PMC:7463108 / 47354-48991 JSONTXT

{"project":"LitCovid-PD-FMA-UBERON","denotations":[{"id":"T477","span":{"begin":10,"end":20},"obj":"Body_part"},{"id":"T478","span":{"begin":33,"end":36},"obj":"Body_part"},{"id":"T5102","span":{"begin":53,"end":62},"obj":"Body_part"},{"id":"T480","span":{"begin":198,"end":207},"obj":"Body_part"},{"id":"T481","span":{"begin":425,"end":434},"obj":"Body_part"},{"id":"T482","span":{"begin":624,"end":633},"obj":"Body_part"},{"id":"T483","span":{"begin":703,"end":711},"obj":"Body_part"},{"id":"T484","span":{"begin":956,"end":965},"obj":"Body_part"},{"id":"T485","span":{"begin":1295,"end":1298},"obj":"Body_part"},{"id":"T486","span":{"begin":1323,"end":1332},"obj":"Body_part"},{"id":"T487","span":{"begin":1373,"end":1381},"obj":"Body_part"},{"id":"T488","span":{"begin":1422,"end":1430},"obj":"Body_part"}],"attributes":[{"id":"A477","pred":"fma_id","subj":"T477","obj":"http://purl.org/sig/ont/fma/fma54537"},{"id":"A478","pred":"fma_id","subj":"T478","obj":"http://purl.org/sig/ont/fma/fma278683"},{"id":"A479","pred":"fma_id","subj":"T5102","obj":"http://purl.org/sig/ont/fma/fma68923"},{"id":"A480","pred":"fma_id","subj":"T480","obj":"http://purl.org/sig/ont/fma/fma84050"},{"id":"A481","pred":"fma_id","subj":"T481","obj":"http://purl.org/sig/ont/fma/fma68923"},{"id":"A482","pred":"fma_id","subj":"T482","obj":"http://purl.org/sig/ont/fma/fma84050"},{"id":"A483","pred":"fma_id","subj":"T483","obj":"http://purl.org/sig/ont/fma/fma84050"},{"id":"A484","pred":"fma_id","subj":"T484","obj":"http://purl.org/sig/ont/fma/fma68923"},{"id":"A485","pred":"fma_id","subj":"T485","obj":"http://purl.org/sig/ont/fma/fma278683"},{"id":"A486","pred":"fma_id","subj":"T486","obj":"http://purl.org/sig/ont/fma/fma68923"},{"id":"A487","pred":"fma_id","subj":"T487","obj":"http://purl.org/sig/ont/fma/fma84050"},{"id":"A488","pred":"fma_id","subj":"T488","obj":"http://purl.org/sig/ont/fma/fma84050"}],"text":"Unlike in astrocytes, opiate and HIV interactions in microglia tend to be self-limiting (Turchan-Cholewo et al. 2009). Opiates initially trigger large increases in the production of proinflammatory cytokines (Hauser, unpublished), reactive oxygen (ROS) and nitrogen (RNS) species (Turchan-Cholewo et al. 2009), and the release of glutamate (Gupta et al. 2010) and ATP (Sorrell and Hauser 2014) extracellularly in Tat-exposed microglia. The release of glutamate is mediated by the catalytic subunit of the cystine-glutamate antiporter xc− (xCT) (Gupta et al. 2010). Interestingly, following acute increases in the release of cytokines (e.g., TNF-α; unpublished), morphine no longer increases Tat-induced cytokine levels at 24 h; instead, their levels are reduced by opiate-dependent proteasome inhibition. The proteasome inhibitor, MG115, mimics the effects of morphine in decreasing proteasome activity at 24 h and blocks TNFα, IL-6, and CCL2 release from microglia, but does not increase ROS or RNS production (Turchan-Cholewo et al. 2009). The ubiquitin proteasome system (UPS) is typically viewed as contributing to opiate tolerance and physical dependence by modulating MOR downregulation (Massaly et al. 2014; Caputi et al. 2019), rather than MOR activity constraining the UPS. Thus, while HIV-exposed, MOR-expressing microglia show a burst of ROS and proinflammatory cytokine production in response to morphine, the cytokine release collapses within 24 h seemingly because sustained opiate exposure inhibits the UPS thereby preventing degradation of the IκB subunit and nuclear translocation of NF-κB (Turchan-Cholewo et al. 2009)."}

