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LitCovid-PD-FMA-UBERON

LitCovid-PD-MONDO

{"project":"LitCovid-PD-MONDO","denotations":[{"id":"T134","span":{"begin":33,"end":46},"obj":"Disease"},{"id":"T135","span":{"begin":165,"end":171},"obj":"Disease"},{"id":"T136","span":{"begin":2129,"end":2135},"obj":"Disease"}],"attributes":[{"id":"A134","pred":"mondo_id","subj":"T134","obj":"http://purl.obolibrary.org/obo/MONDO_0005527"},{"id":"A135","pred":"mondo_id","subj":"T135","obj":"http://purl.obolibrary.org/obo/MONDO_0021178"},{"id":"A136","pred":"mondo_id","subj":"T136","obj":"http://purl.obolibrary.org/obo/MONDO_0021178"}],"text":"Besides accentuating HIV-induced neurotoxicity via glial-mediated mechanisms, morphine appears to converge with HIV Tat to dysregulate ion homeostasis and dendritic injury through potential direct actions on neurons, even though some contributions of glia cannot be excluded in this study (Fitting et al. 2014a). Combined morphine and Tat exposure accelerates the formation of Tat-induced focal dendritic varicosities/swelling via a MOR-related mechanism that was caused by focal increases in Na+ influx and [Ca2+]i, an overload of Na+/K+-ATPase, ATP depletion, and a collapse in mitochondrial inner membrane potential (Fitting et al. 2014a). Importantly, morphine’s additive effects were mediated via a MOR-related mechanism, as the exacerbating effects of morphine were absent in neurons from MOR knockout mice, thus excluding TLR4 involvement (Fitting et al. 2014a). Further, morphine exacerbated Tat-dependent focal losses in ion homeostasis by mobilizing [Ca2+]i through ryanodine-2 (RyR2)-sensitive sites (Fitting et al. 2014a) (Fig. 2). Although morphine typically acts via MOR in an inhibitory manner by activating Gi/o-proteins (Sharma et al. 1977; Moises et al. 1994; Al-Hasani and Bruchas 2011), MOR-dependent stimulation of PI3-kinase and Ca2+ mobilization (Leopoldt et al. 1998) in neurons via the Gβγ protein subunit (Mathews et al. 2008) is presumed operative here (Fig. 2).\nFig. 2 Morphine exacerbates the excitotoxic effects of HIV Tat by mobilizing Ca2+ from ryanodine (RyR)-sensitive internal stores. (a) Tat-induced increases in [Ca2+]i were not attenuated by ryanodine, whereas ryanodine and pyruvate attenuate combined Tat and morphine-induced increases in [Ca2+]i. Nimodipine (L-type Ca2+ channel blocker) and dantrolene did not show any effects. (b) Average [Ca2+]i over 10 min indicated ryanodine significantly blocked combined Tat and morphine-induced increases in [Ca2+]i, whereas no effects were noted for nimodipine, dantrolene, or pyruvate. *p \u003c 0.05 vs. control, #p \u003c 0.05 vs. Tat 50 nM, §p \u003c 0.05 vs. TM, TM: Tat 50 nM + Morphine 500 nM. (c) Summary of HIV-1 Tat and morphine interactive neuronal injury in striatal medium spiny neurons. Combined Tat and morphine promotes structural and functional defects in dendrites via α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPAR), N-methyl-D-aspartic acid receptors (NMDAR), and MOR, causing influxes of Na+ and/or Ca2+, compensatory increases in Na+/K+-dependent ATPase activity, and a rapid loss in ATP mobilization with an inability to extrude excess Na+ via Na+/K+-ATPase caused by mitochondrial hyperpolarization. Dysregulation of [Ca2+]i homeostasis by combined Tat and morphine appears to be mediated downstream of [Na+]i at the level of calcium mobilization, which in turn appears to be regulated via ryanodine (RyR)-sensitive sites, and enhanced by morphine exposure likely via MOR-dependent stimulation of PI3-kinase and Ca2+ mobilization via the Gβγ protein subunit. (a-b) Modified and reprinted with permission from Fitting et al. (2014a)"}

