PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 9220344-5 1997 Activation of NO formation by cytokines in cardiac myocytes requires transcriptional induction of the genes that encode iNOS and guanosine triphosphate cyclohydrolase I (GTPCH), the first and rate-limiting enzyme in de novo BH4 synthesis. sapropterin 224-227 nitric oxide synthase 2 Rattus norvegicus 120-124 9046035-6 1997 Our results demonstrate induction of NO synthesis and parallel increase in BH4 concentration in the heart of rats after LPS treatment in vivo and may provide molecular evidence responsible for the increased production of BH4 which may up-regulate iNOS activity in the heart in vivo. sapropterin 221-224 nitric oxide synthase 2 Rattus norvegicus 247-251 8798714-1 1996 Tetrahydrobiopterin (BH4) is an important cofactor for two hepatic enzymes, inducible nitric oxide synthase (iNOS) and phenylalanine hydroxylase (PAH), and competition for BH4 between the two enzymes might limit hepatic iNOS or PAH activity. sapropterin 0-19 nitric oxide synthase 2 Rattus norvegicus 76-107 8798714-1 1996 Tetrahydrobiopterin (BH4) is an important cofactor for two hepatic enzymes, inducible nitric oxide synthase (iNOS) and phenylalanine hydroxylase (PAH), and competition for BH4 between the two enzymes might limit hepatic iNOS or PAH activity. sapropterin 0-19 nitric oxide synthase 2 Rattus norvegicus 109-113 8798714-1 1996 Tetrahydrobiopterin (BH4) is an important cofactor for two hepatic enzymes, inducible nitric oxide synthase (iNOS) and phenylalanine hydroxylase (PAH), and competition for BH4 between the two enzymes might limit hepatic iNOS or PAH activity. sapropterin 0-19 nitric oxide synthase 2 Rattus norvegicus 220-224 8798714-1 1996 Tetrahydrobiopterin (BH4) is an important cofactor for two hepatic enzymes, inducible nitric oxide synthase (iNOS) and phenylalanine hydroxylase (PAH), and competition for BH4 between the two enzymes might limit hepatic iNOS or PAH activity. sapropterin 21-24 nitric oxide synthase 2 Rattus norvegicus 76-107 8798714-1 1996 Tetrahydrobiopterin (BH4) is an important cofactor for two hepatic enzymes, inducible nitric oxide synthase (iNOS) and phenylalanine hydroxylase (PAH), and competition for BH4 between the two enzymes might limit hepatic iNOS or PAH activity. sapropterin 21-24 nitric oxide synthase 2 Rattus norvegicus 109-113 8798714-1 1996 Tetrahydrobiopterin (BH4) is an important cofactor for two hepatic enzymes, inducible nitric oxide synthase (iNOS) and phenylalanine hydroxylase (PAH), and competition for BH4 between the two enzymes might limit hepatic iNOS or PAH activity. sapropterin 21-24 nitric oxide synthase 2 Rattus norvegicus 220-224 8798714-6 1996 Thus, basal BH4 synthesis appears to be adequate to support iNOS activity, whereas BH4 synthesis is increased to support PAH activity. sapropterin 12-15 nitric oxide synthase 2 Rattus norvegicus 60-64 33867911-6 2021 Furthermore, intrathecal injection of BH4 not only aggravated stress-induced hyperalgesia but also up-regulated the expression of spinal iNOS (iNOS mRNA: P = 0.015; iNOS protein: P < 0.001) and NO production (P < 0.001). sapropterin 38-41 nitric oxide synthase 2 Rattus norvegicus 137-141 8602831-7 1996 The results show that inhibition of tetrahydrobiopterin synthesis is an effective strategy to reduce nitric oxide synthesis by iNOS in vivo. sapropterin 36-55 nitric oxide synthase 2 Rattus norvegicus 127-131 7582541-4 1995 We have investigated the effects of an inhibitor of BH4 synthesis, N-acetyl-5-hydroxytryptamine (N-acetylserotonin, NAS), on the expression of iNOS in cultured macrophages and smooth muscle cells in vitro, and on the hypotensive response to bacterial lipopolysaccharide (LPS) in the anaesthetized rat in vivo. sapropterin 52-55 nitric oxide synthase 2 Rattus norvegicus 143-147 7802762-6 1994 In the current study we extend observations on regulation of iNOS in RPASM by showing that de novo synthesis of tetrahydrobiopterin (BH4) is critical for LPS and cytokine-induced NO production. sapropterin 112-131 nitric oxide synthase 2 Rattus norvegicus 61-65 7802762-6 1994 In the current study