Stimulation of adrenal medullary cells in vivo and in vitro induces expression of c-fos proto-oncogene.
The nuclear proto-oncogene, c-fos, has been implicated in the coordinated regulation of gene expression during cell proliferation and differentiation. In this study, we have demonstrated the induction of the c-fos gene products in differentiated cells of the adrenal medulla by non-mitogenic signals. Activation of adrenal medullary cells in vivo by insulin-induced hypoglycemia, and in vitro by nicotine or angiotensin resulted in the rapid and transient elevation of c-fos mRNA levels. Induction of the c-fos mRNA by angiotensin and nicotine were accompanied by the appearance of the c-fos protein. The increase in c-fos protein occurred initially in the cytoplasm and, later, in the nucleus, and it was co-localized with tyrosine hydroxylase. Nuclear expression of the c-fos protein was also induced by veratridine, forskolin and the calcium ionophore A231287. The role of calcium in the regulation of the c-fos gene by angiotensin with nifedipine and inhibition of the effects of angiotensin with nifedipine and sphingosine, a protein kinase C inhibitor. Activation of the c-fos gene may play a role in the coordinated induction of genes involved in the long-term adaptation of adrenal medullary cells to increased functional demands.
Stachowiak
M K
MK
Laboratory of Molecular and Integrative Neuroscience, NIEHS, NIH, Research Triangle Park, North Carolina 27709.
Sar
M
M
Tuominen
R K
RK
Jiang
H K
HK
An
S
S
Iadarola
M J
MJ
Poisner
A M
AM
Hong
J S
JS
D000313:Adrenal Medulla / Q000378:metabolism*; D000809:Angiotensins / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000502:physiology; D002478:Cells, Cultured; D015870:Gene Expression; D008297:Male; D009538:Nicotine / Q000494:pharmacology; D011493:Protein Kinase C / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos; D011519:Proto-Oncogenes; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011916:Rats, Inbred F344
D000809:Angiotensins; D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D009538:Nicotine; D011493:Protein Kinase C; D002118:Calcium