Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Experiment Videos

Acceleration of oxidative stress-induced endothelial cell death by nitric oxide synthase dysfunction accompanied with

M Ishii1, S Shimizu, T Yamamoto

  • 1Department of Clinical Pharmacy and Pharmacology, School of Pharmaceutical Sciences, Showa University, Shinagawa-ku, Tokyo, Japan.

Life Sciences
|January 1, 1997
PubMed
Summary
This summary is machine-generated.

Related Concept Videos

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Letter: liver dysfunction and survival in hepatocellular carcinoma treated by transarterial chemoembolisation.

Alimentary pharmacology & therapeutics·2012
Same author

Pollination biology in a lowland dipterocarp forest inSarawak, Malaysia. I. Characteristics of the plant-pollinator communityin a lowland dipterocarp forest.

American journal of botany·2011
Same author

Beetle pollination of Shorea parvifolia (section Mutica, Dipterocarpaceae) in a general flowering period in Sarawak, Malaysia.

American journal of botany·2011
Same author

Population fluctuations of light-attracted chrysomelid beetles in relation to supra-annual environmental changes in a Bornean rainforest.

Bulletin of entomological research·2008
Same author

Evaluation of an eye gaze point detection method using VEP elicited by multi-pseudorandom stimulation for brain computer interface.

Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference·2007
Same author

relationship between the binary kernels of visually evoked potentials and the visual responses on the magnocellular and parvocellular pathways.

Methods of information in medicine·2007

Nitric oxide synthase dysfunction and reduced tetrahydrobiopterin (BH4) increase H2O2-induced endothelial cell death by producing superoxide. Restoring BH4 or inhibiting nitric oxide synthase mitigates this oxidative stress and cell death.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Oxidative Stress Research

Background:

  • Nitric oxide (NO) plays a crucial role in endothelial function.
  • Dysfunction of NO synthase and altered tetrahydrobiopterin (BH4) levels are implicated in various pathologies.
  • Hydrogen peroxide (H2O2) is a key mediator of oxidative stress in endothelial cells.

Purpose of the Study:

  • To investigate if nitric oxide (NO) synthase dysfunction, coupled with decreased tetrahydrobiopterin (BH4) content, exacerbates H2O2-induced endothelial cell death.
  • To elucidate the role of BH4 and NO synthase activity in regulating superoxide production and oxidative stress in endothelial cells.

Main Methods:

  • Endothelial cell death was quantified by lactate dehydrogenase (LDH) release.
  • Intracellular BH4 levels were modulated using GTP cyclohydrolase I inhibitor (DAHP) or sepiapterin and measured via HPLC.

Related Experiment Videos

  • Superoxide production was detected using MCLA chemiluminescence.
  • NO synthase inhibition was achieved using L-NAME and L-NMA.

    • Main Results:

    • Pretreatment with DAHP significantly decreased intracellular BH4 levels and increased H2O2-induced endothelial cell death.
    • Sepiapterin or L-NAME treatment attenuated the toxic effects of DAHP and reduced superoxide production.
    • DAHP pretreatment enhanced ionomycin-induced superoxide production, an effect blocked by L-NAME but not L-NMA.
    • Sepiapterin co-pretreatment also decreased superoxide production.

    Conclusions:

    • Endothelial cell dysfunction of NO synthase, associated with reduced BH4, leads to superoxide generation instead of NO.
    • This shift towards superoxide production amplifies oxidative stress and contributes to endothelial cell death.
    • BH4 replenishment and appropriate NO synthase inhibition can mitigate oxidative stress and protect endothelial cells.