we extend observations on regulation of iNOS in RPASM by showing that de novo synthesis of tetrahydrobiopterin (BH4) is critical for LPS and cytokine-induced NO production. sapropterin 133-136 nitric oxide synthase 2 Rattus norvegicus 61-65 7504472-2 1993 This enzyme regulates the de novo synthesis pathway for tetrahydrobiopterin, an essential cofactor for the catalytic conversion of L-arginine to L-citrulline and NO by inducible NO synthase. sapropterin 56-75 nitric oxide synthase 2 Rattus norvegicus 168-189 27824007-12 2016 BH4 enhanced the production of NO in 2 Gy and 4 Gy radiated groups by upregulating eNOS protein expression and downregulating iNOS protein expression. sapropterin 0-3 nitric oxide synthase 2 Rattus norvegicus 126-130 27824007-13 2016 CONCLUSIONS: BH4 treatment can protect against X-ray-induced cardiomyocyte injury, possibly by recoupling eNOS rather than iNOS. sapropterin 13-16 nitric oxide synthase 2 Rattus norvegicus 123-127 33867911-6 2021 Furthermore, intrathecal injection of BH4 not only aggravated stress-induced hyperalgesia but also up-regulated the expression of spinal iNOS (iNOS mRNA: P = 0.015; iNOS protein: P < 0.001) and NO production (P < 0.001). sapropterin 38-41 nitric oxide synthase 2 Rattus norvegicus 143-147 33867911-6 2021 Furthermore, intrathecal injection of BH4 not only aggravated stress-induced hyperalgesia but also up-regulated the expression of spinal iNOS (iNOS mRNA: P = 0.015; iNOS protein: P < 0.001) and NO production (P < 0.001). sapropterin 38-41 nitric oxide synthase 2 Rattus norvegicus 143-147 16484312-1 2006 BACKGROUND: The deficiency of the inducible nitric oxide synthase (iNOS) substrate, L-arginine (L-Arg), the co-factor tetrahydrobiopterin (H4B) or molecular oxygen may lead to lower NO levels, which enhances the development of adhesion phenotype. sapropterin 118-137 nitric oxide synthase 2 Rattus norvegicus 34-65 23958248-2 2013 Optimal activity of iNOS is dependent on the intracellular availability of L-Arg and BH4 via prevention of NOS decoupling and subsequent ROS formation. sapropterin 85-88 nitric oxide synthase 2 Rattus norvegicus 20-24 23958248-9 2013 CONCLUSIONS: Fine-tuning of iNOS function by L-Arg and BH4 supplementation in the transduced vasculature augments the therapeutic potential of gene therapy with iNOS for the prevention of restenosis. sapropterin 55-58 nitric oxide synthase 2 Rattus norvegicus 28-32 23958248-9 2013 CONCLUSIONS: Fine-tuning of iNOS function by L-Arg and BH4 supplementation in the transduced vasculature augments the therapeutic potential of gene therapy with iNOS for the prevention of restenosis. sapropterin 55-58 nitric oxide synthase 2 Rattus norvegicus 161-165 18634867-2 2008 Tetrahydrobiopterin (BH(4)) is a key factor in the stabilization and NO production by iNOS homodimer. sapropterin 0-19 nitric oxide synthase 2 Rattus norvegicus 86-90 21182845-4 2011 The present study demonstrated that iNOS-derived superoxide generation was reduced, and that the NO bioavailability was increased, by treatment with the NOS-cofactor, tetrahydrobiopterin (BH4), before I/R in the hearts isolated from diabetic rats. sapropterin 188-191 nitric oxide synthase 2 Rattus norvegicus 36-40 21182845-6 2011 The cardioprotective effect of BH4 was abrogated by treatment with a thiol reducing agent dithiothreitol (DTT), but not a NO-sensitive guanylyl cyclase inhibitor ODQ, suggesting that iNOS-derived NO-mediated cardioprotection occurs through protein S-nitrosylation but not cGMP-dependent signaling in the diabetic heart. sapropterin 31-34 nitric oxide synthase 2 Rattus norvegicus 183-187 16488514-11 2006 However, manganese decreased iNOS enzymatic activity possibly through the depletion of cofactor since exogenous tetrahydrobiopterin reversed manganese"s action. sapropterin 112-131 nitric oxide synthase 2 Rattus norvegicus 29-33 16000090-2 2005 While NO production is determined by iNOS expression, BH4 (tetrahydrobiopterin), a cofactor of iNOS synthesized by GTP cyclohydrolase I, has been considered critical in sustaining NO production. sapropterin 54-57 nitric oxide synthase 2 Rattus norvegicus 95-99 