of the Max - MDC
of the Max - MDC
of the Max - MDC
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Structure <strong>of</strong> <strong>the</strong> Group<br />
Group Leader<br />
Dr. Wolf-Hagen Schunck<br />
Graduate Students<br />
Marija Markovic<br />
Cosima Schmidt<br />
Michael Oechsner<br />
Technical Assistants<br />
Christel Andree<br />
Ramona Zummach<br />
Kisselev, P, Schunck, WH, Roots, I, Schwarz, D. (2005).<br />
Association <strong>of</strong> CYP1A1 polymorphisms with differential metabolic<br />
activation <strong>of</strong> 17 beta-estradiol and estrone. Cancer Res 65,<br />
2972-8.<br />
Barbosa-Sicard, E, Markovic, M, Honeck, H, Christ, B, Muller, DN,<br />
Schunck, WH. (2005). Eicosapentaenoic acid metabolism by<br />
cytochrome P450 enzymes <strong>of</strong> <strong>the</strong> CYP2C subfamily. Biochem<br />
Biophys Res Commun. 329, 1275-81.<br />
Theuer, J, Shagdarsuen, E, Muller, DN, Kaergel, E, Honeck, H,<br />
Park, JK, Fiebeler, A, Dechend, R, Haller, H, Luft, FC, Schunck,<br />
WH. (2005). Inducible NOS inhibition, eicosapentaenoic acid<br />
supplementation, and angiotensin II-induced renal damage.<br />
Kidney Int. 67, 248-58.<br />
Generation and function <strong>of</strong> cytochrome P450 (CYP)-dependent eicosanoids in <strong>the</strong> cardiovascular system.<br />
1. Nutritional uptake <strong>of</strong> essential fatty acids (FA) and <strong>the</strong>ir celltype<br />
specific incorporation determines <strong>the</strong> acyl-chain composition<br />
<strong>of</strong> membrane phospholipids.<br />
2. Arachidonic acid (AA) and after appropriate nutrition also<br />
omega-3 FA such as eicosapentaenoic acid (EPA) are released by<br />
phospholipase A2 (PLA2) which is activated by various hormones<br />
and growth factors via <strong>the</strong>ir G-protein coupled receptors<br />
(GPCR).<br />
3. Free AA and EPA are now accessible and compete for conversion<br />
by CYP enzymes. Specificity <strong>of</strong> metabolite production is provided<br />
by cell-type specific expression <strong>of</strong> individual CYP4A/4F- and<br />
CYP2C/2J-family members which are distinguished by unique<br />
regio- and stereoselectivities. CYP enzymes are inhibited by nitric<br />
oxide (NO), carbon monoxide (CO) and reactive oxygen species<br />
(ROS) which are produced in variable amounts depending on<br />
inflammation and o<strong>the</strong>r disease states.<br />
4. CYP-dependent eicosanoids serve as second messengers in pathways<br />
regulating vascular, renal and cardiac function. Individual<br />
eicosanoids modulate (i) <strong>the</strong> activity <strong>of</strong> ion channels adjusting<br />
cell membrane potential or mediating salt reabsorption and (ii)<br />
<strong>the</strong> activation <strong>of</strong> pro-inflammatory transcription factors and<br />
mitogen-activated protein kinases.<br />
Cardiovascular and Metabolic Disease Research 19
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