PubMed:17129494 JSONTXT

{"project":"PubmedHPO","denotations":[{"id":"T1","span":{"begin":330,"end":352},"obj":"HP_0002092"},{"id":"T2","span":{"begin":340,"end":352},"obj":"HP_0000822"}],"text":"[Reciprocal regulation between hypoxia-inducible factor-1alpha and its prolyl hydroxylases in hypoxic pulmonary hypertension rats].\nOBJECTIVE: To investigate the interaction between hypoxia-inducible factors-1alpha subunit (HIF-1alpha) and its three prolyl hydroxylases (PHD1, PHD2 and PHD3) during the development of rat hypoxic pulmonary hypertension.\nMETHODS: Forty male SD rats were randomly divided into 5 groups and exposed to normoxia (C group) or exposed to hypoxia for 3, 7, 14 or 21 d (H(3), H(7), H(14), H(21) group), respectively. Mean pulmonary arterial pressure (mPAP), vessel morphometry and right ventricle hypertrophy index (RVHI) were measured. Reverse transcriptase-polymerase chain reaction (RT-PCR) and in situ hybridization were used to determine the expression of mRNA. Immunohistochemistry and Western blot were used to determine the expression of mRNA.\nRESULTS: The level of mPAP [(21.7 +/- 2.4) mm Hg, 1 mm Hg = 0.133 kPa], the ratio of vascular wall thickness to external diameter [WA%, (43.9 +/- 5.3)%] and pulmonary artery media thickness [PAMT, (10.0 +/- 0.7) microm] were significantly higher in H(7) group than those in C group [(16.6 +/- 1.6) mm Hg, (36.3 +/- 4.8)% and (8.5 +/- 1.3) microm respectively, q value were 5.591, 4.082, 2.929, respectively, all P \u003c 0.05]. These parameters reached a high level and remained stable on H(14) group, and RVHI was significantly higher in H(14) group [(27.6 +/- 1.4)%] than in C group [(23.6 +/- 2.9)%, q = 5.817, P \u003c 0.05]. HIF-1alpha protein was barely positive in C group (0.080 +/- 0.009), but markedly up-regulated in H(3) group (0.196 +/- 0.018, compared with C group q = 18.864, P \u003c 0.05), reaching its peak in H(7) group (0.203 +/- 0.022), and then declined slightly in H(14) and H(21) group. HIF-1alpha mRNA increased marginally in H(14) group (0.176 +/- 0.019, compared with C group q = 5.401, P \u003c 0.05, 0.139 +/- 0.017). PHD1 and PHD2 mRNA (0.260 +/- 0.031, 0.196 +/- 0.023) and protein (0.244 +/- 0.030, 0.205 +/- 0.025) were positive in C group. PHD2 mRNA and protein were up-regulated in H(3) group (0.246 +/- 0.023, 0.235 +/- 0.025, compared with C group q value was 5.268, 3.046, respectively, all P \u003c 0.05), reaching its peak in H(14) group whereas PHD1 protein declined in H(14) group (0.210 +/- 0.023, compared with C group q = 3.885, P \u003c 0.05) without significant mRNA change. PHD3 mRNA and protein were detected at low level in C group (0.110 +/- 0.013, 0.153 +/- 0.019), but markedly up-regulated in H(3) group (0.259 +/- 0.024, compared with C group q = 15.831, P \u003c 0.05), and then PHD3 mRNA remained at high level while PHD3 protein declined in H(14) and H(21) group (0.206 +/- 0.025, 0.189 +/- 0.019, compared with H(7) group q value was 6.441, 8.526, respectively, all P \u003c 0.05). Linear correlation analysis showed that HIF-1alpha mRNA and protein were positively correlated with mPAP. There was a positive correlation between HIF-1alpha protein and PHD2, PHD3 mRNA (r value was 0.580, 0.690, respectively, all P value was 0.000) but a negative correlation between HIF-1alpha protein and PHD2 protein (r = -0.704, P \u003c 0.05).\nCONCLUSIONS: HIF-1alpha was regulated mainly at the protein level during the development of hypoxic pulmonary hypertension. PHD2 and PHD3 are inducible by hypoxia, possibly via elevated HIF-1alpha, suggesting that a hypoxic up-regulation of PHD acts via feedback mechanism to attenuate hypoxia induced responses. PHD may also be regulated by posttranscriptional mechanisms."}

{"project":"bionlp-st-epi-2011-training","denotations":[{"id":"T1","span":{"begin":31,"end":62},"obj":"Protein"},{"id":"T2","span":{"begin":182,"end":214},"obj":"Protein"},{"id":"T3","span":{"begin":224,"end":234},"obj":"Protein"},{"id":"T4","span":{"begin":271,"end":275},"obj":"Protein"},{"id":"T5","span":{"begin":277,"end":281},"obj":"Protein"},{"id":"T6","span":{"begin":286,"end":290},"obj":"Protein"},{"id":"T7","span":{"begin":663,"end":684},"obj":"Protein"},{"id":"T8","span":{"begin":1498,"end":1508},"obj":"Protein"},{"id":"T9","span":{"begin":1774,"end":1784},"obj":"Protein"},{"id":"T10","span":{"begin":1905,"end":1909},"obj":"Protein"},{"id":"T11","span":{"begin":1914,"end":1918},"obj":"Protein"},{"id":"T12","span