- 作者: Young-Tae Ro; Bo-Kwang Jang; Chan Young Shin; Eui U Park; Chul Geun Kim; Sung-Il Yang
- 作者服務機構: Department of Pharmacology, School of Medicine, Konkuk University, Seoul, Republic of Korea
- 中文摘要: --
- 英文摘要:
Background: Akt regulates various cellular processes, including cell growth, survival, and metabolism. Recently,
Akt’s role in neurite outgrowth has also emerged. We thus aimed to identify neuronal function-related genes that
are regulated by Akt.
Methods: We performed suppression subtractive hybridization on two previously established PC12 sublines, one of
which overexpresses the wild-type (WT) form and the other, the dominant-negative (DN) form of Akt. These
sublines respond differently to NGF’s neuronal differentiation effect.
Results: A variety of genes was identified and could be classified into several functional groups, one of which was
developmental processes. Two genes involved in neuronal differentiation and function were found in this group. v-
Maf musculoaponeurotic fibrosarcoma oncogene homolog K (MafK) induces the neuronal differentiation of PC12
cells and immature telencephalon neurons, and synaptotagmin I (SytI) is essential for neurotransmitter release.
Another gene, syntenin-1 (Syn-1) was also recognized in the same functional group into which MafK and SytI were
classified. Syn-1 has been reported to promote the formation of membrane varicosities in neurons. Quantitative
reverse transcription polymerase chain reaction analyses show that the transcript levels of these three genes were
lower in PC12 (WT-Akt) cells than in parental PC12 and PC12 (DN-Akt) cells. Furthermore, treatment of PC12 (WTAkt)
cells with an Akt inhibitor resulted in the increase of the expression of these genes and the improvement of
neurite outgrowth. These results indicate that dominant-negative or pharmacological inhibition of Akt increases the
expression of MafK, SytI, and Syn-1 genes. Using lentiviral shRNA to knock down endogenous Syn-1 expression, we
demonstrated that Syn-1 promotes an increase in the numbers of neurites and branches.
Conclusions: Taken together, these results indicate that Akt negatively regulates the expression of MafK, SytI, and
Syn-1 genes that all participate in regulating neuronal integrity in some way or another. - 中文關鍵字: --
- 英文關鍵字: --