Adrenomedullin (AM) and proadrenomedullin N-terminal 20 peptide (PAMP)
are multi-functional peptides derived from the same precursor, proadrenomedullin.
We have studied the regulatory mechanism of expression of these peptides during
neuronal differentiation of rat pheochromocytoma PC12 cells by nerve growth factor
(NGF). The cellular levels of the peptides increased slightly, and then progressively
decreased below the control by NGF. Immunoreactive (ir)- AM in the medium was
transiently increased by NGF. Cytochemical staining showed that ir-AM and
ir-PAMP were abundantly present in cytoplasm in the undifferentiated cells, and were
decreased during culture with NGF. There was no preferential localization of ir-AM
or ir-PAMP in neurites in comparison with in cytoplasm in the differentiated cells.
Northern blot analysis showed that mRNA encoding these peptides, as detected as a
band of 1.6 kb, increased more than 3-fold at 1 hour after the addition of NGF and then
progressively decreased to 1/5 of the control during 72 hours. Degradation rate of the
mRNA was slowed by NGF even when mRNA level is decreased after 72 hours of NGF
treatment. The transcription rate of their gene increased transiently and then decreased
by the long-term treatment with NGF. These results demonstrate that expression of
AM and PAMP is regulated by NGF along with time-dependent differentiation: AM
gene transcription is transiently activated by NGF, whereas was suppressed during
neuronal differentiation of the cells.
リポジトリのご案内
Expression of Adrenomedullin and Proadrenomedullin N-Terminal 20 Peptide in PC12 Cells after Exposure to Nerve Growth Factor
Neuroscience 125(4) p.73-980,2004.pdf
(1.36MB)