{"project":"LitCovid-PD-MONDO","denotations":[{"id":"T126","span":{"begin":267,"end":270},"obj":"Disease"},{"id":"T128","span":{"begin":996,"end":999},"obj":"Disease"},{"id":"T130","span":{"begin":1075,"end":1078},"obj":"Disease"},{"id":"T131","span":{"begin":1278,"end":1281},"obj":"Disease"},{"id":"T132","span":{"begin":1518,"end":1521},"obj":"Disease"}],"attributes":[{"id":"A126","pred":"mondo_id","subj":"T126","obj":"http://purl.obolibrary.org/obo/MONDO_0009821"},{"id":"A127","pred":"mondo_id","subj":"T126","obj":"http://purl.obolibrary.org/obo/MONDO_0019105"},{"id":"A128","pred":"mondo_id","subj":"T128","obj":"http://purl.obolibrary.org/obo/MONDO_0009821"},{"id":"A129","pred":"mondo_id","subj":"T128","obj":"http://purl.obolibrary.org/obo/MONDO_0019105"},{"id":"A130","pred":"mondo_id","subj":"T130","obj":"http://purl.obolibrary.org/obo/MONDO_0002142"},{"id":"A131","pred":"mondo_id","subj":"T131","obj":"http://purl.obolibrary.org/obo/MONDO_0002142"},{"id":"A132","pred":"mondo_id","subj":"T132","obj":"http://purl.obolibrary.org/obo/MONDO_0002142"}],"text":"Unlike in astrocytes, opiate and HIV interactions in microglia tend to be self-limiting (Turchan-Cholewo et al. 2009). Opiates initially trigger large increases in the production of proinflammatory cytokines (Hauser, unpublished), reactive oxygen (ROS) and nitrogen (RNS) species (Turchan-Cholewo et al. 2009), and the release of glutamate (Gupta et al. 2010) and ATP (Sorrell and Hauser 2014) extracellularly in Tat-exposed microglia. The release of glutamate is mediated by the catalytic subunit of the cystine-glutamate antiporter xc− (xCT) (Gupta et al. 2010). Interestingly, following acute increases in the release of cytokines (e.g., TNF-α; unpublished), morphine no longer increases Tat-induced cytokine levels at 24 h; instead, their levels are reduced by opiate-dependent proteasome inhibition. The proteasome inhibitor, MG115, mimics the effects of morphine in decreasing proteasome activity at 24 h and blocks TNFα, IL-6, and CCL2 release from microglia, but does not increase ROS or RNS production (Turchan-Cholewo et al. 2009). The ubiquitin proteasome system (UPS) is typically viewed as contributing to opiate tolerance and physical dependence by modulating MOR downregulation (Massaly et al. 2014; Caputi et al. 2019), rather than MOR activity constraining the UPS. Thus, while HIV-exposed, MOR-expressing microglia show a burst of ROS and proinflammatory cytokine production in response to morphine, the cytokine release collapses within 24 h seemingly because sustained opiate exposure inhibits the UPS thereby preventing degradation of the IκB subunit and nuclear translocation of NF-κB (Turchan-Cholewo et al. 2009)."}

