Characterization of GTP cyclohydrolase I gene expression in the human neuroblastoma SKN‐BE(2)M17: enhanced transcription in response to cAMP is conferred by the proximal promoter

Hirayama, Kei; Shimoji, Mika; Swick, Lance L.; Meyer, Amy; Kapatos, Gregory

doi:10.1046/j.0022-3042.2002.00773.x

Cited by 11 publications

(37 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…GTPCH1 activity is regulated by cAMP mediated pathway [26]. In the present study, Br-cAMP or Db-cAMP pretreatment to cells led to significant reversal of CRP-mediated inhibition of GTPCH1 activity (Fig 3c).…”

Section: Resultsmentioning

confidence: 67%

“…In this context, cell permeable analogue of cAMP, 8 Br-cAMP, which activates protein kinase A has been shown not only to result in restoration of GTPCH1 activity [26], but also attenuation of eNOS dysfunction [31,32]. Importantly, Hashimoto et al [43] reported the activation of eNOS by cilostazol via a cAMP/PKA and PI3K/Akt dependent mechanism.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, GTPCH1 enzyme has been reported to be regulated by cAMP-mediated pathway [26]. In this context, cell permeable analogue of cAMP, 8 Br-cAMP, which activates protein kinase A has been shown not only to result in restoration of GTPCH1 activity [26], but also attenuation of eNOS dysfunction [31,32].…”

Section: Discussionmentioning

confidence: 99%

“…Since GTPCH1 activity is known to be regulated by cAMP-mediated pathway [26], we first explored the involvement of this pathway in CRP-mediated GTPCH1 activity inhibition. The cells were treated with two different cAMP analogues (Calbiochem), Br-cAMP and db-cAMP (0.5 mM each separately) 1 hr prior to CRP treatment followed by the measurement of GTPCH1 activity.…”

Section: Crp and The Involvement Of Camp-mediated Pathway In Gtpch1 Amentioning

confidence: 99%

See 3 more Smart Citations

C-reactive protein decreases endothelial nitric oxide synthase activity via uncoupling

Singh

Devaraj

Vásquez‐Vivar

et al. 2007

Journal of Molecular and Cellular Cardiology

119

View full text Add to dashboard Cite

C-reactive protein (CRP), a cardiovascular risk marker, induces endothelial dysfunction. We have previously shown that CRP decreases endothelial nitric oxide synthase (eNOS) expression and bioactivity in human aortic endothelial cells (HAECs). In this study, we examined the mechanisms by which CRP decreases eNOS activity in HAECs. To this end, we explored different strategies such as availability of tetrahydrobiopterin (BH4) -a critical cofactor for eNOS, superoxide (O 2 -) production resulting in uncoupling of eNOS and phosphorylation/dephosphorylation of eNOS. CRP treatment significantly decreased levels of BH4 thereby promoting eNOS uncoupling. Pretreatment with sepiapterin, a BH4 precursor, prevented CRP-mediated effects on BH 4 levels, superoxide production as well as eNOS activity. The gene expression and enzymatic activity of GTPCH1, the first enzyme in the de novo biosynthesis of BH 4 , was significantly inhibited by CRP. Importantly, GTPCH1 is known to be regulated by cAMP mediated pathway. In the present study, CRP mediated inhibition of GTPCH1 activity was reversed by pretreatment with cAMP analogues. Furthermore, CRP-induced O 2 -production was reversed by pharmacologic inhibition and siRNAs to p47 phox and p22 phox. Additionally, CRP treatment significantly decreased the eNOS dimer:monomer ratio confirming CRP-mediated eNOS uncoupling. The pretreatment of cells with NO synthase inhibitor (N-nitro-L-arginine methyl ester [L-NAME]) also prevented CRP-mediated O 2 -production further strengthening CRP-mediated eNOS uncoupling. Additionally, CRP decreased eNOS phosphorylation at Ser1177 as well as increased phosphorylation at Thr495. CRP appears to mediate these effects through the Fcγ receptors, CD32 and CD64.To conclude, CRP uncouples eNOS resulting in increased superoxide production, decreased NO production, altered eNOS phosphorylation.

show abstract

Section: Resultsmentioning

confidence: 67%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Crp and The Involvement Of Camp-mediated Pathway In Gtpch1 Amentioning

confidence: 99%

See 2 more Smart Citations

C-reactive protein decreases endothelial nitric oxide synthase activity via uncoupling

Singh

Devaraj

Vásquez‐Vivar

et al. 2007

Journal of Molecular and Cellular Cardiology

119

View full text Add to dashboard Cite

show abstract

“…Western blots were performed with a rabbit anti-human antibody (1:5000 dilution), 19 and a goat anti-rabbit immunoglobulin G secondary antibody (1:10 000 dilution, Oncogene Research Products, San Diego, Calif) as previously described. 18 -20 …”

