Cerebral localization and regulation of the cell volume-sensitive serum- and glucocorticoid-dependent kinase SGK1

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.

Impaired Mast Cell Activation in Gene-Targeted Mice Lacking the Serum- and Glucocorticoid-Inducible Kinase SGK1

“…Thus, SGK1 blunts the Ag-induced activation of those channels largely by compromising Ca 2ϩ entry with only little or no direct effect on the Ca 2ϩ -activated K ϩ channels. In other cells, SGK1 has been shown to activate a wide variety of different K ϩ channels (40,55,(57)(58)(59)(60)(61)(62)(63)(64). The present study does not rule out Ca 2ϩ -independent effects of SGK1 on K ϩ channels and other functions of mast cells.…”

Dietary Salt Regulates Renal SGK1 Abundance

“…28 Oxidant stress cannot be excluded as an inducer of SGK1 in hypertension. 29 Transcription of SGK1 is markedly upregulated by osmotic and isotonic cell shrinkage 30,31 ; however, osmotic changes in salt-adaptation and salt-sensitive hypertension in the kidney remain to be fully clarified.…”

Memory Reconsolidation Engages Only a Subset of Immediate-Early Genes Induced during Consolidation

“…SGK3 is therefore a suitable marker to study contextshock memory consolidation. SGK3 has been shown to activate the Shaker-related K v 1 potassium channels (Warntges et al, 2002;Gamper et al, 2002a,b). It is therefore conceivable that SGK3 regulates the activity of voltage-gated potassium channels and hence neuronal excitability, a putative L&M mechanism (Giese et al, 2001).…”