{"project":"LitCovid-PD-CLO","denotations":[{"id":"T574","span":{"begin":10,"end":20},"obj":"http://purl.obolibrary.org/obo/CL_0000127"},{"id":"T575","span":{"begin":53,"end":62},"obj":"http://purl.obolibrary.org/obo/CL_0000129"},{"id":"T576","span":{"begin":425,"end":434},"obj":"http://purl.obolibrary.org/obo/CL_0000129"},{"id":"T577","span":{"begin":534,"end":536},"obj":"http://purl.obolibrary.org/obo/CLO_0009645"},{"id":"T578","span":{"begin":534,"end":536},"obj":"http://purl.obolibrary.org/obo/CLO_0050824"},{"id":"T579","span":{"begin":894,"end":902},"obj":"http://purl.obolibrary.org/obo/CLO_0001658"},{"id":"T580","span":{"begin":956,"end":965},"obj":"http://purl.obolibrary.org/obo/CL_0000129"},{"id":"T581","span":{"begin":1252,"end":1260},"obj":"http://purl.obolibrary.org/obo/CLO_0001658"},{"id":"T582","span":{"begin":1323,"end":1332},"obj":"http://purl.obolibrary.org/obo/CL_0000129"},{"id":"T583","span":{"begin":1338,"end":1339},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"},{"id":"T584","span":{"begin":1562,"end":1563},"obj":"http://purl.obolibrary.org/obo/CLO_0001021"},{"id":"T585","span":{"begin":1605,"end":1606},"obj":"http://purl.obolibrary.org/obo/CLO_0001021"}],"text":"Unlike in astrocytes, opiate and HIV interactions in microglia tend to be self-limiting (Turchan-Cholewo et al. 2009). Opiates initially trigger large increases in the production of proinflammatory cytokines (Hauser, unpublished), reactive oxygen (ROS) and nitrogen (RNS) species (Turchan-Cholewo et al. 2009), and the release of glutamate (Gupta et al. 2010) and ATP (Sorrell and Hauser 2014) extracellularly in Tat-exposed microglia. The release of glutamate is mediated by the catalytic subunit of the cystine-glutamate antiporter xc− (xCT) (Gupta et al. 2010). Interestingly, following acute increases in the release of cytokines (e.g., TNF-α; unpublished), morphine no longer increases Tat-induced cytokine levels at 24 h; instead, their levels are reduced by opiate-dependent proteasome inhibition. The proteasome inhibitor, MG115, mimics the effects of morphine in decreasing proteasome activity at 24 h and blocks TNFα, IL-6, and CCL2 release from microglia, but does not increase ROS or RNS production (Turchan-Cholewo et al. 2009). The ubiquitin proteasome system (UPS) is typically viewed as contributing to opiate tolerance and physical dependence by modulating MOR downregulation (Massaly et al. 2014; Caputi et al. 2019), rather than MOR activity constraining the UPS. Thus, while HIV-exposed, MOR-expressing microglia show a burst of ROS and proinflammatory cytokine production in response to morphine, the cytokine release collapses within 24 h seemingly because sustained opiate exposure inhibits the UPS thereby preventing degradation of the IκB subunit and nuclear translocation of NF-κB (Turchan-Cholewo et al. 2009)."}

{"project":"LitCovid-PD-CHEBI","denotations":[{"id":"T470","span":{"begin":240,"end":246},"obj":"Chemical"},{"id":"T471","span":{"begin":248,"end":251},"obj":"Chemical"},{"id":"T472","span":{"begin":257,"end":265},"obj":"Chemical"},{"id":"T473","span":{"begin":267,"end":270},"obj":"Chemical"},{"id":"T475","span":{"begin":330,"end":339},"obj":"Chemical"},{"id":"T477","span":{"begin":364,"end":367},"obj":"Chemical"},{"id":"T479","span":{"begin":451,"end":460},"obj":"Chemical"},{"id":"T481","span":{"begin":505,"end":512},"obj":"Chemical"},{"id":"T482","span":{"begin":513,"end":522},"obj":"Chemical"},{"id":"T484","span":{"begin":662,"end":670},"obj":"Chemical"},{"id":"T486","span":{"begin":809,"end":829},"obj":"Chemical"},{"id":"T487","span":{"begin":820,"end":829},"obj":"Chemical"},{"id":"T488","span":{"begin":860,"end":868},"obj":"Chemical"},{"id":"T490","span":{"begin":928,"end":930},"obj":"Chemical"},{"id":"T492","span":{"begin":989,"end":992},"obj":"Chemical"},{"id":"T493","span":{"begin":996,"end":999},"obj":"Chemical"},{"id":"T495","span":{"