LitCovid-PD-CLO

{"project":"LitCovid-PD-CLO","denotations":[{"id":"T591","span":{"begin":431,"end":432},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"},{"id":"T592","span":{"begin":566,"end":567},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"},{"id":"T593","span":{"begin":600,"end":608},"obj":"http://purl.obolibrary.org/obo/UBERON_0000158"},{"id":"T594","span":{"begin":702,"end":703},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"},{"id":"T595","span":{"begin":1112,"end":1122},"obj":"http://purl.obolibrary.org/obo/CLO_0001658"},{"id":"T596","span":{"begin":1521,"end":1522},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"},{"id":"T597","span":{"begin":1771,"end":1772},"obj":"http://purl.obolibrary.org/obo/CLO_0001021"},{"id":"T598","span":{"begin":2468,"end":2476},"obj":"http://purl.obolibrary.org/obo/CLO_0001658"},{"id":"T599","span":{"begin":2482,"end":2483},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"},{"id":"T600","span":{"begin":2976,"end":2977},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"},{"id":"T601","span":{"begin":2978,"end":2979},"obj":"http://purl.obolibrary.org/obo/CLO_0001021"}],"text":"Besides accentuating HIV-induced neurotoxicity via glial-mediated mechanisms, morphine appears to converge with HIV Tat to dysregulate ion homeostasis and dendritic injury through potential direct actions on neurons, even though some contributions of glia cannot be excluded in this study (Fitting et al. 2014a). Combined morphine and Tat exposure accelerates the formation of Tat-induced focal dendritic varicosities/swelling via a MOR-related mechanism that was caused by focal increases in Na+ influx and [Ca2+]i, an overload of Na+/K+-ATPase, ATP depletion, and a collapse in mitochondrial inner membrane potential (Fitting et al. 2014a). Importantly, morphine’s additive effects were mediated via a MOR-related mechanism, as the exacerbating effects of morphine were absent in neurons from MOR knockout mice, thus excluding TLR4 involvement (Fitting et al. 2014a). Further, morphine exacerbated Tat-dependent focal losses in ion homeostasis by mobilizing [Ca2+]i through ryanodine-2 (RyR2)-sensitive sites (Fitting et al. 2014a) (Fig. 2). Although morphine typically acts via MOR in an inhibitory manner by activating Gi/o-proteins (Sharma et al. 1977; Moises et al. 1994; Al-Hasani and Bruchas 2011), MOR-dependent stimulation of PI3-kinase and Ca2+ mobilization (Leopoldt et al. 1998) in neurons via the Gβγ protein subunit (Mathews et al. 2008) is presumed operative here (Fig. 2).\nFig. 2 Morphine exacerbates the excitotoxic effects of HIV Tat by mobilizing Ca2+ from ryanodine (RyR)-sensitive internal stores. (a) Tat-induced increases in [Ca2+]i were not attenuated by ryanodine, whereas ryanodine and pyruvate attenuate combined Tat and morphine-induced increases in [Ca2+]i. Nimodipine (L-type Ca2+ channel blocker) and dantrolene did not show any effects. (b) Average [Ca2+]i over 10 min indicated ryanodine significantly blocked combined Tat and morphine-induced increases in [Ca2+]i, whereas no effects were noted for nimodipine, dantrolene, or pyruvate. *p \u003c 0.05 vs. control, #p \u003c 0.05 vs. Tat 50 nM, §p \u003c 0.05 vs. TM, TM: Tat 50 nM + Morphine 500 nM. (c) Summary of HIV-1 Tat and morphine interactive neuronal injury in striatal medium spiny neurons. Combined Tat and morphine promotes structural and functional defects in dendrites via α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPAR), N-methyl-D-aspartic acid receptors (NMDAR), and MOR, causing influxes of Na+ and/or Ca2+, compensatory increases in Na+/K+-dependent ATPase activity, and a rapid loss in ATP mobilization with an inability to extrude excess Na+ via Na+/K+-ATPase caused by mitochondrial hyperpolarization. Dysregulation of [Ca2+]i homeostasis by combined Tat and morphine appears to be mediated downstream of [Na+]i at the level of calcium mobilization, which in turn appears to be regulated via ryanodine (RyR)-sensitive sites, and enhanced by morphine exposure likely via MOR-dependent stimulation of PI3-kinase and Ca2+ mobilization via the Gβγ protein subunit. (a-b) Modified and reprinted with permission from Fitting et al. (2014a)"}

