos</I> by acute and chronic morphine withdrawal is mediated through alterations in CREB transcription factor. <P> In this study, we examined the effects of morphine tolerance on <I>c-myc</I> expression and cAMP concentrations. The activation of opiate receptors by an acute morphine administration resulted in an increase in <I>c-myc</I> mRNA and a decrease in cAMP concentrations in a dose-dependent manner (5, 10, 15, and 20 &#12557;M). On the other hand, the chronic treatment of morphine (10 &#12557;M for six days) did not induce the elevated expression of <I>c-myc</I> mRNA. The <I>c-myc</I> expression was slightly inhibited in comparison with that of the acute morphine response. However, cAMP concentrations were increased with regard to morphine withdrawal response. <P> These results suggest that the alterations in <I>c-myc </I>expression might imply a significant opiate regulation relating to morphine tolerance. This observation differs from increased expression of <I>c-fos via</I> regulation of cAMP pathway.