Localization of the Glucocorticoid Receptor in Rat Brain Mitochondria

Moutsatsou, Paraskevi; Psarra, Anna‐Maria G.; Tsiapara, Anna; Paraskevakou, Helen; Davaris, P; Sékeris, Constantin E.

doi:10.1006/abbi.2000.2162

Cited by 102 publications

(67 citation statements)

References 42 publications

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“…Many earlier studies have described a range of unidentified bands in this size range in a number of human cell lines and non-brain rodent tissues. 9,66,67 If the 67-kDa isoform arises from an uncharacterized translation start site, this variant may be missing a component of the AF1 transactivation domain, potentially affecting its ability to activate target gene transcription. Alternatively, of the other characterized GRa isoforms (including GR-A, GRb, Dynamic changes in GR across human cortical development D Sinclair et al GR-P, GRg and GRD313-338), only GR-A is truncated but retains exon 9a, which contains the epitope targeted by the anti-GRa antibody in this study.…”

Section: Discussionmentioning

confidence: 99%

Dynamic molecular and anatomical changes in the glucocorticoid receptor in human cortical development

et al. 2010

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The glucocorticoid receptor (GR) has a critical role in determining the brain's capacity to respond to stress, and has been implicated in the pathogenesis of psychiatric illness. We hypothesized that key changes in cortical GR occur during adolescence and young adulthood, at a time when individuals are at increased risk of developing schizophrenia, bipolar disorder and major depression. We investigated the mRNA and protein expression of GR in the dorsolateral prefrontal cortex across seven developmental time points from infancy to adulthood. GR mRNA expression, determined by microarray and quantitative real-time PCR, was lowest in neonates and peaked around young adulthood. Western blotting revealed two dynamic patterns of GRa protein expression across the lifespan, with N-terminal variants displaying differing unique patterns of abundance. GRa-A and a 67-kDa GRa isoform mirrored mRNA trends and peaked in toddlers and late in adolescence, whereas a 40-kDa isoform, very likely a GRa-D variant, peaked in neonates and decreased across the lifespan. GRa protein was localized to pyramidal neurons throughout life and most strikingly in young adulthood, but to white matter astrocytes only in neonates and infants ( < 130 days). These results suggest that the neonatal and late adolescent periods represent critical windows of stress pathway development, and highlight the importance of white matter astrocytes and pyramidal neurons, respectively, at these stages of cortical development. Evidence of dynamic patterns of GR isoform expression and cellular localization across development strengthens the hypothesis that windows of vulnerability to stress exist across human cortical development.

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Section: Discussionmentioning

confidence: 99%

Dynamic molecular and anatomical changes in the glucocorticoid receptor in human cortical development

et al. 2010

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“…Specifically, GR was found in rat liver mitochondria of adrenalectomized animals, 15 min after dexamethasone administration, whereas in noninduced animals the mitochondria showed only traces of the receptor (45). GR was detected in mitochondria of HeLa cells (46), in cytoplasmic and synaptosomal mitochondria of rat brain (47), in mitochondria of Mueller glia cells of the Salamander retina (48) and of rat C6 glioma cells (49). GR was also located in HepG2 hepatocarcinoma and SaOS-2 osteosarcoma cell lines (42).…”

Section: The Detection Of Steroid and Thyroid Receptors In Mitochondriamentioning

confidence: 99%

“…The purification of receptor proteins and the availability of respective antibodies permitted the application of immune techniques, that is Western blotting, immunofluorescence, confocal and immunogold electron microscopy, for the identification of glucocorticoid (GR), estrogen (ER), androgen (AR), and thyroid hormone (TR) receptors in mitochondria (Fig. 2, Table 1) (37,(42)(43)(44)(45)(46)(47)(48)(49)(50)(51)(52)(53)(54)(55)(56)(57)(58)(59)(60)(66)(67)(68)(69).…”

Section: The Detection Of Steroid and Thyroid Receptors In Mitochondriamentioning

confidence: 99%

Steroid and thyroid hormone receptors in mitochondria

2008

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SummaryReceptors for glucocorticoids, estrogens, androgens, and thyroid hormones have been detected in mitochondria of various cell types by Western blotting, immunofluorescence labeling, confocal microscopy, and immunogold electron microscopy. A role of these receptors in mitochondrial transcription, OXPHOS biosynthesis, and apoptosis is now being revealed. Steroid and thyroid hormones regulate energy production, inducing nuclear and mitochondrial OXPHOS genes by way of cognate receptors. In addition to the action of the nuclearly localized receptors on nuclear OXPHOS gene transcription, a parallel direct action of the mitochondrially localized receptors on mitochondrial transcription has been demonstrated. The coordination of transcription activation in nuclei and mitochondria by the respective receptors is in part realized by their binding to common trans acting elements in the two genomes. Recent evidence points to a role of the mitochondrial receptors in cell survival and apoptosis, exerted by genomic and nongenomic mechanisms. The identification of additional receptors of the superfamily of nuclear receptors and of other nuclear transcription factors in mitochondria increases their arsenal of regulatory molecules and further underlines the central role of these organelles in the integration of growth, metabolic, and cell survival signals.2008 IUBMB IUBMB Life, 60(4): [210][211][212][213][214][215][216][217][218][219][220][221][222][223] 2008

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“…GR-dependent genomic effects may also be mitochondrial as well as the well-established nuclear (Scheller et al, 2000;Moutsatsou et al, 2001), and GCs can affect brain mitochondrial function in vitro (Morin et al, 2000). Nevertheless, GR-dependent effects, rapid or delayed, are mediated during periods of high GC concentrations, due to the comparatively low affinity of GRs towards cortisol and corticosterone.…”

Section: How Is Gc Rhythmicity Biologically Perceived By the Brain?mentioning

confidence: 99%

Temporal control of glucocorticoid neurodynamics and its relevance for brain homeostasis, neuropathology and glucocorticoid-based therapeutics

Kalafatakis

Russell

Ζάρρος³

et al. 2016

Neuroscience & Biobehavioral Reviews

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Glucocorticoids mediate plethora of actions throughout the human body. Within the brain, they modulate aspects of immune system and neuroinflammatory processes, interfere with cellular metabolism and viability, interact with systems of neurotransmission and regulate neural rhythms. The influence of glucocorticoids on memory and emotional behaviour is well known and there is increasing evidence for their involvement in many neuropsychiatric pathologies. These effects, which at times can be in opposing directions, depend not only on the concentration of glucocorticoids but also the duration of their presence, the temporal relationship between their fluctuations, the co-influence of other stimuli, and the overall state of brain activity. Moreover, they are region-and cell type-specific. The molecular basis of such diversity of effects lies on the orchestration of the spatiotemporal interplay between glucocorticoid-and mineralocorticoid receptors, and is achieved through complex dynamics, mainly mediated via the circadian and ultradian pattern of glucocorticoid secretion. More sophisticated methodologies are therefore required to better approach the study of these hormones and improve the effectiveness of glucocorticoid-based therapeutics.

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Localization of the Glucocorticoid Receptor in Rat Brain Mitochondria

Cited by 102 publications

References 42 publications

Dynamic molecular and anatomical changes in the glucocorticoid receptor in human cortical development

Dynamic molecular and anatomical changes in the glucocorticoid receptor in human cortical development

Steroid and thyroid hormone receptors in mitochondria

Temporal control of glucocorticoid neurodynamics and its relevance for brain homeostasis, neuropathology and glucocorticoid-based therapeutics

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