16282548-4 2005 The present study tested the hypothesis that inhibition of endogenous BH4 rate-limiting enzyme GTP cyclohydrolase I (GTPCH I), and thus BH4 synthesis, reduces cerebral infarction via inhibiting iNOS and ONOO- in transient focal ischemia. sapropterin 70-73 nitric oxide synthase 2 Rattus norvegicus 194-198 16282548-4 2005 The present study tested the hypothesis that inhibition of endogenous BH4 rate-limiting enzyme GTP cyclohydrolase I (GTPCH I), and thus BH4 synthesis, reduces cerebral infarction via inhibiting iNOS and ONOO- in transient focal ischemia. sapropterin 136-139 nitric oxide synthase 2 Rattus norvegicus 194-198 16282548-12 2005 CONCLUSIONS: These results demonstrate that blockade of endogenous brain BH4 synthesis attenuates cerebral infarction via inhibiting iNOS and ONOO-, which may provide a mechanistic basis of novel therapeutic strategies for ischemic stroke. sapropterin 73-76 nitric oxide synthase 2 Rattus norvegicus 133-137 16000090-2 2005 While NO production is determined by iNOS expression, BH4 (tetrahydrobiopterin), a cofactor of iNOS synthesized by GTP cyclohydrolase I, has been considered critical in sustaining NO production. sapropterin 59-78 nitric oxide synthase 2 Rattus norvegicus 95-99 15808670-12 2005 Taken together, these observations suggest that NO derived from reactions driven by BH4-induced iNOS exerts a protective effect against reperfusion injury. sapropterin 84-87 nitric oxide synthase 2 Rattus norvegicus 96-100 15808670-11 2005 Western blotting showed a higher level of iNOS protein in the BH4 group than the saline group, 1400W suppressed this effect of BH4. sapropterin 62-65 nitric oxide synthase 2 Rattus norvegicus 42-46 15808670-11 2005 Western blotting showed a higher level of iNOS protein in the BH4 group than the saline group, 1400W suppressed this effect of BH4. sapropterin 127-130 nitric oxide synthase 2 Rattus norvegicus 42-46 15148691-1 2004 BACKGROUND: The synthesis of tetrahydrobiopterin (BH4), a necessary cofactor for inducible nitric oxide synthase (iNOS), has been reported to be controlled by guanosine triphosphate cyclohydrolase I (GTPCH). sapropterin 29-48 nitric oxide synthase 2 Rattus norvegicus 81-112 15148691-1 2004 BACKGROUND: The synthesis of tetrahydrobiopterin (BH4), a necessary cofactor for inducible nitric oxide synthase (iNOS), has been reported to be controlled by guanosine triphosphate cyclohydrolase I (GTPCH). sapropterin 29-48 nitric oxide synthase 2 Rattus norvegicus 114-118 15148691-1 2004 BACKGROUND: The synthesis of tetrahydrobiopterin (BH4), a necessary cofactor for inducible nitric oxide synthase (iNOS), has been reported to be controlled by guanosine triphosphate cyclohydrolase I (GTPCH). sapropterin 50-53 nitric oxide synthase 2 Rattus norvegicus 81-112 15148691-1 2004 BACKGROUND: The synthesis of tetrahydrobiopterin (BH4), a necessary cofactor for inducible nitric oxide synthase (iNOS), has been reported to be controlled by guanosine triphosphate cyclohydrolase I (GTPCH). sapropterin 50-53 nitric oxide synthase 2 Rattus norvegicus 114-118 12434606-3 2002 Guanosine triphosphate cyclohydrolase I (GTPCH) is the rate-limiting enzyme for the synthesis of tetrahydrobiopterin (BH4), a necessary co-factor for iNOS activity. sapropterin 97-116 nitric oxide synthase 2 Rattus norvegicus 150-154 12761298-8 2003 In addition, the IL-1beta-induced synthesis of tetrahydrobiopterin, a cofactor for iNOS, was also greatly stimulated by hypoxia in VSMC. sapropterin 47-66 nitric oxide synthase 2 Rattus norvegicus 83-87 12716655-3 2003 Glucocorticoids can inhibit iNOS activity in cultured cells by blocking arginine transport and inhibiting tetrahydrobiopterin biosynthesis. sapropterin 106-125 nitric oxide synthase 2 Rattus norvegicus 28-32 12434606-3 2002 Guanosine triphosphate cyclohydrolase I (GTPCH) is the rate-limiting enzyme for the synthesis of tetrahydrobiopterin (BH4), a necessary co-factor for iNOS activity. sapropterin 118-121 nitric oxide synthase 2 Rattus norvegicus 150-154 12039851-6 2002 Our findings support the hypothesis that BH4 can be used to modulate the function of the inflammatory