Section: Western Blot Analysis For Gtpch I Proteinmentioning

confidence: 99%

Gene Transfer of Human Guanosine 5′-Triphosphate Cyclohydrolase I Restores Vascular Tetrahydrobiopterin Level and Endothelial Function in Low Renin Hypertension

et al. 2003

Self Cite

View full text Add to dashboard Cite

Background-We recently reported that arterial superoxide (O 2Ϫ ) is augmented by increased endothelin-1 (ET-1) in deoxycorticosterone acetate (DOCA)-salt hypertension, a model of low renin hypertension. Tetrahydrobiopterin (BH 4 ), a potent reducing molecule with antioxidant properties and an essential cofactor for endothelial nitric oxide synthase, protects against O 2 Ϫ -induced vascular dysfunction. However, the interaction between O 2 Ϫ and BH 4 on endothelial function and the underlying mechanisms are unknown. Methods and Results-The present study tested the hypothesis that BH 4 deficiency due to ET-1-induced O 2 Ϫ leads to impaired endothelium-dependent relaxation and that gene transfer of human guanosine 5Ј-triphosphate (GTP) cyclohydrolase I (GTPCH I), the first and rate-limiting enzyme for BH 4 biosynthesis, reverses such deficiency and endothelial dysfunction in carotid arteries of DOCA-salt rats. There were significantly increased arterial O 2 Ϫ levels and decreased GTPCH I activity and BH 4 levels in DOCA-salt compared with sham rats. Treatment of arteries of DOCA-salt rats with the selective ET A receptor antagonist ABT-627, NADPH oxidase inhibitor apocynin, or superoxide dismutase (SOD) mimetic tempol abolished O 2 Ϫ and restored BH 4 levels. Basal arterial NO release and endothelium-dependent relaxations were impaired in DOCA-salt rats, conditions that were improved by apocynin or tempol treatment. Gene transfer of GTPCH I restored arterial GTPCH I activity and BH 4 levels, resulting in reduced O 2 Ϫ and improved endothelium-dependent relaxation and basal NO release in DOCA-salt rats. Conclusions-These

show abstract

Regulation of GTP cyclohydrolase I gene transcription by basic region leucine zipper transcription factors

Sarraj

Vinson

Han

et al. 2005

J of Cellular Biochemistry

View full text Add to dashboard Cite

Tetrahydrobiopterin is an essential cofactor for the phenylalanine, tyrosine and tryptophan hydroxylases, and the family of nitric oxide synthases. The initial and rate-limiting enzyme in the biosynthesis of tetrahydrobiopterin is GTP cyclohydrolase I. The proximal promoter of the human GTP cyclohydrolase I gene contains the sequence motif 5'-TGACGCGA-3', resembling a cAMP response element (CRE). The objective of this study was to analyze the regulation of GTP cyclohydrolase I gene transcription by basic region leucine zipper (bZIP) transcription factors. A constitutively active mutant of the cAMP response element binding (CREB) protein strongly stimulated GTP cyclohydrolase I promoter activity, indicating that the CRE in the context of the GTP cyclohydrolase I gene is functional. Likewise, GTP cyclohydrolase I promoter/luciferase gene transcription was stimulated following nuclear expression of the catalytic subunit of cAMP-dependent protein kinase. Constitutively active mutants of activating transcription factor 2 (ATF2) and c-Jun additionally stimulated GTP cyclohydrolase I promoter activity, but to a lesser extent than the constitutively active CREB mutant. The fact that stress-activated protein kinases target the GTP cyclohydrolase I gene was corroborated by expression experiments involving p38 and MEKK1 protein kinases. We conclude that signaling pathways involving either the cAMP-dependent protein kinase or stress-activated protein kinases converge to the GTP cyclohydrolase I gene. Hence, enzymatic reactions that require tetrahydrobiopterin as cofactor are therefore indirectly controlled by signaling cascades involving the signal-responsive transcription factors CREB, c-Jun, and ATF2.

show abstract

Characterization of GTP cyclohydrolase I gene expression in the human neuroblastoma SKN‐BE(2)M17: enhanced transcription in response to cAMP is conferred by the proximal promoter

Cited by 11 publications

References 16 publications

C-reactive protein decreases endothelial nitric oxide synthase activity via uncoupling

C-reactive protein decreases endothelial nitric oxide synthase activity via uncoupling

Gene Transfer of Human Guanosine 5′-Triphosphate Cyclohydrolase I Restores Vascular Tetrahydrobiopterin Level and Endothelial Function in Low Renin Hypertension

Regulation of GTP cyclohydrolase I gene transcription by basic region leucine zipper transcription factors

Contact Info

Product

Resources

About