LitCovid-PD-CHEBI

LitCovid-PubTator

LitCovid-PD-GO-BP

{"project":"LitCovid-PD-GO-BP","denotations":[{"id":"T85","span":{"begin":135,"end":150},"obj":"http://purl.obolibrary.org/obo/GO_0050801"},{"id":"T86","span":{"begin":139,"end":150},"obj":"http://purl.obolibrary.org/obo/GO_0042592"},{"id":"T87","span":{"begin":364,"end":373},"obj":"http://purl.obolibrary.org/obo/GO_0009058"},{"id":"T88","span":{"begin":930,"end":945},"obj":"http://purl.obolibrary.org/obo/GO_0050801"},{"id":"T89","span":{"begin":934,"end":945},"obj":"http://purl.obolibrary.org/obo/GO_0042592"},{"id":"T90","span":{"begin":2641,"end":2652},"obj":"http://purl.obolibrary.org/obo/GO_0042592"},{"id":"T91","span":{"begin":2742,"end":2762},"obj":"http://purl.obolibrary.org/obo/GO_0051209"}],"text":"Besides accentuating HIV-induced neurotoxicity via glial-mediated mechanisms, morphine appears to converge with HIV Tat to dysregulate ion homeostasis and dendritic injury through potential direct actions on neurons, even though some contributions of glia cannot be excluded in this study (Fitting et al. 2014a). Combined morphine and Tat exposure accelerates the formation of Tat-induced focal dendritic varicosities/swelling via a MOR-related mechanism that was caused by focal increases in Na+ influx and [Ca2+]i, an overload of Na+/K+-ATPase, ATP depletion, and a collapse in mitochondrial inner membrane potential (Fitting et al. 2014a). Importantly, morphine’s additive effects were mediated via a MOR-related mechanism, as the exacerbating effects of morphine were absent in neurons from MOR knockout mice, thus excluding TLR4 involvement (Fitting et al. 2014a). Further, morphine exacerbated Tat-dependent focal losses in ion homeostasis by mobilizing [Ca2+]i through ryanodine-2 (RyR2)-sensitive sites (Fitting et al. 2014a) (Fig. 2). Although morphine typically acts via MOR in an inhibitory manner by activating Gi/o-proteins (Sharma et al. 1977; Moises et al. 1994; Al-Hasani and Bruchas 2011), MOR-dependent stimulation of PI3-kinase and Ca2+ mobilization (Leopoldt et al. 1998) in neurons via the Gβγ protein subunit (Mathews et al. 2008) is presumed operative here (Fig. 2).\nFig. 2 Morphine exacerbates the excitotoxic effects of HIV Tat by mobilizing Ca2+ from ryanodine (RyR)-sensitive internal stores. (a) Tat-induced increases in [Ca2+]i were not attenuated by ryanodine, whereas ryanodine and pyruvate attenuate combined Tat and morphine-induced increases in [Ca2+]i. Nimodipine (L-type Ca2+ channel blocker) and dantrolene did not show any effects. (b) Average [Ca2+]i over 10 min indicated ryanodine significantly blocked combined Tat and morphine-induced increases in [Ca2+]i, whereas no effects were noted for nimodipine, dantrolene, or pyruvate. *p \u003c 0.05 vs. control, #p \u003c 0.05 vs. Tat 50 nM, §p \u003c 0.05 vs. TM, TM: Tat 50 nM + Morphine 500 nM. (c) Summary of HIV-1 Tat and morphine interactive neuronal injury in striatal medium spiny neurons. Combined Tat and morphine promotes structural and functional defects in dendrites via α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPAR), N-methyl-D-aspartic acid receptors (NMDAR), and MOR, causing influxes of Na+ and/or Ca2+, compensatory increases in Na+/K+-dependent ATPase activity, and a rapid loss in ATP mobilization with an inability to extrude excess Na+ via Na+/K+-ATPase caused by mitochondrial hyperpolarization. Dysregulation of [Ca2+]i homeostasis by combined Tat and morphine appears to be mediated downstream of [Na+]i at the level of calcium mobilization, which in turn appears to be regulated via ryanodine (RyR)-sensitive sites, and enhanced by morphine exposure likely via MOR-dependent stimulation of PI3-kinase and Ca2+ mobilization via the Gβγ protein subunit. (a-b) Modified and reprinted with permission from Fitting et al. (2014a)"}

