Gene expression of 5-, 12-, and 15-lipoxygenases and leukotriene receptors along the rat nephron

American Journal of Physiology - Renal Physiology - Tập 290 Số 4 - Trang F864-F872 - 2006
Stephan W Reinhold1, Helga Vitzthum, Thomas Filbeck, Konrad Wolf, Christos Lattas, Günter A.J. Riegger, Armin Kurtz, Bernhard K. Krämer
1Klinik und Poliklinik für Innere Medizin II, University of Regensburg, Regensburg, Germany. [email protected]

Tóm tắt

The arachidonate signaling pathways comprise prostanoids formed by cyclooxygenases, EETs, and HETEs formed by cytochrome P-450 (CYP) enzymes and HETEs and leukotrienes generated by lipoxygenases. Whereas the intrarenal localization of cyclooxygenases and of some CYP enzymes along the nephron has already been determined, the localization of lipoxygenases and leukotriene-forming enzymes together with leukotriene receptors in the kidney is less clear. This study therefore aimed to determine the expression of 5-, 12-, and 15-lipoxygenases as well as the leukotriene receptors along the rat nephron. The kidneys were dissected into cortex and outer and inner medulla, and the microdissected nephron segments were collected after a collagenase digestion. mRNA abundance was determined by RT-PCR and real-time PCR. 15-LOX mRNA showed a characteristic expression pattern along the distal nephron. 12-LOX mRNA was only found in the glomerulus. Similarly, 5-LOX mRNAs together with 5-LOX-activating protein mRNAs were expressed in the glomerulus and also in the vasa recta. The leukotriene A4 hydrolase was found in all nephron segments, whereas leukotriene C4 synthase mRNA could not be found in any nephron segment. The leukotriene receptor B4 and the cysteinyl leukotriene receptor type 1 were selectively expressed in the glomerulus, whereas cysteinyl receptor type 2 was not found in any nephron segment. Our data suggest that the glomerulus is a major source and target for 5- and 12-HETE and for leukotrienes. The collecting duct system, on the other hand, appears to be a major source of 15-HETE.

Từ khóa


Tài liệu tham khảo

10.1161/01.HYP.10.1.61

10.1016/S0272-6386(12)80692-5

Badr KF.Five-lipoxygenase products in glomerular immune injury.J Am Soc Nephrol3: 907–915, 1992.

Chomczynski Pand Sacchi N.Single step method of RNA isolation by acid guadinium thiocyanate-phenol-chloroform extraction.Anal Biochem162: 156–159, 1987.

Claesson HE, Jakobsson PH, Steinhilber D, Odlander B, and Samuelsson B.Expression of 5-lipoxygenase and biosynthesis of leukotriene B4 in human monomorphonuclear leukocytes.J Lipid Mediat6: 15–22, 1993.

Evans JF.Cysteinyl leukotriene receptors.Prostaglandins Other Lipid Mediat68: 587–597, 2002.

10.1073/pnas.89.9.3962

Hedi Hand Norbert G.5-Lipoxygenase pathway, dendritic cells, and adaptive immunity.J Biomed Biotechnol2: 99–105, 2004.

10.1038/22572

10.1152/ajprenal.1998.274.2.F395

10.1073/pnas.89.8.3521

10.1006/pupt.1997.0075

10.1097/01.ASN.0000099702.16315.DE

10.1161/01.ATV.15.7.942

10.1046/j.1523-1755.2003.00286.x

10.1159/000075811

Labat C, Ortiz JL, Norel X, Gorenne I, Verley J, Abram TS, Cuthbert NJ, Tudhope SR, Norman P, Gardiner P and Brink C.A second cysteinyl receptor in human lung.J Pharmacol Exp Ther263: 800–805, 1992.

10.1016/S0006-291X(03)01456-6

10.1096/fj.02-0416fje

10.1046/j.1365-2249.1999.00858.x

10.1073/pnas.96.23.13375

10.1172/JCI115110

10.1046/j.1523-1755.1999.00257.x

Nie D, Tang K, Diglio C, and Honn KV.Eicosanoid regulation of angiogenesis: role of endothelial arachidonate 12-lipoxygenase.Blood95: 2304–2311, 2000.

10.1152/ajpregu.1997.273.1.R293

10.1152/ajprenal.00181.2002

10.1006/bbrc.2001.4865

10.1126/science.2820055

Sasaki M, Hori MT, Hino T, Golub MS, and Tuck ML.Elevated 12-lipoxygenase activity in the spontaneously hypertensive rat.Am J Hypertens10: 371–378, 1997.

10.1291/hypres.27.417

10.1152/ajprenal.1997.273.4.F650

Scoggan KA, Jakobsson PH, and Ford-Hutchinson AW.Production of leukotriene C4 in different human tissues is attributable to distinct membrane bound biosynthetic enzymes.J Biol Chem11: 10182–10187, 1997.

10.1006/bbrc.2000.3140

Valdivielso JM, Montero A, Badr KF, and Munger A.Inhibition of 5-lipoxygenase activating protein decreases proteinuria in diabetic rats.J Nephrol16: 85–94, 2003.

10.1046/j.1523-1755.2002.00615.x

10.1084/jem.178.6.1935

10.1038/ki.1993.180