Stimulation of Tetrahydrobiopterin Synthesis by 17β-Estradiol in Brain Microvascular Endothelial Cells

Pteridines ◽  
2000 ◽  
Vol 11 (4) ◽  
pp. 129-132
Author(s):  
Kazuhiro Shiota ◽  
Masakazu Ishii ◽  
Toshinori Yamamoto ◽  
Shunichi Shimizu ◽  
Yuji Kiuchi
Keyword(s):  
Endothelial Cells ◽  
De Novo ◽  
Vascular Endothelial Cells ◽  
Mrna Level ◽  
Microvascular Endothelial Cells ◽  
No Production ◽  
Brain Microvascular Endothelial Cells ◽  
Protective Effects ◽  
17Β Estradiol ◽  
Microvascular Endothelial

Abstract The purpose of this study was to examine whether 17β-estradiol stimulates the synthesis of tetrahydrobiopterin : BH4), which is one of the cofactors of nitric oxide (NO) synthase, in mouse brain microvascular endothelial cells. Addition of 17()-estradiol to endothelial cells time- and concentration-dependently increased intracellular BH4 level. 17β-Estradiol also stimulated the mRNA level of GTP-cyclohydrolase I (GTPCH), which is a rate-limiting enzyme of the de novo BH4 synthetic pathway. In addition, the 17β-estradiol-induced expression of GTPCH mRNA was strongly attenuated by treatment with an inhibitor of 17β-estradiol receptor 4-hydroxy-tamoxlfen. These results suggest that 17β-estradiol stimulates BH4 synthesis through the induction of GTPCH by tamoxifensensitive receptor in vascular endothelial cells. The 17β-estradiol-induced increase in BH4 level might be implicated in not only NO production, but also protective effects of 17β-estradiol against ischemic brain damage and atherosclerosis, since BH4 is an intracellular antioxidant.

Stimulation of Tetrahydrobiopterin Synthesis by Cyclosporin A during Lipopolysaccharide Treatment in Vascular Endothelial Cells

Pteridines ◽  
2002 ◽  
Vol 13 (3) ◽  
pp. 89-93
Author(s):  
Masakazu Ishii ◽  
Shunichi Shimizu ◽  
Kazuhiro Shiota ◽  
Shinichiro Yamamoto ◽  
Yuji Kiuchi ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cyclosporin A ◽  
Vascular Endothelial Cells ◽  
Mrna Level ◽  
Microvascular Endothelial Cells ◽  
Inos Mrna ◽  
No Production ◽  
Brain Microvascular Endothelial Cells ◽  
Microvascular Endothelial ◽  
Lps Treatment

Abstract We examined the effect of immunosuppressant cyclosporin A (CsA) on the synthesis of tetrahydrobiopterin (BH4), which is a cofactor for nitric oxide synthase (NOS), during treatment with lipopolysaccharide (LPS) in mouse brain microvascular endothelial cells. Addition of LPS to the endothelial cells increased the BH4 content and the mRNA level of GTP-cyclohydrolase I (GTPCH), the rate-limiting enzyme of BH4 synthesis, and the LPSínduced increases in both the BH4 content and expression of GTPCH mRNA were further stimulated by the cotreatment with CsA. 2,4-Diamino-6-hydroxypyrimidine, an inhibitor of GTPCH, blocked the increase in BH4 content induced by CsA during the LPS treatment. Moreover. CsA stimulated the expression of inducible NOS (iNOS) mRNA during the LPS treatment. These findings suggest that CsA stimulates LPS-induced BH4 synthesis through the induction of GTPCH, and iNOS expression. CsA may increase NO production during LPS treatment in brain microvascular endothelial cells.

scholarly journals Human Induced Pluripotent Stem Cell-Derived Brain Endothelial Cells: Current Controversies

2021 ◽  
Vol 12 ◽  
Author(s):  
Tyler M. Lu ◽  
José Gabriel Barcia Durán ◽  
Sean Houghton ◽  
Shahin Rafii ◽  
David Redmond ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Stem Cell ◽  
Pluripotent Stem Cell ◽  
De Novo ◽  
Density Lipoprotein ◽  
Microvascular Endothelial Cells ◽  
Brain Microvascular Endothelial Cells ◽  
Brain Endothelial Cells ◽  
Microvascular Endothelial

