The cell survival kinase SGK1 and its targets FOXO3a and NDRG1 in aged human brain
Identifieur interne : 001111 ( Main/Exploration ); précédent : 001110; suivant : 001112The cell survival kinase SGK1 and its targets FOXO3a and NDRG1 in aged human brain
Auteurs : P. Sahin [Royaume-Uni] ; C. Mccaig [Royaume-Uni] ; J. Jeevahan [Royaume-Uni] ; J. T. Murray [Irlande (pays)] ; A. H. Hainsworth [Royaume-Uni]Source :
- Neuropathology and Applied Neurobiology [ 0305-1846 ] ; 2013-10.
English descriptors
- Teeft :
- Adjacent sections, Amyloid plaques, Apoptotic cell death, Authors neuropathology, Axonal tracts, Braak stage, Brain disease, Brain tissue, British neuropathological society, Canonical sgk1, Cell cycle, Cell death, Cell survival, Cell survival kinase sgk1, Cerebral cortex, Chronic neurodegeneration, Control case, Control subjects, Cortical, Cortical neurones, Cortical tissue, Cortical tissue lysates, Critical review, Cytoplasmic, Cytoplasmic foxo3a, Data analysis, Disease brain, Foxo3a, Growth factor withdrawal, Housekeeping protein, Human brain, Human sgk1, Immunohistochemical labelling, John radcliffe hospital, Kinase, Labelling, Lang, Large cells, Large process, London neurodegenerative diseases brain bank, Long arrows, Lysates, Medical centre, Mouse brain, Ndrg1, Ndrg1 phosphorylated, Neurobiology, Neuronal, Neuronal cells, Neurones, Neuropathological, Neuropathology, Nuclear chromatin, Nuclear foxo3a, Nuclear foxo3a labelling, Nuclear labelling, Nuclear localization signal, Nuclear sgk1, Nucleus cytoplasm, Oxidative stress, Perivascular macrophages, Phosphorylation, Polygonal cells, Primary antibodies, Primary cultures, Proc natl acad, Protective response, Protein kinase, Range years, Recombinant sgk1, Room temperature, Sahin, Scale bars, Semiquantitative densitometry, Semiquantitative densitometry data, Sgk1, Sgk1 abundance, Sgk1 activity, Sgk1 antibody, Sgk1 antiserum, Sgk1 labelling, Short arrows, Splice variants, Targets foxo3a, Thomas willis oxford brain collection, Total ndrg1, Transcription, Transcription factor, Transcription factor foxo3a, Vascular cells, Visible nucleus, Western analysis, Western blots, Western immunoblot analysis, White matter.
Abstract
Aims: Serum‐ and glucocorticoid‐inducible kinase 1 (SGK1) protects neuronal cells from injury stimuli in vitro, and exerts anti‐apoptotic effects via downstream targets including the forkhead‐like transcription factor FOXO3a. SGK1 is a homolog of Akt, a related survival kinase that is up‐regulated in Alzheimer's disease (AD). Here we aimed to examine the expression pattern of SGK1 and FOXO3a in aged human cerebral cortex. Methods: Cortical tissue from aged donors without brain disease (aged controls, AC, n = 19) and from severe AD patients (Braak stage V‐VI; n = 14) were examined by immunohistochemistry and immunoblot analysis. Results: SGK1 was present in all samples (detected by immunohistochemistry and immunoblotting). Large cortical neuronal cells were strongly positive for SGK1, with predominantly nuclear labelling. Some astrocytes and oligodendrocytes were also labelled. SGK1 was not seen in nerve tracts (axons or myelin) and rarely seen in CD68‐positive cells (microglia, perivascular macrophages) or vascular cells (myocytes or endothelia). The fraction of large cortical neurones with nuclear FOXO3a was lower in AD cases relative to AC (54%, 70%, respectively, P < 0.001). In immunoblots no difference in SGK1 abundance was detected between AC and AD tissues. Phosphorylation of NDRG1 (an SGK1‐specific target) was greater in AD, relative to AC cases (approximately twofold, P = 0.023). Conclusions: Neuronal expression of SGK1 in aged human brain and its nuclear compartmentalization suggest a possible neuroprotective role. FOXO3a and NDRG1 data suggest augmented SGK1 activity (as reported for Akt) in severe AD. Increased intracellular SGK1 may complement enhanced Akt, with a distinct subcellular localization.