LitCovid-sentences

{"project":"LitCovid-sentences","denotations":[{"id":"T718","span":{"begin":0,"end":304},"obj":"Sentence"},{"id":"T719","span":{"begin":305,"end":312},"obj":"Sentence"},{"id":"T720","span":{"begin":313,"end":634},"obj":"Sentence"},{"id":"T721","span":{"begin":635,"end":642},"obj":"Sentence"},{"id":"T722","span":{"begin":643,"end":861},"obj":"Sentence"},{"id":"T723","span":{"begin":862,"end":869},"obj":"Sentence"},{"id":"T724","span":{"begin":870,"end":1026},"obj":"Sentence"},{"id":"T725","span":{"begin":1027,"end":1043},"obj":"Sentence"},{"id":"T726","span":{"begin":1044,"end":1151},"obj":"Sentence"},{"id":"T727","span":{"begin":1152,"end":1171},"obj":"Sentence"},{"id":"T728","span":{"begin":1172,"end":1285},"obj":"Sentence"},{"id":"T729","span":{"begin":1286,"end":1346},"obj":"Sentence"},{"id":"T730","span":{"begin":1347,"end":1389},"obj":"Sentence"},{"id":"T731","span":{"begin":1390,"end":1687},"obj":"Sentence"},{"id":"T732","span":{"begin":1688,"end":2040},"obj":"Sentence"},{"id":"T733","span":{"begin":2041,"end":2169},"obj":"Sentence"},{"id":"T734","span":{"begin":2170,"end":2615},"obj":"Sentence"},{"id":"T735","span":{"begin":2616,"end":3047},"obj":"Sentence"}],"namespaces":[{"prefix":"_base","uri":"http://pubannotation.org/ontology/tao.owl#"}],"text":"Besides accentuating HIV-induced neurotoxicity via glial-mediated mechanisms, morphine appears to converge with HIV Tat to dysregulate ion homeostasis and dendritic injury through potential direct actions on neurons, even though some contributions of glia cannot be excluded in this study (Fitting et al. 2014a). Combined morphine and Tat exposure accelerates the formation of Tat-induced focal dendritic varicosities/swelling via a MOR-related mechanism that was caused by focal increases in Na+ influx and [Ca2+]i, an overload of Na+/K+-ATPase, ATP depletion, and a collapse in mitochondrial inner membrane potential (Fitting et al. 2014a). Importantly, morphine’s additive effects were mediated via a MOR-related mechanism, as the exacerbating effects of morphine were absent in neurons from MOR knockout mice, thus excluding TLR4 involvement (Fitting et al. 2014a). Further, morphine exacerbated Tat-dependent focal losses in ion homeostasis by mobilizing [Ca2+]i through ryanodine-2 (RyR2)-sensitive sites (Fitting et al. 2014a) (Fig. 2). Although morphine typically acts via MOR in an inhibitory manner by activating Gi/o-proteins (Sharma et al. 1977; Moises et al. 1994; Al-Hasani and Bruchas 2011), MOR-dependent stimulation of PI3-kinase and Ca2+ mobilization (Leopoldt et al. 1998) in neurons via the Gβγ protein subunit (Mathews et al. 2008) is presumed operative here (Fig. 2).\nFig. 2 Morphine exacerbates the excitotoxic effects of HIV Tat by mobilizing Ca2+ from ryanodine (RyR)-sensitive internal stores. (a) Tat-induced increases in [Ca2+]i were not attenuated by ryanodine, whereas ryanodine and pyruvate attenuate combined Tat and morphine-induced increases in [Ca2+]i. Nimodipine (L-type Ca2+ channel blocker) and dantrolene did not show any effects. (b) Average [Ca2+]i over 10 min indicated ryanodine significantly blocked combined Tat and morphine-induced increases in [Ca2+]i, whereas no effects were noted for nimodipine, dantrolene, or pyruvate. *p \u003c 0.05 vs. control, #p \u003c 0.05 vs. Tat 50 nM, §p \u003c 0.05 vs. TM, TM: Tat 50 nM + Morphine 500 nM. (c) Summary of HIV-1 Tat and morphine interactive neuronal injury in striatal medium spiny neurons. Combined Tat and morphine promotes structural and functional defects in dendrites via α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPAR), N-methyl-D-aspartic acid receptors (NMDAR), and MOR, causing influxes of Na+ and/or Ca2+, compensatory increases in Na+/K+-dependent ATPase activity, and a rapid loss in ATP mobilization with an inability to extrude excess Na+ via Na+/K+-ATPase caused by mitochondrial hyperpolarization. Dysregulation of [Ca2+]i homeostasis by combined Tat and morphine appears to be mediated downstream of [Na+]i at the level of calcium mobilization, which in turn appears to be regulated via ryanodine (RyR)-sensitive sites, and enhanced by morphine exposure likely via MOR-dependent stimulation of PI3-kinase and Ca2+ mobilization via the Gβγ protein subunit. (a-b) Modified and reprinted with permission from Fitting et al. (2014a)"}