iNOS isoform and suggest a potential therapeutic role for sepiapterin in early allograft rejection. sapropterin 41-44 nitric oxide synthase 2 Rattus norvegicus 102-106 10622266-12 1999 Thus, an excess amount of BH4 may be synthesized during NO production by iNOS in LPS-treated rat aorta. sapropterin 26-29 nitric oxide synthase 2 Rattus norvegicus 73-77 11711495-9 2001 The antihypertensive effect of H(4)B might be mediated through its direct antioxidant activity and/or decreasing oxygen free radical production from NO synthase, thereby reducing inducible NO synthase expression and peroxynitrite formation. sapropterin 31-36 nitric oxide synthase 2 Rattus norvegicus 179-200 10574472-3 1999 NO generation by inducible nitric oxide synthase (iNOS) is dependent on the presence of cofactors for NO generation, tetrathydrobiopterin (BH4) among them. sapropterin 139-142 nitric oxide synthase 2 Rattus norvegicus 17-48 10574472-3 1999 NO generation by inducible nitric oxide synthase (iNOS) is dependent on the presence of cofactors for NO generation, tetrathydrobiopterin (BH4) among them. sapropterin 139-142 nitric oxide synthase 2 Rattus norvegicus 50-54 10574472-5 1999 Therefore, the aim of our recent study was to investigate the influence of ox-LDL on the expression of iNOS and GTP cyclohydrolase I (GTP-CH I), the key enzyme involved in the BH4 synthesis as well as the ox-LDL effect on TGF-beta expression in rat macrophages stimulated with IFNgamma (250 U/ml) and LPS (500 ng/ml). sapropterin 176-179 nitric oxide synthase 2 Rattus norvegicus 103-107 10622266-1 1999 Tetrahydrobiopterin (BH4) is one of the cofactors of nitric oxide synthase (NOS), and the synthesis of BH4 is induced as well as inducible NOS (iNOS) by lipopolysaccharide (LPS) and/or cytokines. sapropterin 0-19 nitric oxide synthase 2 Rattus norvegicus 144-148 10622266-1 1999 Tetrahydrobiopterin (BH4) is one of the cofactors of nitric oxide synthase (NOS), and the synthesis of BH4 is induced as well as inducible NOS (iNOS) by lipopolysaccharide (LPS) and/or cytokines. sapropterin 21-24 nitric oxide synthase 2 Rattus norvegicus 144-148 10622266-7 1999 mRNAs of iNOS and GTP cyclohydrolase I (GTPCH), a rate-limiting enzyme of BH4 synthesis, were increased from 1.5 hr after addition of LPS. sapropterin 74-77 nitric oxide synthase 2 Rattus norvegicus 9-13 10622266-11 1999 These results suggest that although BH4 is essential for NO production from iNOS, the increase in BH4 content above the basal level is not needed for eliciting L-Arg-induced relaxation by the treatment with LPS. sapropterin 36-39 nitric oxide synthase 2 Rattus norvegicus 76-80 9572852-10 1998 On the contrary, the distal heme pocket of iNOS and nNOS seems to be closed after binding of l-Arg and BH4, particularly in the Fe(II) state. sapropterin 103-106 nitric oxide synthase 2 Rattus norvegicus 43-47 9473494-0 1998 Modulation of inducible nitric oxide synthase mRNA stability by tetrahydrobiopterin in vascular smooth muscle cells. sapropterin 64-83 nitric oxide synthase 2 Rattus norvegicus 14-45 9473494-1 1998 Tetrahydrobiopterin (BH4) regulates inducible nitric oxide synthase (iNOS) as cofactor and allosteric effector. sapropterin 0-19 nitric oxide synthase 2 Rattus norvegicus 36-67 9473494-1 1998 Tetrahydrobiopterin (BH4) regulates inducible nitric oxide synthase (iNOS) as cofactor and allosteric effector. sapropterin 0-19 nitric oxide synthase 2 Rattus norvegicus 69-73 9473494-1 1998 Tetrahydrobiopterin (BH4) regulates inducible nitric oxide synthase (iNOS) as cofactor and allosteric effector. sapropterin 21-24 nitric oxide synthase 2 Rattus norvegicus 36-67 9473494-1 1998 Tetrahydrobiopterin (BH4) regulates inducible nitric oxide synthase (iNOS) as cofactor and allosteric effector. sapropterin 21-24 nitric oxide synthase 2 Rattus norvegicus 69-73 9473494-9 1998 These data indicate that BH4 post-transcriptionally stabilizes iNOS mRNA in SMC. sapropterin 25-28 nitric oxide synthase 2 Rattus norvegicus 63-67 9473494-10 1998 By this way BH4 modulates iNOS expression in the vascular system. sapropterin 12-15 nitric oxide synthase 2 Rattus norvegicus 26-30