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.

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 in mouse brain microvascular endothelial cells

2002 ◽  
Vol 34 (9) ◽  
pp. 1134-1141 ◽  
Author(s):  
Masakazu Ishii ◽  
Shunichi Shimizu ◽  
Kazuhiro Shiota ◽  
Shinichiro Yamamoto ◽  
Yuji Kiuchi ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cyclosporin A ◽  
Mouse Brain ◽  
Microvascular Endothelial Cells ◽  
Brain Microvascular Endothelial Cells ◽  
Microvascular Endothelial ◽  
Stimulation Of

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 Ubiquinone Metabolism and Transcription HIF-1 Targets Pathway Are Toxicity Signature Pathways Present in Extracellular Vesicles of Paraquat-Exposed Human Brain Microvascular Endothelial Cells

2021 ◽  
Vol 22 (10) ◽  
pp. 5065
Author(s):  
Tatjana Vujić ◽  
Domitille Schvartz ◽  
Anton Iliuk ◽  
Jean-Charles Sanchez
Keyword(s):  
Endothelial Cells ◽  
Human Brain ◽  
Extracellular Vesicles ◽  
Physiological State ◽  
Microvascular Endothelial Cells ◽  
Brain Microvascular Endothelial Cells ◽  
Cell Of Origin ◽  
Functional Changes ◽  
Data Independent Acquisition ◽  
Microvascular Endothelial

Over the last decade, the knowledge in extracellular vesicles (EVs) biogenesis and modulation has increasingly grown. As their content reflects the physiological state of their donor cells, these “intercellular messengers” progressively became a potential source of biomarker reflecting the host cell state. However, little is known about EVs released from the human brain microvascular endothelial cells (HBMECs). The current study aimed to isolate and characterize EVs from HBMECs and to analyze their EVs proteome modulation after paraquat (PQ) stimulation, a widely used herbicide known for its neurotoxic effect. Size distribution, concentration and presence of well-known EV markers were assessed. Identification and quantification of PQ-exposed EV proteins was conducted by data-independent acquisition mass spectrometry (DIA-MS). Signature pathways of PQ-treated EVs were analyzed by gene ontology terms and pathway enrichment. Results highlighted that EVs exposed to PQ have modulated pathways, namely the ubiquinone metabolism and the transcription HIF-1 targets. These pathways may be potential molecular signatures of the PQ-induced toxicity carried by EVs that are reflecting their cell of origin by transporting with them irreversible functional changes.

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