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

Functional characterization of cyclooxygenase-2 polymorphisms.

E Fritsche1, S J Baek, L M King

  • 1Laboratory of Computational Biology and Risk Analysis, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA.

The Journal of Pharmacology and Experimental Therapeutics
|October 17, 2001
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

Regulation of chemicals demands assessment of risks rather than identification of hazards only.

Archives of toxicology·2026
Same author

Magnetic Resonance Imaging-Negative Cerebral Amyloid Angiopathy: Cerebrospinal Fluid Amyloid-β42 over Amyloid Positron Emission Tomography.

The journal of prevention of Alzheimer's disease·2024
Same author

Longitudinal stability of molecular alterations and drug response profiles in tumor spheroid cell lines enables reproducible analyses.

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie·2021
Same author

Risk factors for local recurrence and long term survival after minimally invasive intersphincteric resection for very low rectal cancer: Multivariate analysis in 161 patients.

European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology·2021
Same author

Implementing simple algorithms to improve glucose and lipid management in people with diabetes and acute coronary syndrome.

Diabetic medicine : a journal of the British Diabetic Association·2019
Same author

Patients with type 1 diabetes in a tertiary setting do not attain recommended lipid targets.

Diabetes & metabolism·2019

Genetic variations in cyclooxygenase-2 (COX-2) were investigated for their impact on enzyme function and drug response. Rare COX-2 polymorphisms were found, but none altered enzyme activity or NSAID sensitivity, suggesting functional conservation.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Genetics

Background:

  • Cyclooxygenases (COX)-1 and -2 are key enzymes in prostaglandin synthesis.
  • COX-2 is implicated in inflammation and carcinogenesis.
  • Nonsteroidal anti-inflammatory drugs (NSAIDs) treat diseases and may reduce colorectal cancer risk.

Purpose of the Study:

  • To investigate the functional impact of cyclooxygenase-2 (COX-2) gene polymorphisms.
  • To determine if COX-2 variants affect enzyme activity, substrate metabolism, or response to NSAIDs.
  • To explore the implications of COX-2 polymorphisms on cancer risk and drug sensitivity.

Main Methods:

  • Sequencing of the COX-2 gene in 72 individuals to identify polymorphisms.
  • Utilizing a COX-2 molecular model to map coding region variants.

Related Experiment Videos

  • Expressing and evaluating the function of the COX-2 V511A variant protein.
  • Assessing substrate metabolism (arachidonic acid, linoleic acid, 2-arachidonyl glycerol) and enzyme kinetics (Km values).
  • Testing inhibition by selective and nonselective COX inhibitors.

    • Main Results:

    • Rare polymorphisms were identified in the COX-2 promoter and coding regions.
    • The COX-2 V511A polymorphism, located near the active site, showed no difference in substrate metabolism compared to wild-type.
    • Kinetic analysis revealed no significant differences in Km values for arachidonic acid.
    • Inhibition patterns with COX inhibitors were similar for both wild-type and V511A mutant enzymes.

    Conclusions:

    • The absence of functionally significant COX-2 polymorphisms suggests strong selective pressure against variants that could impair enzyme function.
    • These findings indicate that COX-2's critical role in maintaining homeostasis may limit the occurrence of functionally impactful genetic variations.
    • The identified rare polymorphisms likely do not significantly alter individual risks for cancer or responses to NSAIDs.