Url:
DOI: 10.1111/nan.12023
Affiliations:
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Hainsworth</name><affiliation wicri:level="4"><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Stroke & Dementia Research Centre, Division of Clinical Sciences, St Georges University of London, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName><orgName type="university">Université de Londres</orgName></affiliation><affiliation wicri:level="1"><country wicri:rule="url">Royaume-Uni</country></affiliation></author></analytic><monogr></monogr><series><title level="j" type="main">Neuropathology and Applied Neurobiology</title><title level="j" type="alt">NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY</title><idno type="ISSN">0305-1846</idno><idno type="eISSN">1365-2990</idno><imprint><biblScope unit="vol">39</biblScope><biblScope unit="issue">6</biblScope><biblScope unit="page" from="623">623</biblScope><biblScope unit="page" to="633">633</biblScope><biblScope unit="page-count">11</biblScope><date type="published" when="2013-10">2013-10</date></imprint><idno type="ISSN">0305-1846</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0305-1846</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="Teeft" xml:lang="en"><term>Adjacent sections</term><term>Amyloid plaques</term><term>Apoptotic cell death</term><term>Authors neuropathology</term><term>Axonal tracts</term><term>Braak stage</term><term>Brain disease</term><term>Brain tissue</term><term>British neuropathological society</term><term>Canonical sgk1</term><term>Cell cycle</term><term>Cell death</term><term>Cell survival</term><term>Cell survival kinase sgk1</term><term>Cerebral cortex</term><term>Chronic neurodegeneration</term><term>Control case</term><term>Control subjects</term><term>Cortical</term><term>Cortical neurones</term><term>Cortical tissue</term><term>Cortical tissue lysates</term><term>Critical review</term><term>Cytoplasmic</term><term>Cytoplasmic foxo3a</term><term>Data analysis</term><term>Disease brain</term><term>Foxo3a</term><term>Growth factor withdrawal</term><term>Housekeeping protein</term><term>Human brain</term><term>Human sgk1</term><term>Immunohistochemical labelling</term><term>John radcliffe hospital</term><term>Kinase</term><term>Labelling</term><term>Lang</term><term>Large cells</term><term>Large process</term><term>London neurodegenerative diseases brain bank</term><term>Long arrows</term><term>Lysates</term><term>Medical centre</term><term>Mouse brain</term><term>Ndrg1</term><term>Ndrg1 phosphorylated</term><term>Neurobiology</term><term>Neuronal</term><term>Neuronal cells</term><term>Neurones</term><term>Neuropathological</term><term>Neuropathology</term><term>Nuclear chromatin</term><term>Nuclear foxo3a</term><term>Nuclear foxo3a labelling</term><term>Nuclear labelling</term><term>Nuclear localization signal</term><term>Nuclear sgk1</term><term>Nucleus cytoplasm</term><term>Oxidative stress</term><term>Perivascular macrophages</term><term>Phosphorylation</term><term>Polygonal cells</term><term>Primary antibodies</term><term>Primary cultures</term><term>Proc natl acad</term><term>Protective response</term><term>Protein kinase</term><term>Range years</term><term>Recombinant sgk1</term><term>Room temperature</term><term>Sahin</term><term>Scale bars</term><term>Semiquantitative densitometry</term><term>Semiquantitative densitometry data</term><term>Sgk1</term><term>Sgk1 abundance</term><term>Sgk1 activity</term><term>Sgk1 antibody</term><term>Sgk1 antiserum</term><term>Sgk1 labelling</term><term>Short arrows</term><term>Splice variants</term><term>Targets foxo3a</term><term>Thomas willis oxford brain collection</term><term>Total ndrg1</term><term>Transcription</term><term>Transcription factor</term><term>Transcription factor foxo3a</term><term>Vascular cells</term><term>Visible nucleus</term><term>Western analysis</term><term>Western blots</term><term>Western immunoblot analysis</term><term>White matter</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract">Aims: Serum‐ and glucocorticoid‐inducible kinase 1 (SGK1) protects neuronal cells from injury stimuli in vitro, and exerts anti‐apoptotic effects via downstream targets including the forkhead‐like transcription factor FOXO3a. SGK1 is a homolog of Akt, a related survival kinase that is up‐regulated in Alzheimer's disease (AD). Here we aimed to examine the expression pattern of SGK1 and FOXO3a in aged human cerebral cortex. Methods: Cortical tissue from aged donors without brain disease (aged controls, AC, n = 19) and from severe AD patients (Braak stage V‐VI; n = 14) were examined by immunohistochemistry and immunoblot analysis. Results: SGK1 was present in all samples (detected by immunohistochemistry and immunoblotting). Large cortical neuronal cells were strongly positive for SGK1, with predominantly nuclear labelling. Some astrocytes and oligodendrocytes were also labelled. SGK1 was not seen in nerve tracts (axons or myelin) and rarely seen in CD68‐positive cells (microglia, perivascular macrophages) or vascular cells (myocytes or endothelia). The fraction of large cortical neurones with nuclear FOXO3a was lower in AD cases relative to AC (54%, 70%, respectively, P < 0.001). In immunoblots no difference in SGK1 abundance was detected between AC and AD tissues. Phosphorylation of NDRG1 (an SGK1‐specific target) was greater in AD, relative to AC cases (approximately twofold, P = 0.023). Conclusions: Neuronal expression of SGK1 in aged human brain and its nuclear compartmentalization suggest a possible neuroprotective role. FOXO3a and NDRG1 data suggest augmented SGK1 activity (as reported for Akt) in severe AD. Increased intracellular SGK1 may complement enhanced Akt, with a distinct subcellular localization.</div></front></TEI><affiliations><list><country><li>Irlande (pays)</li><li>Royaume-Uni</li></country><region><li>Angleterre</li><li>Grand Londres</li></region><settlement><li>Londres</li></settlement><orgName><li>Université de Londres</li></orgName></list><tree><country name="Royaume-Uni"><region name="Angleterre"><name sortKey="Sahin, P" sort="Sahin, P" uniqKey="Sahin P" first="P." last="Sahin">P. Sahin</name></region><name sortKey="Hainsworth, A H" sort="Hainsworth, A H" uniqKey="Hainsworth A" first="A. H." last="Hainsworth">A. H. Hainsworth</name><name sortKey="Hainsworth, A H" sort="Hainsworth, A H" uniqKey="Hainsworth A" first="A. H." last="Hainsworth">A. H. Hainsworth</name><name sortKey="Jeevahan, J" sort="Jeevahan, J" uniqKey="Jeevahan J" first="J." last="Jeevahan">J. Jeevahan</name><name sortKey="Mccaig, C" sort="Mccaig, C" uniqKey="Mccaig C" first="C." last="Mccaig">C. Mccaig</name></country><country name="Irlande (pays)"><noRegion><name sortKey="Murray, J T" sort="Murray, J T" uniqKey="Murray J" first="J. T." last="Murray">J. T. Murray</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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