begin":1349,"end":1352},"obj":"Chemical"},{"id":"T496","span":{"begin":1408,"end":1416},"obj":"Chemical"},{"id":"T498","span":{"begin":1601,"end":1603},"obj":"Chemical"}],"attributes":[{"id":"A470","pred":"chebi_id","subj":"T470","obj":"http://purl.obolibrary.org/obo/CHEBI_25805"},{"id":"A471","pred":"chebi_id","subj":"T471","obj":"http://purl.obolibrary.org/obo/CHEBI_26523"},{"id":"A472","pred":"chebi_id","subj":"T472","obj":"http://purl.obolibrary.org/obo/CHEBI_25555"},{"id":"A473","pred":"chebi_id","subj":"T473","obj":"http://purl.obolibrary.org/obo/CHEBI_33697"},{"id":"A474","pred":"chebi_id","subj":"T473","obj":"http://purl.obolibrary.org/obo/CHEBI_62764"},{"id":"A475","pred":"chebi_id","subj":"T475","obj":"http://purl.obolibrary.org/obo/CHEBI_14321"},{"id":"A476","pred":"chebi_id","subj":"T475","obj":"http://purl.obolibrary.org/obo/CHEBI_29987"},{"id":"A477","pred":"chebi_id","subj":"T477","obj":"http://purl.obolibrary.org/obo/CHEBI_15422"},{"id":"A478","pred":"chebi_id","subj":"T477","obj":"http://purl.obolibrary.org/obo/CHEBI_30616"},{"id":"A479","pred":"chebi_id","subj":"T479","obj":"http://purl.obolibrary.org/obo/CHEBI_14321"},{"id":"A480","pred":"chebi_id","subj":"T479","obj":"http://purl.obolibrary.org/obo/CHEBI_29987"},{"id":"A481","pred":"chebi_id","subj":"T481","obj":"http://purl.obolibrary.org/obo/CHEBI_17376"},{"id":"A482","pred":"chebi_id","subj":"T482","obj":"http://purl.obolibrary.org/obo/CHEBI_14321"},{"id":"A483","pred":"chebi_id","subj":"T482","obj":"http://purl.obolibrary.org/obo/CHEBI_29987"},{"id":"A484","pred":"chebi_id","subj":"T484","obj":"http://purl.obolibrary.org/obo/CHEBI_17303"},{"id":"A485","pred":"chebi_id","subj":"T484","obj":"http://purl.obolibrary.org/obo/CHEBI_58097"},{"id":"A486","pred":"chebi_id","subj":"T486","obj":"http://purl.obolibrary.org/obo/CHEBI_52726"},{"id":"A487","pred":"chebi_id","subj":"T487","obj":"http://purl.obolibrary.org/obo/CHEBI_35222"},{"id":"A488","pred":"chebi_id","subj":"T488","obj":"http://purl.obolibrary.org/obo/CHEBI_17303"},{"id":"A489","pred":"chebi_id","subj":"T488","obj":"http://purl.obolibrary.org/obo/CHEBI_58097"},{"id":"A490","pred":"chebi_id","subj":"T490","obj":"http://purl.obolibrary.org/obo/CHEBI_63895"},{"id":"A491","pred":"chebi_id","subj":"T490","obj":"http://purl.obolibrary.org/obo/CHEBI_74072"},{"id":"A492","pred":"chebi_id","subj":"T492","obj":"http://purl.obolibrary.org/obo/CHEBI_26523"},{"id":"A493","pred":"chebi_id","subj":"T493","obj":"http://purl.obolibrary.org/obo/CHEBI_33697"},{"id":"A494","pred":"chebi_id","subj":"T493","obj":"http://purl.obolibrary.org/obo/CHEBI_62764"},{"id":"A495","pred":"chebi_id","subj":"T495","obj":"http://purl.obolibrary.org/obo/CHEBI_26523"},{"id":"A496","pred":"chebi_id","subj":"T496","obj":"http://purl.obolibrary.org/obo/CHEBI_17303"},{"id":"A497","pred":"chebi_id","subj":"T496","obj":"http://purl.obolibrary.org/obo/CHEBI_58097"},{"id":"A498","pred":"chebi_id","subj":"T498","obj":"http://purl.obolibrary.org/obo/CHEBI_141424"},{"id":"A499","pred":"chebi_id","subj":"T498","obj":"http://purl.obolibrary.org/obo/CHEBI_25573"},{"id":"A500","pred":"chebi_id","subj":"T498","obj":"http://purl.obolibrary.org/obo/CHEBI_1224"}],"text":"Unlike in astrocytes, opiate and HIV interactions in microglia tend to be self-limiting (Turchan-Cholewo et al. 2009). Opiates initially trigger large increases in the production of proinflammatory