":{"begin":2032,"end":2036},"obj":"Protein"},{"id":"T13","span":{"begin":2239,"end":2243},"obj":"Protein"},{"id":"T14","span":{"begin":2370,"end":2374},"obj":"Protein"},{"id":"T15","span":{"begin":2578,"end":2582},"obj":"Protein"},{"id":"T16","span":{"begin":2617,"end":2621},"obj":"Protein"},{"id":"T17","span":{"begin":2819,"end":2829},"obj":"Protein"},{"id":"T18","span":{"begin":2926,"end":2936},"obj":"Protein"},{"id":"T19","span":{"begin":2949,"end":2953},"obj":"Protein"},{"id":"T20","span":{"begin":2955,"end":2959},"obj":"Protein"},{"id":"T21","span":{"begin":3064,"end":3074},"obj":"Protein"},{"id":"T22","span":{"begin":3087,"end":3091},"obj":"Protein"},{"id":"T23","span":{"begin":3137,"end":3147},"obj":"Protein"},{"id":"T24","span":{"begin":3248,"end":3252},"obj":"Protein"},{"id":"T25","span":{"begin":3257,"end":3261},"obj":"Protein"},{"id":"T26","span":{"begin":3310,"end":3320},"obj":"Protein"}],"text":"[Reciprocal regulation between hypoxia-inducible factor-1alpha and its prolyl hydroxylases in hypoxic pulmonary hypertension rats].\nOBJECTIVE: To investigate the interaction between hypoxia-inducible factors-1alpha subunit (HIF-1alpha) and its three prolyl hydroxylases (PHD1, PHD2 and PHD3) during the development of rat hypoxic pulmonary hypertension.\nMETHODS: Forty male SD rats were randomly divided into 5 groups and exposed to normoxia (C group) or exposed to hypoxia for 3, 7, 14 or 21 d (H(3), H(7), H(14), H(21) group), respectively. Mean pulmonary arterial pressure (mPAP), vessel morphometry and right ventricle hypertrophy index (RVHI) were measured. Reverse transcriptase-polymerase chain reaction (RT-PCR) and in situ hybridization were used to determine the expression of mRNA. Immunohistochemistry and Western blot were used to determine the expression of mRNA.\nRESULTS: The level of mPAP [(21.7 +/- 2.4) mm Hg, 1 mm Hg = 0.133 kPa], the ratio of vascular wall thickness to external diameter [WA%, (43.9 +/- 5.3)%] and pulmonary artery media thickness [PAMT, (10.0 +/- 0.7) microm] were significantly higher in H(7) group than those in C group [(16.6 +/- 1.6) mm Hg, (36.3 +/- 4.8)% and (8.5 +/- 1.3) microm respectively, q value were 5.591, 4.082, 2.929, respectively, all P \u003c 0.05]. These parameters reached a high level and remained stable on H(14) group, and RVHI was significantly higher in H(14) group [(27.6 +/- 1.4)%] than in C group [(23.6 +/- 2.9)%, q = 5.817, P \u003c 0.05]. HIF-1alpha protein was barely positive in C group (0.080 +/- 0.009), but markedly up-regulated in H(3) group (0.196 +/- 0.018, compared with C group q = 18.864, P \u003c 0.05), reaching its peak in H(7) group (0.203 +/- 0.022), and then declined slightly in H(14) and H(21) group. HIF-1alpha mRNA increased marginally in H(14) group (0.176 +/- 0.019, compared with C group q = 5.401, P \u003c 0.05, 0.139 +/- 0.017). PHD1 and PHD2 mRNA (0.260 +/- 0.031, 0.196 +/- 0.023) and protein (0.244 +/- 0.030, 0.205 +/- 0.025) were positive in C group. PHD2 mRNA and protein were up-regulated in H(3) group (0.246 +/- 0.023, 0.235 +/- 0.025, compared with C group q value was 5.268, 3.046, respectively, all P \u003c 0.05), reaching its peak in H(14) group whereas PHD1 protein declined in H(14) group (0.210 +/- 0.023, compared with C group q = 3.885, P \u003c 0.05) without significant mRNA change. PHD3 mRNA and protein were detected at low level in C group (0.110 +/- 0.013, 0.153 +/- 0.019), but markedly up-regulated in H(3) group (0.259 +/- 0.024, compared with C group q = 15.831, P \u003c 0.05), and then PHD3 mRNA remained at high level while PHD3 protein declined in H(14) and H(21) group (0.206 +/- 0.025, 0.189 +/- 0.019, compared with H(7) group q value was 6.441, 8.526, respectively, all P \u003c 0.05). Linear correlation analysis showed that HIF-1alpha mRNA and protein were positively correlated with mPAP. There was a positive correlation between HIF-1alpha protein and PHD2, PHD3 mRNA (r value was 0.580, 0.690, respectively, all P value was 0.000) but a negative correlation between HIF-1alpha protein and PHD2 protein (r = -0.704, P \u003c 0.05).\nCONCLUSIONS: HIF-1alpha was regulated mainly at the protein level during the development of hypoxic pulmonary hypertension. PHD2 and PHD3 are inducible by hypoxia, possibly via elevated HIF-1alpha, suggesting that a hypoxic up-regulation of PHD acts via feedback mechanism to attenuate hypoxia induced responses. PHD may also be regulated by posttranscriptional mechanisms."}