F A C U L T Y P R O F I L E
FEINMARK, STEVEN J, PH.D.
Arachidonic acid metabolism in inflammatory cells and the nervous system; synthesis, biological and pharmacological activities of leuotrienes and PAF.
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Arachidonic acid metabolism in inflammatory cells and the nervous system; synthesis, biological and pharmacological activities of leuotrienes and PAF
Arachidonic acid is an essential fatty acid that is metabolized to diverse biologically active products. We study the lipoxygenase metabolites of arachidonate known as leukotrienes. The leukotrienes are important regulators of white blood cell function and therefore play a role in the inflammatory process. We previously demonstrated that leukotriene synthesis occurs through a cooperative interaction between white blood cells and the cells that line the inside of blood vessels, the endothelial cells. We have identified what appears to be a novel kinase that regulates one branch of this pathway. In proper balance, these interactions keep white blood cells from initiating an inflammatory reaction but after the appropriate biological signal, they may serve to amplify the response. We are using high-performance liquid chromatography, immunoassay and gas chromatography/mass spectrometry to measure the production of leukotrienes.
Our second area of interest relates to the role of lipids as signaling molecules in excitable cells. We have looked at the role of platelet-activating factor, a phospholipid made by white blood cells, as an initator of arrhythmias in isolated cardiac myocytes. A larger effort has focused on the synthesis and function of lipoxygenase products in the nervous system. As a model system, we are using the marine mollusk, Aplysia californica. Previously we identified 12-lipoxygenase products as second messengers in identified neurons. More recently, we have identified a new pathway initiated by the 8-lipoxygenase in this same tissue. This new pathway appears to be linked to an unusual, G-protein linked, nicotinic acetylcholine receptor. Continuing biochemical and parallel functional studies are in progress.
1. Plotnikov AN, Yu H, Geller JC, Gainullin RZ, Chandra P, Patberg KW, Friezema S, Danilo P Jr, Cohen IS, Feinmark SJ, Rosen MR. (2003) Role of L-type calcium channels in pacing-induced short-term and long-term cardiac memory in canine heart. Circulation 107:2844-9.
2. Barbuti A, Ishii S, Shimizu T, Robinson RB, Feinmark SJ. (2002) Block of the background K(+) channel TASK-1 contributes to arrhythmogenic effects of platelet-activating factor. Am J Physiol Heart Circ Physiol. 282:H2024-30.
3. Tieman TL, Steel DJ, Gor Y, Kehoe J, Schwartz JH, Feinmark SJ. (2001) A pertussis toxin-sensitive 8-lipoxygenase pathway is activated by a nicotinic acetylcholine receptor in aplysia neurons. J Neurophysiol. 85(5):2150-8.
4. Rybina IV, Feinmark SJ. (1999) Alteration of human leukotriene A4 hydrolase activity after site-directed mutagenesis: serine-415 is a regulatory residue. Biochim Biophys Acta. 1438(2):199-203.
5. Keramidas A. and Harrison N.L. (2010).
The activation mechanism of α1β2γ2 and α3β3γ2 GABAA receptors.
Journal of General Physiology, 135, 59-75.
6. Rybina IV, Liu H, Gor Y, Feinmark SJ. (1997) Regulation of leukotriene A4 hydrolase activity in endothelial cells by phosphorylation. J Biol Chem. 272(50):31865-71.
7. Anyukhovsky EP, Sosunov EA, Feinmark SJ, Rosen MR. (1997) Effects of quinidine on repolarization in canine epicardium, midmyocardium, and endocardium: II. In vivo study. Circulation 96(11):4019-26.