cytokines (Hauser, unpublished), reactive oxygen (ROS) and nitrogen (RNS) species (Turchan-Cholewo et al. 2009), and the release of glutamate (Gupta et al. 2010) and ATP (Sorrell and Hauser 2014) extracellularly in Tat-exposed microglia. The release of glutamate is mediated by the catalytic subunit of the cystine-glutamate antiporter xc− (xCT) (Gupta et al. 2010). Interestingly, following acute increases in the release of cytokines (e.g., TNF-α; unpublished), morphine no longer increases Tat-induced cytokine levels at 24 h; instead, their levels are reduced by opiate-dependent proteasome inhibition. The proteasome inhibitor, MG115, mimics the effects of morphine in decreasing proteasome activity at 24 h and blocks TNFα, IL-6, and CCL2 release from microglia, but does not increase ROS or RNS production (Turchan-Cholewo et al. 2009). The ubiquitin proteasome system (UPS) is typically viewed as contributing to opiate tolerance and physical dependence by modulating MOR downregulation (Massaly et al. 2014; Caputi et al. 2019), rather than MOR activity constraining the UPS. Thus, while HIV-exposed, MOR-expressing microglia show a burst of ROS and proinflammatory cytokine production in response to morphine, the cytokine release collapses within 24 h seemingly because sustained opiate exposure inhibits the UPS thereby preventing degradation of the IκB subunit and nuclear translocation of NF-κB (Turchan-Cholewo et al. 2009)."}

{"project":"LitCovid-PubTator","denotations":[{"id":"1760","span":{"begin":413,"end":416},"obj":"Gene"},{"id":"1761","span":{"begin":539,"end":542},"obj":"Gene"},{"id":"1762","span":{"begin":641,"end":646},"obj":"Gene"},{"id":"1763","span":{"begin":691,"end":694},"obj":"Gene"},{"id":"1764","span":{"begin":922,"end":926},"obj":"Gene"},{"id":"1765","span":{"begin":928,"end":932},"obj":"Gene"},{"id":"1766","span":{"begin":938,"end":942},"obj":"Gene"},{"id":"1767","span":{"begin":1174,"end":1177},"obj":"Gene"},{"id":"1768","span":{"begin":1248,"end":1251},"obj":"Gene"},{"id":"1769","span":{"begin":1308,"end":1311},"obj":"Gene"},{"id":"1770","span":{"begin":1601,"end":1606},"obj":"Gene"},{"id":"1771","span":{"begin":33,"end":36},"obj":"Species"},{"id":"1772","span":{"begin":1295,"end":1298},"obj":"Species"},{"id":"1773","span":{"begin":231,"end":246},"obj":"Chemical"},{"id":"1774","span":{"begin":248,"end":251},"obj":"Chemical"},{"id":"1775","span":{"begin":257,"end":265},"obj":"Chemical"},{"id":"1776","span":{"begin":267,"end":270},"obj":"Chemical"},{"id":"1777","span":{"begin":330,"end":339},"obj":"Chemical"},{"id":"1778","span":{"begin":364,"end":367},"obj":"Chemical"},{"id":"1779","span":{"begin":451,"end":460},"obj":"Chemical"},{"id":"1780","span":{"begin":505,"end":512},"obj":"Chemical"},{"id":"1781","span":{"begin":513,"end":522},"obj":"Chemical"},{"id":"1782","span":{"begin":662,"end":670},"obj":"Chemical"},{"id":"1783","span":{"begin":831,"end":836},"obj":"Chemical"},{"id":"1784","span":{"begin":860,"end":868},"obj":"Chemical"},{"id":"1785","span":{"begin":989,"end":992},"obj":"Chemical"},{"id":"1786","span":{"begin":996,"end":999},"obj":"Chemical"},{"id":"1787","span":{"begin":1408,"end":1416},"obj":"Chemical"}],"attributes":[{"id":"A1760","pred":"tao:has_database_id","subj":"1760","obj":"Gene:6898"},{"id":"A1761","pred":"tao:has_database_id","subj":"1761","obj":"Gene:23657"},{"id":"A1762","pred":"tao:has_database_id","subj":"1762","obj":"Gene:7124"},{"id":"A1763","pred":"tao:has_database_id","subj":"1763","obj":"Gene:6898"},{"id":"A1764","pred":"tao:has_database_id","subj":"1764","obj":"Gene:7124"},{"id":"A1765","pred":"tao:has_database_id","subj":"1765","obj":"Gene:3569"},{"id":"A1766","pred":"tao:has_database_id","subj":"1766","obj":"Gene:6347"},{"id":"A1767","pred":"tao:has_database_id","subj":"1767","obj":"Gene:4988"},{"id":"A1768","pred":"tao:has_database_id","subj":"1768","obj":"Gene:4988"},{"id":"A1769","pred":"tao:has_database_id","subj":"1769","obj":"Gene:4988"},{"id":"A1770","pred":"tao:has_database_id","subj":"1770","obj":"Gene:4790"},{"id":"A1771","pred":"tao:has_database_id","subj":"1771","obj":"Tax:12721"},{"id":"A1772","pred":"tao:has_database_id","subj":"1772","obj":"Tax:12721"},{"id":"A1775","pred":"tao:has_database_id","subj":"1775","obj":"MESH:D009584"},{"id":"A1776","pred":"tao:has_database_id","subj":"1776","obj":"MESH:D026361"},{"id":"A1777","pred":"tao:has_database_id","subj":"1777","obj":"MESH:D018698"},{"id":"A1778","pred":"tao:has_database_id","subj":"1778","obj":"MESH:D000255"},{"id":"A1779","pred":"tao:has_database_id","subj":"1779","obj":"MESH:D018698"},{"id":"A1780","pred":"tao:has_database_id","subj":"1780","obj":"MESH:D003553"},{"id":"A1781","pred":"tao:has_database_id","subj":"1781","obj":"MESH:D018698"},{"id":"A1782","pred":"tao:has_database_id","subj":"1782","obj":"MESH:D009020"},{"id":"A1783","pred":"tao:has_database_id","subj":"1783","obj":"MESH:C089486"},{"id":"A1784","pred":"tao:has_database_id","subj":"1784","obj":"MESH:D009020"},{"id":"A1786","pred":"tao:has_database_id","subj":"1786","obj":"MESH:D026361"},{"id":"A1787","pred":"tao:has_database_id","subj":"1787","obj":"MESH:D009020"}],"namespaces":[{"prefix":"Tax","uri":"https://www.ncbi.nlm.nih.gov/taxonomy/"},{"prefix":"MESH","uri":"https://id.nlm.nih.gov/mesh/"},{"prefix":"Gene","uri":"https://www.ncbi.nlm.nih.gov/gene/"},{"prefix":"CVCL","uri":"https://web.expasy.org/cellosaurus/CVCL_"}],"text":"Unlike in astrocytes, opiate and HIV interactions in microglia tend to be self-limiting (Turchan-Cholewo et al. 2009). Opiates initially trigger large increases in the production of proinflammatory cytokines (Hauser, unpublished), reactive oxygen (ROS) and nitrogen (RNS) species (Turchan-Cholewo et al. 2009), and the release of glutamate (Gupta et al. 2010) and ATP (Sorrell and Hauser 2014) extracellularly in Tat-exposed microglia. The release of glutamate is mediated by the catalytic subunit of the cystine-glutamate antiporter xc− (xCT) (Gupta et al. 2010). Interestingly, following acute increases in the release of cytokines (e.g., TNF-α; unpublished), morphine no longer increases Tat-induced cytokine levels at 24 h; instead, their levels are reduced by opiate-dependent proteasome inhibition. The proteasome inhibitor, MG115, mimics the effects of morphine in decreasing proteasome activity at 24 h and blocks TNFα, IL-6, and CCL2 release from microglia, but does not increase ROS or RNS production (Turchan-Cholewo et al. 2009). The ubiquitin proteasome system (UPS) is typically viewed as contributing to opiate tolerance and physical dependence by modulating MOR downregulation (Massaly et al. 2014; Caputi et al. 2019), rather than MOR activity constraining the UPS. Thus, while HIV-exposed, MOR-expressing microglia show a burst of ROS and proinflammatory cytokine production in response to morphine, the cytokine release collapses within 24 h seemingly because sustained opiate exposure inhibits the UPS thereby preventing degradation of the IκB subunit and nuclear translocation of NF-κB (Turchan-Cholewo et al. 2009)."}

