Sgk1, a cell survival response in neurodegenerative diseases

Schoenebeck, Bodo; Bader, Verian; Zhu, Xin-Ran; Schmitz, Beate; Lübbert, Hermann; Stichel, Christine C.

doi:10.1016/j.mcn.2005.07.017

Cited by 67 publications

(65 citation statements)

References 59 publications

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“…This gene was at the top of the list of genes regulated, both, by dexamethasone in cultured astrocytes and by morphine in the mouse striatum. Alterations in the level of Sgk1 transcript or protein have been previously observed in the CNS in various models of stress (Koya et al, 2005;Murata et al, 2005;Yuen et al, 2010), after exposure to dexamethasone (Sato et al, 2008;David et al, 2005;van Gemert et al, 2006), drugs of abuse (Piechota et al, 2010b) and antidepressants (Conti et al, 2007), as well as in animal models of memory formation (von Hertzen and Giese, 2005) and neurodegeneration (Iwata et al, 2004;Rangone et al, 2004;Schoenebeck et al, 2005). Our results show that GR-responsive isoforms of Sgk1 are confined to astrocytes.…”

Section: Regulation Of Sgk1 Expression In Neural Cellssupporting

confidence: 73%

Astrocytes are a neural target of morphine action via glucocorticoid receptor‐dependent signaling

Ślęzak

Korostyński

Gieryk

et al. 2013

Glia

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Chronic opioid use leads to the structural reorganization of neuronal networks, involving genetic reprogramming in neurons and glial cells. Our previous in vivo studies have revealed that a significant fraction of the morphine-induced alterations to the striatal transcriptome included glucocorticoid (GC) receptor (GR)-dependent genes. Additional analyses suggested glial cells to be the locus of these changes. In the current study, we aimed to differentiate the direct transcriptional effects of morphine and a GR agonist on primary striatal neurons and astrocytes. Whole-genome transcriptional profiling revealed that while morphine had no significant effect on gene expression in both cell types, dexamethasone significantly altered the transcriptional profile in astrocytes but not neurons. We obtained a complete dataset of genes undergoing the regulation, which includes genes related to glucose metabolism (Pdk4), circadian activity (Per1) and cell differentiation (Sox2). There was also an overlap between morphine-induced transcripts in striatum and GR-dependent transcripts in cultured astrocytes. We further analyzed the regulation of expression of one gene belonging to both groups, serum and GC regulated kinase 1 (Sgk1). We identified two transcriptional variants of Sgk1 that displayed selective GR-dependent upregulation in cultured astrocytes but not neurons. Moreover, these variants were the only two that were found to be upregulated in vivo by morphine in a GR-dependent fashion. Our data suggest that the morphine-induced, GR-dependent component of transcriptome alterations in the striatum is confined to astrocytes. Identification of this mechanism opens new directions for research on the role of astrocytes in the central effects of opioids. V V C 2013 Wiley Periodicals, Inc.

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Section: Regulation Of Sgk1 Expression In Neural Cellssupporting

confidence: 73%

Astrocytes are a neural target of morphine action via glucocorticoid receptor‐dependent signaling

Ślęzak

Korostyński

Gieryk

et al. 2013

Glia

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“…Many genes are regulated by corticosterone (e.g., SGK1, CEBPB, and NFKBIA), some of which were also predicted as downstream of cortisol in this study. For instance, SGK1, whose expression is directly affected by corticosterone with an emphasis on metabolism, is involved in cellular functions such as glucose transport (Jeyaraj et al 2007), regulation of voltage-gated channels (Boehmer et al 2008), and apoptotic processes (Schoenebeck et al 2005). Other molecules in our study that were regulated by cortisol with an emphasis effect on lipid or transport metabolism were ACSL1, APOC3, PCTP, SREBF2, INSIG1, LIPG, NFKBIA, and ITGB3.…”

Section: Biological Function and Molecular Pathways Correlated With Cmentioning

confidence: 70%

Elucidating Molecular Networks That Either Affect or Respond to Plasma Cortisol Concentration in Target Tissues of Liver and Muscle

