help button home button Am J Pathol Epitomics Buy 2 Antibodies Get 1 Free Special Offer
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Porubsky, S.
Right arrow Articles by Gröne, H.-J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Porubsky, S.
Right arrow Articles by Gröne, H.-J.
(American Journal of Pathology. 2004;164:2175-2187.)
© 2004 American Society for Investigative Pathology

Influence of Native and Hypochlorite-Modified Low-Density Lipoprotein on Gene Expression in Human Proximal Tubular Epithelium

Stefan Porubsky*, Holger Schmid{dagger}, Mahnaz Bonrouhi*, Matthias Kretzler{dagger}, Ernst Malle{ddagger}, Peter J. Nelson{dagger} and Hermann-Josef Gröne*

From the Department of Cellular and Molecular Pathology,* German Cancer Research Center, Heidelberg, Germany; the Medizinische Poliklinik,{dagger} Ludwig-Maximilians-University of Munich, Munich, Germany; and the Institute of Medical Biochemistry and Molecular Biology,{ddagger} Medical University, Graz, Austria

Inflammatory infiltrates can modify (lipo)proteins via hypochlorous acid/hypochlorite (HOCl/OCl–) an oxidant formed by the myeloperoxidase-H2O2-halide system. These oxidatively modified proteins emerge in tubuli in some proteinuric and interstitial diseases. Human proximal tubular cells (HK-2) were used to confirm the hypothesis of detrimental and differential impact of HOCl-modified low density lipoprotein (HOCl-LDL), an in vivo occurring lipoprotein modification exerting proatherogenic and proinflammatory capacity. HOCl-LDL showed dose-dependent antiproliferative effects in HK-2 cells. Small dedicated cDNA macroarrays were used to identify differentially regulated genes. A rapid increase in the expression of genes involved in reactive oxygen species metabolism and cell stress, eg, heme oxygenase-1, thioredoxin reductase, cytochrome b5 reductase, Gadd 153, amino acid transporter E16, and HSP70 was found after HOCl-LDL treatment of HK-2 cells. In parallel, genes involved in tissue remodeling and inflammation eg, CTGF, VCAM-1, IL-1ß, MMP7, and VEGF were up-regulated. Quantitative RT-PCR verified differential expression of a subset of these genes in microdissected tubulointerstitia from patients with acute tubular damage, progressive proteinuric renal disease, and membranous glomerulonephritis (with declining renal function), but not in stable patients with proteinuria caused by minimal change disease. The demonstration of selective up-regulation of a subgroup of genes if proteinuria is accompanied by the presence of HOCl-modified (lipo)proteins support the potential pathophysiological role of the myeloperoxidase-H2O2-halide system and HOCl-LDL in renal disease.




This article has been cited by other articles:


Home page
 EndocrinologyHome page
X. Y. Shi, F. F. Hou, H. X. Niu, G. B. Wang, D. Xie, Z. J. Guo, Z. M. Zhou, F. Yang, J. W. Tian, and X. Zhang
Advanced Oxidation Protein Products Promote Inflammation in Diabetic Kidney through Activation of Renal Nicotinamide Adenine Dinucleotide Phosphate Oxidase
Endocrinology, April 1, 2008; 149(4): 1829 - 1839.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
Z. V. