PMC:7573190 / 3560-6535
Annnotations
MyTest
{"project":"MyTest","denotations":[{"id":"33088259-7611675-29829675","span":{"begin":107,"end":108},"obj":"7611675"},{"id":"33088259-28804022-29829676","span":{"begin":135,"end":137},"obj":"28804022"},{"id":"33088259-7510950-29829677","span":{"begin":324,"end":326},"obj":"7510950"},{"id":"33088259-9702990-29829678","span":{"begin":342,"end":344},"obj":"9702990"},{"id":"33088259-11017941-29829679","span":{"begin":365,"end":368},"obj":"11017941"},{"id":"33088259-24878261-29829680","span":{"begin":395,"end":398},"obj":"24878261"},{"id":"33088259-15465779-29829681","span":{"begin":603,"end":606},"obj":"15465779"},{"id":"33088259-8858108-29829682","span":{"begin":826,"end":828},"obj":"8858108"},{"id":"33088259-17459909-29829683","span":{"begin":853,"end":855},"obj":"17459909"},{"id":"33088259-12482944-29829684","span":{"begin":1013,"end":1015},"obj":"12482944"},{"id":"33088259-12824867-29829685","span":{"begin":1038,"end":1041},"obj":"12824867"},{"id":"33088259-12655043-29829686","span":{"begin":1206,"end":1208},"obj":"12655043"},{"id":"33088259-19841582-29829687","span":{"begin":1232,"end":1234},"obj":"19841582"},{"id":"33088259-19546350-29829688","span":{"begin":1325,"end":1327},"obj":"19546350"},{"id":"33088259-21890489-29829689","span":{"begin":1599,"end":1601},"obj":"21890489"},{"id":"33088259-21890489-29829690","span":{"begin":1762,"end":1764},"obj":"21890489"},{"id":"33088259-9218522-29829691","span":{"begin":1953,"end":1956},"obj":"9218522"},{"id":"33088259-24878261-29829692","span":{"begin":1983,"end":1986},"obj":"24878261"},{"id":"33088259-9218522-29829693","span":{"begin":2104,"end":2107},"obj":"9218522"},{"id":"33088259-22267589-29829694","span":{"begin":2291,"end":2293},"obj":"22267589"},{"id":"33088259-18167491-29829695","span":{"begin":2457,"end":2459},"obj":"18167491"},{"id":"33088259-20876122-29829696","span":{"begin":2571,"end":2573},"obj":"20876122"},{"id":"33088259-21619929-29829697","span":{"begin":2595,"end":2597},"obj":"21619929"},{"id":"33088259-9706737-29829698","span":{"begin":2732,"end":2735},"obj":"9706737"},{"id":"33088259-18167491-29829699","span":{"begin":2936,"end":2938},"obj":"18167491"},{"id":"33088259-19919855-29829700","span":{"begin":2970,"end":2972},"obj":"19919855"}],"namespaces":[{"prefix":"_base","uri":"https://www.uniprot.org/uniprot/testbase"},{"prefix":"UniProtKB","uri":"https://www.uniprot.org/uniprot/"},{"prefix":"uniprot","uri":"https://www.uniprot.org/uniprotkb/"}],"text":"Production of NO\nNitric oxide is produced in NOS-dependent and independent pathways (Aronstam et al., 1995[6]; Ghasemi and Jeddi, 2017[39]). In NOS-dependent pathways, NO is produced by three isoforms of NOS, referred to as neuronal (nNOS/NOS1), inducible (iNOS/NOS2), and endothelial (eNOS/NOS3) (Knowles and Moncada, 1994[64]; Cannon, 1998[17]; Yoon et al., 2000[138]; Sansbury and Hill, 2014[109]). L-arginine is the substrate for all isoforms. For NO generation, NOS first hydroxylates L-arginine to N(omega)-hydroxy-L-arginine (L-NOHA) and then oxidizes L-NOHA to L-citrulline and NO (Stuehr, 2004[122]).\nBoth nNOS and eNOS are constitutively expressed proteins, collectively termed as cNOS; nNOS is expressed in specific neurons of the brain but also found in skeletal muscle and epithelial cells (Frandsen et al., 1996[34]; McConell et al., 2007[85]). eNOS, which produces relatively low quantities of NO, is expressed at the highest relative abundance in the vascular endothelium (McNaughton et al., 2002[88]; Tanaka et al., 2003[125]). Although iNOS expression is primarily identified in macrophages, it can be induced in virtually any cells or tissues by inflammatory cytokines (Lee et al., 2003[72]; Luiking et al., 2010[76]). A mitochondria-localized NOS isoform has also been reported (Finocchietto et al., 2009[32]), however, its specific contribution remains unclear. Activity of cNOS is regulated by Ca2+ and calmodulin; by elevation in intracellular Ca2+ levels, eNOS activity is markedly increased and results in production of NO in a pulsatile manner (Forstermann and Sessa, 2012[33]). Activity of iNOS is not regulated by Ca2+ with calmodulin and the enzyme active even at extremely low intracellular Ca2+ levels (Forstermann and Sessa, 2012[33]; Berridge, 2014[13]). Once expressed, iNOS produces a large amount of NO. Higher concentrations of NO, produced by iNOS or exogenous NO leads to inhibition of cNOS (Schwartz et al., 1997[111]; Sansbury and Hill, 2014[109]), as lower concentrations of NO are required for inhibition of cNOS than for iNOS inhibition (Schwartz et al., 1997[111]).\nIn NOS-independent pathways, NO is produced from nitrate and nitrite; oxidation of endogenous NO and diet are two major sources of nitrate in mammals (Lundberg and Weitzberg, 2013[78]). About 25 % of circulating nitrate is actively taken up by the salivary glands and then reduced to nitrite by the oral commensal bacteria (Lundberg et al., 2008[80]). After oral loading, nitrate/nitrite is rapidly absorbed in the duodenum and jejunum (Carlstrom et al., 2010[18]; Kevil et al., 2011[63]). In the stomach, part of the nitrite is reduced to NO but most of it is absorbed into the circulation (Weitzberg and Lundberg, 1998[131]; Dauncey, 2012[25]). Nitrite reduction to NO in blood and tissues could be enzymatic or non-enzymatic and is generally enhanced during hypoxic, ischemic, and acidic conditions (Lundberg et al., 2008[80]; Lundberg and Weitzberg, 2010[79])."}
2_test
{"project":"2_test","denotations":[{"id":"33088259-7611675-29829675","span":{"begin":107,"end":108},"obj":"7611675"},{"id":"33088259-28804022-29829676","span":{"begin":135,"end":137},"obj":"28804022"},{"id":"33088259-7510950-29829677","span":{"begin":324,"end":326},"obj":"7510950"},{"id":"33088259-9702990-29829678","span":{"begin":342,"end":344},"obj":"9702990"},{"id":"33088259-11017941-29829679","span":{"begin":365,"end":368},"obj":"11017941"},{"id":"33088259-24878261-29829680","span":{"begin":395,"end":398},"obj":"24878261"},{"id":"33088259-15465779-29829681","span":{"begin":603,"end":606},"obj":"15465779"},{"id":"33088259-8858108-29829682","span":{"begin":826,"end":828},"obj":"8858108"},{"id":"33088259-17459909-29829683","span":{"begin":853,"end":855},"obj":"17459909"},{"id":"33088259-12482944-29829684","span":{"begin":1013,"end":1015},"obj":"12482944"},{"id":"33088259-12824867-29829685","span":{"begin":1038,"end":1041},"obj":"12824867"},{"id":"33088259-12655043-29829686","span":{"begin":1206,"end":1208},"obj":"12655043"},{"id":"33088259-19841582-29829687","span":{"begin":1232,"end":1234},"obj":"19841582"},{"id":"33088259-19546350-29829688","span":{"begin":1325,"end":1327},"obj":"19546350"},{"id":"33088259-21890489-29829689","span":{"begin":1599,"end":1601},"obj":"21890489"},{"id":"33088259-21890489-29829690","span":{"begin":1762,"end":1764},"obj":"21890489"},{"id":"33088259-9218522-29829691","span":{"begin":1953,"end":1956},"obj":"9218522"},{"id":"33088259-24878261-29829692","span":{"begin":1983,"end":1986},"obj":"24878261"},{"id":"33088259-9218522-29829693","span":{"begin":2104,"end":2107},"obj":"9218522"},{"id":"33088259-