Brain microvascular endothelial cells (BMECs) possess unique properties that are crucial for many functions of the blood-brain-barrier (BBB) including maintenance of brain homeostasis and regulation of interactions between the brain and immune system. The generation of a pure population of putative brain microvascular endothelial cells from human pluripotent stem cell sources (iBMECs) has been described to meet the need for reliable and reproducible brain endothelial cells in vitro. Human pluripotent stem cells (hPSCs), embryonic or induced, can be differentiated into large quantities of specialized cells in order to study development and model disease. These hPSC-derived iBMECs display endothelial-like properties, such as tube formation and low-density lipoprotein uptake, high transendothelial electrical resistance (TEER), and barrier-like efflux transporter activities. Over time, the de novo generation of an organotypic endothelial cell from hPSCs has aroused controversies. This perspective article highlights the developments made in the field of hPSC derived brain endothelial cells as well as where experimental data are lacking, and what concerns have emerged since their initial description.

scholarly journals Cronobacter sakazakii ATCC 29544 Translocated Human Brain Microvascular Endothelial Cells via Endocytosis, Apoptosis Induction, and Disruption of Tight Junction

2021 ◽  
Vol 12 ◽  
Author(s):  
Tong Jin ◽  
Ning Guan ◽  
Yuhang Du ◽  
Xinpeng Zhang ◽  
Jiahui Li ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Tight Junction ◽  
Human Brain ◽  
Microvascular Endothelial Cells ◽  
No Production ◽  
Mrna Levels ◽  
Brain Microvascular Endothelial Cells ◽  
Cronobacter Sakazakii ◽  
Microvascular Endothelial ◽  
Related Proteins

Cronobacter sakazakii (C. sakazakii) is an emerging opportunistic foodborne pathogen that can cause neonatal necrotizing enterocolitis, meningitis, sepsis in neonates and infants with a relatively high mortality rate. Bacterial transcytosis across the human brain microvascular endothelial cells (HBMEC) is vital for C. sakazakii to induce neonatal meningitis. However, few studies focus on the mechanisms by which C. sakazakii translocates HBMEC. In this study, the translocation processes of C. sakazakii on HBMEC were explored. C. sakazakii strains could effectively adhere to, invade and intracellularly survive in HBMEC. The strain ATCC 29544 exhibited the highest translocation efficiency across HBMEC monolayer among four tested strains. Bacteria-contained intracellular endosomes were detected in C. sakazakii-infected HBMEC by a transmission electron microscope. Endocytosis-related proteins CD44, Rab5, Rab7, and LAMP2 were increased after infection, while the level of Cathepsin L did not change. C. sakazakii induced TLR4/NF-κB inflammatory signal pathway activation in HBMEC, with increased NO production and elevated mRNA levels of IL-8, IL-6, TNF-α, IL-1β, iNOS, and COX-2. C. sakazakii infection also caused LDH release, caspase-3 activation, and HBMEC apoptosis. Meanwhile, increased Dextran-FITC permeability and decreased trans epithelial electric resistance indicated that C. sakazakii disrupted tight junction of HBMEC monolayers, which was confirmed by the decreased levels of tight junction-related proteins ZO-1 and Occludin. These findings suggest that C. sakazakii induced intracellular bacterial endocytosis, stimulated inflammation and apoptosis, disrupted monolayer tight junction in HBMEC, which all together contribute to bacterial translocation.

scholarly journals Insulin Stimulates Tetrahydrobiopterin Synthesis in Mouse Brain Microvascular Endothelial Cells

Pteridines ◽  
1999 ◽  
Vol 10 (4) ◽  
pp. 213-216
Author(s):  
Masakazu Ishi ◽  
Shunichi Shimizu ◽  
Tsutomu Nagai ◽  
Yuji Kiuchi ◽  
Toshinori Yamamoto
Keyword(s):  
Endothelial Cells ◽  
Mouse Brain ◽  
De Novo ◽  
Selective Inhibitor ◽  
Microvascular Endothelial Cells ◽  
Dependent Manner ◽  
Brain Microvascular Endothelial Cells ◽  
Gtp Cyclohydrolase I ◽  
Concentration Dependent Manner ◽  
Microvascular Endothelial

Summary We examined the effects of insulin on tetrahydrobiopterin (BH4) synthesis in mouse brain microvascular endothelial cells (MBMECs). Treatment of MBMECs with insulin increased the intracellular BH4 content in a time- and concentration-dependent manner. The insulin-induced increase in BH4 content was inhibited by treatment with 2,4-diamino-6-hydroxypyrimidine, a selective inhibitor of GTP cyclohydrolase I, and Nacetylserotonin, a selective inhibitor of sepiapterin reductase. These findings indicate that insulin stimulates BH4 synthesis in MBMECs through a de novo synthetic pathway of BH4.

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