Ponsuksili

Muráni

et al. 2012

Genetics

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Cortisol is a steroid hormone with important roles in regulating immune and metabolic functions and organismal responses to external stimuli are mediated by the glucocorticoid system. Dysregulation of the afferent and efferent axis of glucocorticoid signaling have adverse effects on growth, health status, and well-being. Glucocorticoid secretion and signaling show large interindividual variation that has a considerable genetic component; however, little is known about the underlying genetic variants. Here, we used trait-correlated expression analysis, screening for expression quantitative trait loci (eQTL), genome-wide association (GWA) studies, and causality modeling to identify candidate genes in porcine liver and muscle that affect or respond to plasma cortisol levels. Through trait-correlated expression, we characterized transcript activities in many biological functions in liver and muscle. Candidates from the list of trait-correlated expressed genes were narrowed using only those genes with an eQTL, and these were further prioritized by determining whether their expression was predicted to be related to variation in plasma cortisol levels. Using network edge orienting (NEO), a causality modeling algorithm, 26 of 990 candidates in liver were predicted to affect and 70 to respond to plasma cortisol levels. Of 593 candidates in muscle that were correlated with cortisol levels and were regulated by eQTL, 2 and 25 were predicted as effective and responsive, respectively, to plasma cortisol levels. Comprehensive data integration has helped to elucidate the complex molecular networks contributing to cortisol levels and thus its subsequent metabolic effects. The discrimination of up-and downstream effects of transcripts affecting or responding to plasma cortisol concentrations improves the understanding of the biology of complex traits related to growth, health, and well-being. C ORTISOL, a steroid hormone released in response to stress and a low level of blood glucocorticoids, acts to increase blood sugar through gluconeogenesis; suppress the immune system; and aid in fat, protein, and carbohydrate metabolism. Produced in the adrenal cortex under the control of the hypothalamic-pituitary-adrenal axis and the sympatho-adrenomedullar (SAM) system, cortisol is most important during times of stress, when it modulates many of the acute responses to illness and "resets" metabolism in favor of providing substrates for oxidative metabolism (Andrews and Walker 1999). Stress factors can unbalance metabolic homeostasis, directing the demand for nutrients and energy for essential physiological processes away from growth (Heetkamp et al. 1995). Individual cortisol concentration is variable and depends on sensitivity to stress, which is highly genetically determined (e.g., heritability estimates of 0.40-0.70 in pigs) (Geverink et al. 2002; Kadarmideen and Janss 2009). According to the function of cortisol in the maintenance of basal and stress-related homeostasis the adrenocortical steroidogenesis is sensitive to exo...

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“…91,92 Sgk1 is similar in primary structure to protein kinase B (PKB), protein kinase C (PKC) and protein kinase A (PKA). In the brain or in brain cells, transcription of Sgk1 is increased in several animal models of Parkinson's disease 93 and a transgenic model of amyotrophic lateral sclerosis (ALS), following brain injury 94 and after transient global cerebral ischemia. 95 Increased expression of Sgk1 has been observed in the Hippo of fast-learning rats as compared with slow-learning rats.…”

Section: Number Of Transcripts Affected By Single and Multiple Treatmmentioning

confidence: 99%

Region-specific transcriptional changes following the three antidepressant treatments electro convulsive therapy, sleep deprivation and fluoxetine

et al. 2006

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The significant proportion of depressed patients that are resistant to monoaminergic drug therapy and the slow onset of therapeutic effects of the selective serotonin reuptake inhibitors (SSRIs)/serotonin/noradrenaline reuptake inhibitors (SNRIs) are two major reasons for the sustained search for new antidepressants. In an attempt to identify common underlying mechanisms for fast-and slow-acting antidepressant modalities, we have examined the transcriptional changes in seven different brain regions of the rat brain induced by three clinically effective antidepressant treatments: electro convulsive therapy (ECT), sleep deprivation (SD), and fluoxetine (FLX), the most commonly used slow-onset antidepressant. Each of these antidepressant treatments was applied with the same regimen known to have clinical efficacy: 2 days of ECT (four sessions per day), 24 h of SD, and 14 days of daily treatment of FLX, respectively. Transcriptional changes were evaluated on RNA extracted from seven different brain regions using the Affymetrix rat genome microarray 230 2.0. The gene chip data were validated using in situ hybridization or autoradiography for selected genes. The major findings of the study are:1. The transcriptional changes induced by SD, ECT and SSRI display a regionally specific distribution distinct to each treatment. 2. The fast-onset, short-lived antidepressant treatments ECT and SD evoked transcriptional changes primarily in the catecholaminergic system, whereas the slow-onset antidepressant FLX treatment evoked transcriptional changes in the serotonergic system. 3. ECT and SD affect in a similar manner the same brain regions, primarily the locus coeruleus, whereas the effects of FLX were primarily in the dorsal raphe and hypothalamus, suggesting that both different regions and pathways account for fast onset but short lasting effects as compared to slow-onset but long-lasting effects. However, the similarity between effects of ECT and SD is somewhat confounded by the fact that the two treatments appear to regulate a number of transcripts in an opposite manner. 4. Multiple transcripts (e.g. brain-derived neurotrophic factor (BDNF), serum/glucocorticoidregulated kinase (Sgk1)), whose level was reported to be affected by antidepressants or behavioral manipulations, were also found to be regulated by the treatments used in the present study. Several novel findings of transcriptional regulation upon one, two or all three treatments were made, for the latter we highlight homer, erg2, HSP27, the proto oncogene ret, sulfotransferase family 1A (Sult1a1), glycerol 3-phosphate dehydrogenase (GPD3), the orphan receptor G protein-coupled receptor 88 (GPR88) and a large number of expressed sequence tags (ESTs). 5. Transcripts encoding proteins involved in synaptic plasticity in the hippocampus were strongly affected by ECT and SD, but not by FLX.The novel transcripts, concomitantly regulated by several antidepressant treatments, may represent novel targets for fast onset, long-duration antidepressants.

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Sgk1, a cell survival response in neurodegenerative diseases

Cited by 67 publications

References 59 publications

Astrocytes are a neural target of morphine action via glucocorticoid receptor‐dependent signaling

Astrocytes are a neural target of morphine action via glucocorticoid receptor‐dependent signaling

Elucidating Molecular Networks That Either Affect or Respond to Plasma Cortisol Concentration in Target Tissues of Liver and Muscle

Region-specific transcriptional changes following the three antidepressant treatments electro convulsive therapy, sleep deprivation and fluoxetine

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