{"project":"LitCovid-PD-GO-BP","denotations":[{"id":"T81","span":{"begin":1373,"end":1392},"obj":"http://purl.obolibrary.org/obo/GO_0001816"},{"id":"T82","span":{"begin":1396,"end":1416},"obj":"http://purl.obolibrary.org/obo/GO_0043278"},{"id":"T83","span":{"begin":1541,"end":1552},"obj":"http://purl.obolibrary.org/obo/GO_0009056"}],"text":"Unlike in astrocytes, opiate and HIV interactions in microglia tend to be self-limiting (Turchan-Cholewo et al. 2009). Opiates initially trigger large increases in the production of proinflammatory cytokines (Hauser, unpublished), reactive oxygen (ROS) and nitrogen (RNS) species (Turchan-Cholewo et al. 2009), and the release of glutamate (Gupta et al. 2010) and ATP (Sorrell and Hauser 2014) extracellularly in Tat-exposed microglia. The release of glutamate is mediated by the catalytic subunit of the cystine-glutamate antiporter xc− (xCT) (Gupta et al. 2010). Interestingly, following acute increases in the release of cytokines (e.g., TNF-α; unpublished), morphine no longer increases Tat-induced cytokine levels at 24 h; instead, their levels are reduced by opiate-dependent proteasome inhibition. The proteasome inhibitor, MG115, mimics the effects of morphine in decreasing proteasome activity at 24 h and blocks TNFα, IL-6, and CCL2 release from microglia, but does not increase ROS or RNS production (Turchan-Cholewo et al. 2009). The ubiquitin proteasome system (UPS) is typically viewed as contributing to opiate tolerance and physical dependence by modulating MOR downregulation (Massaly et al. 2014; Caputi et al. 2019), rather than MOR activity constraining the UPS. Thus, while HIV-exposed, MOR-expressing microglia show a burst of ROS and proinflammatory cytokine production in response to morphine, the cytokine release collapses within 24 h seemingly because sustained opiate exposure inhibits the UPS thereby preventing degradation of the IκB subunit and nuclear translocation of NF-κB (Turchan-Cholewo et al. 2009)."}

{"project":"LitCovid-sentences","denotations":[{"id":"T699","span":{"begin":0,"end":111},"obj":"Sentence"},{"id":"T700","span":{"begin":112,"end":118},"obj":"Sentence"},{"id":"T701","span":{"begin":119,"end":303},"obj":"Sentence"},{"id":"T702","span":{"begin":304,"end":353},"obj":"Sentence"},{"id":"T703","span":{"begin":354,"end":435},"obj":"Sentence"},{"id":"T704","span":{"begin":436,"end":557},"obj":"Sentence"},{"id":"T705","span":{"begin":558,"end":564},"obj":"Sentence"},{"id":"T706","span":{"begin":565,"end":804},"obj":"Sentence"},{"id":"T707","span":{"begin":805,"end":1034},"obj":"Sentence"},{"id":"T708","span":{"begin":1035,"end":1041},"obj":"Sentence"},{"id":"T709","span":{"begin":1042,"end":1208},"obj":"Sentence"},{"id":"T710","span":{"begin":1209,"end":1228},"obj":"Sentence"},{"id":"T711","span":{"begin":1229,"end":1282},"obj":"Sentence"},{"id":"T712","span":{"begin":1283,"end":1630},"obj":"Sentence"},{"id":"T713","span":{"begin":1631,"end":1637},"obj":"Sentence"}],"namespaces":[{"prefix":"_base","uri":"http://pubannotation.org/ontology/tao.owl#"}],"text":"Unlike in astrocytes, opiate and HIV interactions in microglia tend to be self-limiting (Turchan-Cholewo et al. 2009). Opiates initially trigger large increases in the production of proinflammatory cytokines (Hauser, unpublished), reactive oxygen (ROS) and nitrogen (RNS) species (Turchan-Cholewo et al. 2009), and the release of glutamate (Gupta et al. 2010) and ATP (Sorrell and Hauser 2014) extracellularly in Tat-exposed microglia. The release of glutamate is mediated by the catalytic subunit of the cystine-glutamate antiporter xc− (xCT) (Gupta et al. 2010). Interestingly, following acute increases in the release of cytokines (e.g., TNF-α; unpublished), morphine no longer increases Tat-induced cytokine levels at 24 h; instead, their levels are reduced by opiate-dependent proteasome inhibition. The proteasome inhibitor, MG115, mimics the effects of morphine in decreasing proteasome activity at 24 h and blocks TNFα, IL-6, and CCL2 release from microglia, but does not increase ROS or RNS production (Turchan-Cholewo et al. 2009). The ubiquitin proteasome system (UPS) is typically viewed as contributing to opiate tolerance and physical dependence by modulating MOR downregulation (Massaly et al. 2014; Caputi et al. 2019), rather than MOR activity constraining the UPS. Thus, while HIV-exposed, MOR-expressing microglia show a burst of ROS and proinflammatory cytokine production in response to morphine, the cytokine release collapses within 24 h seemingly because sustained opiate exposure inhibits the UPS thereby preventing degradation of the IκB subunit and nuclear translocation of NF-κB (Turchan-Cholewo et al. 2009)."}

{"project":"2_test","denotations":[{"id":"32876803-24158495-62958097","span":{"begin":388,"end":392},"obj":"24158495"},{"id":"32876803-25610367-62958098","span":{"begin":1209,"end":1213},"obj":"25610367"}],"text":"Unlike in astrocytes, opiate and HIV interactions in microglia tend to be self-limiting (Turchan-Cholewo et al. 2009). Opiates initially trigger large increases in the production of proinflammatory cytokines (Hauser, unpublished), reactive oxygen (ROS) and nitrogen (RNS) species (Turchan-Cholewo et al. 2009), and the release of glutamate (Gupta et al. 2010) and ATP (Sorrell and Hauser 2014) extracellularly in Tat-exposed microglia. The release of glutamate is mediated by the catalytic subunit of the cystine-glutamate antiporter xc− (xCT) (Gupta et al. 2010). Interestingly, following acute increases in the release of cytokines (e.g., TNF-α; unpublished), morphine no longer increases Tat-induced cytokine levels at 24 h; instead, their levels are reduced by opiate-dependent proteasome inhibition. The proteasome inhibitor, MG115, mimics the effects of morphine in decreasing proteasome activity at 24 h and blocks TNFα, IL-6, and CCL2 release from microglia, but does not increase ROS or RNS production (Turchan-Cholewo et al. 2009). The ubiquitin proteasome system (UPS) is typically viewed as contributing to opiate tolerance and physical dependence by modulating MOR downregulation (Massaly et al. 2014; Caputi et al. 2019), rather than MOR activity constraining the UPS. Thus, while HIV-exposed, MOR-expressing microglia show a burst of ROS and proinflammatory cytokine production in response to morphine, the cytokine release collapses within 24 h seemingly because sustained opiate exposure inhibits the UPS thereby preventing degradation of the IκB subunit and nuclear translocation of NF-κB (Turchan-Cholewo et al. 2009)."}