(5Z,11Z,15R)-15-Hydroxyeicosa-5,11-dien-13-ynoic acid: A stable isomer of 15(S)-HETE that retains key vasoconstrictive and antiproliferative activity. Prostaglandins Other Lipid Mediat 2016 Mar;123:33-9
Date
04/28/2016Pubmed ID
27117058Pubmed Central ID
PMC4893888DOI
10.1016/j.prostaglandins.2016.04.001Scopus ID
2-s2.0-84969584659 (requires institutional sign-in at Scopus site) 1 CitationAbstract
15(S)-Hydroxyeicosa-(5Z,8Z,11Z,13E)-tetraenoic acid (15(S)-HETE) is a metabolite of arachidonic acid that elicits a number of biological effects including vasoconstriction and angiogenesis. (5Z,11Z,15R)-15-Hydroxyeicosa-5,11-dien-13-ynoic acid (HETE analog 1) is a synthetic isomer of 15(S)-HETE that is much more stable to autoxidation. Using isometric recording of isolated pulmonary arteries from male and female rabbits, HETE analog 1 and 15(S)-HETE were found to elicit concentration-dependent contractions that were slightly greater in females compared to males. The maximal response in females was greater with 15(S)-HETE. HETE analog 1 and 15(S)-HETE increased [(3)H]-thymidine incorporation in vascular smooth muscle cells cultured from male rabbit pulmonary arteries; both the maximal response and potency were greater with 15(S)-HETE. In contrast, HETE analog 1 produced a concentration-dependent inhibition in proliferation and migration of human hormone-independent prostate carcinoma PC-3 cells. The protocol for synthesis of HETE analog 1 is reported. The stability of this substance and its similar biological profile to 15(S)-HETE support future studies in eicosanoid research.
Author List
Pfister SL, Klimko PG, Conrow REAuthor
Sandra L. Pfister PhD Professor in the Pharmacology and Toxicology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsArachidonate 15-Lipoxygenase
Biological Transport
Cell Line, Tumor
Cell Movement
Cell Proliferation
Dose-Response Relationship, Drug
Endothelial Cells
Female
Gene Expression
Humans
Hydroxyeicosatetraenoic Acids
Isomerism
Kinetics
Male
Primary Cell Culture
Pulmonary Artery
Rabbits
Sex Factors
Thymidine
Tissue Culture Techniques
Vasoconstriction