22267589-29829694","span":{"begin":2291,"end":2293},"obj":"22267589"},{"id":"33088259-18167491-29829695","span":{"begin":2457,"end":2459},"obj":"18167491"},{"id":"33088259-20876122-29829696","span":{"begin":2571,"end":2573},"obj":"20876122"},{"id":"33088259-21619929-29829697","span":{"begin":2595,"end":2597},"obj":"21619929"},{"id":"33088259-9706737-29829698","span":{"begin":2732,"end":2735},"obj":"9706737"},{"id":"33088259-18167491-29829699","span":{"begin":2936,"end":2938},"obj":"18167491"},{"id":"33088259-19919855-29829700","span":{"begin":2970,"end":2972},"obj":"19919855"}],"text":"Production of NO\nNitric oxide is produced in NOS-dependent and independent pathways (Aronstam et al., 1995[6]; Ghasemi and Jeddi, 2017[39]). In NOS-dependent pathways, NO is produced by three isoforms of NOS, referred to as neuronal (nNOS/NOS1), inducible (iNOS/NOS2), and endothelial (eNOS/NOS3) (Knowles and Moncada, 1994[64]; Cannon, 1998[17]; Yoon et al., 2000[138]; Sansbury and Hill, 2014[109]). L-arginine is the substrate for all isoforms. For NO generation, NOS first hydroxylates L-arginine to N(omega)-hydroxy-L-arginine (L-NOHA) and then oxidizes L-NOHA to L-citrulline and NO (Stuehr, 2004[122]).\nBoth nNOS and eNOS are constitutively expressed proteins, collectively termed as cNOS; nNOS is expressed in specific neurons of the brain but also found in skeletal muscle and epithelial cells (Frandsen et al., 1996[34]; McConell et al., 2007[85]). eNOS, which produces relatively low quantities of NO, is expressed at the highest relative abundance in the vascular endothelium (McNaughton et al., 2002[88]; Tanaka et al., 2003[125]). Although iNOS expression is primarily identified in macrophages, it can be induced in virtually any cells or tissues by inflammatory cytokines (Lee et al., 2003[72]; Luiking et al., 2010[76]). A mitochondria-localized NOS isoform has also been reported (Finocchietto et al., 2009[32]), however, its specific contribution remains unclear. Activity of cNOS is regulated by Ca2+ and calmodulin; by elevation in intracellular Ca2+ levels, eNOS activity is markedly increased and results in production of NO in a pulsatile manner (Forstermann and Sessa, 2012[33]). Activity of iNOS is not regulated by Ca2+ with calmodulin and the enzyme active even at extremely low intracellular Ca2+ levels (Forstermann and Sessa, 2012[33]; Berridge, 2014[13]). Once expressed, iNOS produces a large amount of NO. Higher concentrations of NO, produced by iNOS or exogenous NO leads to inhibition of cNOS (Schwartz et al., 1997[111]; Sansbury and Hill, 2014[109]), as lower concentrations of NO are required for inhibition of cNOS than for iNOS inhibition (Schwartz et al., 1997[111]).\nIn NOS-independent pathways, NO is produced from nitrate and nitrite; oxidation of endogenous NO and diet are two major sources of nitrate in mammals (Lundberg and Weitzberg, 2013[78]). About 25 % of circulating nitrate is actively taken up by the salivary glands and then reduced to nitrite by the oral commensal bacteria (Lundberg et al., 2008[80]). After oral loading, nitrate/nitrite is rapidly absorbed in the duodenum and jejunum (Carlstrom et al., 2010[18]; Kevil et al., 2011[63]). In the stomach, part of the nitrite is reduced to NO but most of it is absorbed into the circulation (Weitzberg and Lundberg, 1998[131]; Dauncey, 2012[25]). Nitrite reduction to NO in blood and tissues could be enzymatic or non-enzymatic and is generally enhanced during hypoxic, ischemic, and acidic conditions (Lundberg et al., 2008[80]; Lundberg and Weitzberg, 2010[79])."}