Stress triggered changes in gene expression in adrenal medulla: Transcriptional responses to acute and chronic stress

被引:29
作者
Esther L. Sabban [1 ]
Xiaoping Liu [3 ]
Lidia Serova [1 ]
Volodia Gueorguiev [1 ]
Richard Kvetnansky [1 ]
机构
[1] Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla
[2] Institute of Experimental Endocrinology, Slovak Academy of Sciences, Bratislava
基金
美国国家卫生研究院;
关键词
Adrenal medulla; CREB; Fra-2; MAP kinase; Stress; Transcription factors;
D O I
10.1007/s10571-006-9069-1
中图分类号
学科分类号
摘要
1. Stress elicits activation of several transcription factors involved in the regulation of catecholamine biosynthetic enzyme gene expression depending on its duration or repetition. However, the dynamic of the conversion of transient transcriptional activation with acute stress to sustained changes in transcription in response to repeated exposure to stress in adrenomedullary catecholaminergic systems is not clear. 2. Here, we analyzed changes in levels of phospho-CREB (P-CREB), phospho-ERK1/2 (P-ERK1/2) and Fra-2 by Western Blot analysis in adrenal medulla of Sprague Dawley male rats exposed to single or repeated immobilization stress (IMO). For single stress, rats were immobilized for 5 min, 30 min, or 2 h and sacrificed immediately afterwards. In the repeated stress conditions, animals were immobilized for 2 h daily on each consecutive day prior to the final day (day 2 for 2 x IMO, day 6 for 6 x IMO) in which the rats were immobilized for a session lasting 5 min, 30 min or 2 h. There were two control groups, an absolute control (AC) not exposed to stress, and a handled control (HC) gently handled daily for 6 days. 3. Phosphorylation of CREB was rapid and elevated at the earliest time examined, even with single stress. However, with a second daily episode of stress the increase in P-CREB was observed for at least the entire duration of the stress. In contrast, phosphorylation of ERK1/2 was only significant after brief exposure to a single IMO. The elevation of Fra-2 protein level was slower, but was significant after 2 h of a single IMO. With repeated IMO, there were marked elevations of Fra-2 throughout the 2 h IMO, which were especially pronounced at the end of the immobilization. 4. The transient nature of the phosphorylation of CREB may be responsible for the short-lived induction of transcription of catecholamine biosynthetic enzymes after brief exposure to a single immobilization stress. The sustained phosphorylation of CREB throughout the repeated stress coupled with induction of Fra-2 may mediate the longer lasting responses to repeated stress. © 2006 Springer Science+Business Media, Inc.
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页码:845 / 856
页数:11
相关论文
共 46 条
[21]  
Lewis-Tuffin L.J., Quinn P.G., Chikaraishi D.M., Tyrosine hydroxylase transcription depends primarily on cAMP response element activity, regardless of the type of inducing stimulus, Molecular and Cellular Neuroscience, 25, 3, pp. 536-547, (2004)
[22]  
Liu X., Kvetnansky R., Serova L., Sollas A., Sabban E.L., Increased susceptibility to transcriptional changes with novel stressor in adrenal medulla of rats exposed to prolonged cold stress, Molecular Brain Research, 141, 1, pp. 19-29, (2005)
[23]  
McEwen B.S., Protective and damaging effects of stress mediators, N. Engl. J. Med., 338, 3, pp. 171-179, (1998)
[24]  
McMahon A., Kvetnansky R., Et al., Regulation of tyrosine hydroxylase and dopamine beta-hydroxylase mRNA levels in rat adrenals by a single and repeated immobilization stress, J. Neurochem., 58, 6, pp. 2124-2130, (1992)
[25]  
Montminy M.R., Bilezikjian L.M., Binding of a nuclear protein to the cyclic-AMP response element of the somatostatin gene, Nature, 328, 6126, pp. 175-178, (1987)
[26]  
Nankova B., Kvetnansky R., Mcmahon A., Viskupic E., Hiremagalur B., Frankle G., Fukuhara K., Kopin I.J., Sabban E.L., Induction of tyrosine hydroxylase gene expression by a nonneuronal nonpituitary-mediated mechanism in immobilization stress, Proceedings of the National Academy of Sciences of the United States of America, 91, 13, pp. 5937-5941, (1994)
[27]  
Nankova B.B., Rivkin M., Kelz M., Nestler E.J., Sabban E.L., Fos-related antigen 2: Potential mediator of the transcriptional activation in rat adrenal medulla evoked by repeated immobilization stress, Journal of Neuroscience, 20, 15, pp. 5647-5653, (2000)
[28]  
Nankova B.B., Sabban E.L., Multiple signalling pathways exist in the stress-triggered regulation of gene expression for catecholamine biosynthetic enzymes and several neuropeptides in the rat adrenal medulla, Acta Physiologica Scandinavica, 167, 1, pp. 1-9, (1999)
[29]  
Nankova B.B., Tank A.W., Sabban E.L., Transient or sustained transcriptional activation of the genes encoding rat adrenomedullary catecholamine biosynthetic enzymes by different durations of immobilization stress, Neuroscience, 94, 3, pp. 803-808, (1999)
[30]  
Osterhout C.A., Chikaraishi D.M., Tank A.W., Induction of tyrosine hydroxylase protein and a transgene containing tyrosine hydroxylase 5' flanking sequences by stress in mouse adrenal gland, Journal of Neurochemistry, 68, 3, pp. 1071-1077, (1997)