Cerebral localization and regulation of the cell volume-sensitive serum- and glucocorticoid-dependent kinase SGK1 (original) (raw)

Abstract

The serum- and glucocorticoid-dependent kinase SGK1 is regulated by alterations of cell volume, whereby cell shrinkage increases and cell swelling decreases the transcription, expression and activity of SGK1. The kinase is expressed in all human tissues studied including the brain. The present study was performed to localize the sites of SGK1 transcription in the brain, to elucidate the influence of the hydration status on SGK1 transcription and to explore the functional significance of altered SGK1 expression. Northern blot analysis of human brain showed SGK1 to be expressed in all cerebral structures examined: amygdala, caudate nucleus, corpus callosum, hippocampus, substantia nigra, subthalamic nucleus and thalamus. In situ hybridization and immunohistochemistry in the rat revealed increased expression of SGK1 in neurons of the hippocampal area CA3 after dehydration, compared with similar slices from brains of euvolaemic rats. Additionally, several oligodendrocytes, a few microglial cells, but no astrocytes, were positive for SGK1. The abundance of SGK1 mRNA in the temporal lobe, including hippocampus, was increased by dehydration and SGK1 transcription in neuroblastoma cells was stimulated by an increase of extracellular osmolarity. Co-expression studies in Xenopus laevis oocytes revealed that SGK1 markedly increased the activity of the neuronal K+ channel Kv1.3. As activation of K+ channels modifies excitation of neuronal cells, SGK1 may participate in the regulation of neuronal excitability.

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Authors and Affiliations

1. Physiologisches Institut der Universität Tübingen, Gmelinstrassse 5, 72076 Tübingen,, Germany
   S. Wärntges, B. Friedrich, G. Henke, C. Duranton, P. Lang, S. Waldegger, S. Bröer & F. Lang
2. Department of Brain Research, University of Tübingen, Germany
   R. Meyermann
3. Zentrum für Molekulare Neurobiologie, Universität Hamburg, Germany
   D. Kuhl
4. Department of Physiology, University of Münster, Germany
   E. Speckmann
5. Department of Anatomy, University of Heidelberg, Germany
   N. Obermüller & R. Witzgall
6. Department of Anatomy, University of Tübingen, Germany
   A. Mack & H. Wagner
7. Department of Cellular and Molecular Physiology, Yale University, New Haven, Conn. USA, USA
   C. A. Wagner

Authors

1. S. Wärntges
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2. B. Friedrich
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3. G. Henke
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4. C. Duranton
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5. P. Lang
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6. S. Waldegger
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7. R. Meyermann
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8. D. Kuhl
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9. E. Speckmann
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10. N. Obermüller
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11. R. Witzgall
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12. A. Mack
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13. H. Wagner
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14. C. A. Wagner
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15. S. Bröer
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16. F. Lang
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Wärntges, S., Friedrich, B., Henke, G. et al. Cerebral localization and regulation of the cell volume-sensitive serum- and glucocorticoid-dependent kinase SGK1.Pflügers Arch - Eur J Physiol 443, 617–624 (2002). https://doi.org/10.1007/s00424-001-0737-1

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• Received: 09 May 2001
• Revised: 21 August 2001
• Accepted: 13 September 2001
• Published: 09 November 2001
• Issue Date: February 2002
• DOI: https://doi.org/10.1007/s00424-001-0737-1