2_test

{"project":"2_test","denotations":[{"id":"32876803-269396-62958101","span":{"begin":1152,"end":1156},"obj":"269396"},{"id":"32876803-7931552-62958102","span":{"begin":1172,"end":1176},"obj":"7931552"},{"id":"32876803-22020140-62958103","span":{"begin":1200,"end":1204},"obj":"22020140"}],"text":"Besides accentuating HIV-induced neurotoxicity via glial-mediated mechanisms, morphine appears to converge with HIV Tat to dysregulate ion homeostasis and dendritic injury through potential direct actions on neurons, even though some contributions of glia cannot be excluded in this study (Fitting et al. 2014a). Combined morphine and Tat exposure accelerates the formation of Tat-induced focal dendritic varicosities/swelling via a MOR-related mechanism that was caused by focal increases in Na+ influx and [Ca2+]i, an overload of Na+/K+-ATPase, ATP depletion, and a collapse in mitochondrial inner membrane potential (Fitting et al. 2014a). Importantly, morphine’s additive effects were mediated via a MOR-related mechanism, as the exacerbating effects of morphine were absent in neurons from MOR knockout mice, thus excluding TLR4 involvement (Fitting et al. 2014a). Further, morphine exacerbated Tat-dependent focal losses in ion homeostasis by mobilizing [Ca2+]i through ryanodine-2 (RyR2)-sensitive sites (Fitting et al. 2014a) (Fig. 2). Although morphine typically acts via MOR in an inhibitory manner by activating Gi/o-proteins (Sharma et al. 1977; Moises et al. 1994; Al-Hasani and Bruchas 2011), MOR-dependent stimulation of PI3-kinase and Ca2+ mobilization (Leopoldt et al. 1998) in neurons via the Gβγ protein subunit (Mathews et al. 2008) is presumed operative here (Fig. 2).\nFig. 2 Morphine exacerbates the excitotoxic effects of HIV Tat by mobilizing Ca2+ from ryanodine (RyR)-sensitive internal stores. (a) Tat-induced increases in [Ca2+]i were not attenuated by ryanodine, whereas ryanodine and pyruvate attenuate combined Tat and morphine-induced increases in [Ca2+]i. Nimodipine (L-type Ca2+ channel blocker) and dantrolene did not show any effects. (b) Average [Ca2+]i over 10 min indicated ryanodine significantly blocked combined Tat and morphine-induced increases in [Ca2+]i, whereas no effects were noted for nimodipine, dantrolene, or pyruvate. *p \u003c 0.05 vs. control, #p \u003c 0.05 vs. Tat 50 nM, §p \u003c 0.05 vs. TM, TM: Tat 50 nM + Morphine 500 nM. (c) Summary of HIV-1 Tat and morphine interactive neuronal injury in striatal medium spiny neurons. Combined Tat and morphine promotes structural and functional defects in dendrites via α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPAR), N-methyl-D-aspartic acid receptors (NMDAR), and MOR, causing influxes of Na+ and/or Ca2+, compensatory increases in Na+/K+-dependent ATPase activity, and a rapid loss in ATP mobilization with an inability to extrude excess Na+ via Na+/K+-ATPase caused by mitochondrial hyperpolarization. Dysregulation of [Ca2+]i homeostasis by combined Tat and morphine appears to be mediated downstream of [Na+]i at the level of calcium mobilization, which in turn appears to be regulated via ryanodine (RyR)-sensitive sites, and enhanced by morphine exposure likely via MOR-dependent stimulation of PI3-kinase and Ca2+ mobilization via the Gβγ protein subunit. (a-b) Modified and reprinted with permission from Fitting et al. (2014a)"}

PMC:7463108 / 49461-52508 JSONTXT

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PMC:7463108 / 49461-52508 JSON TXT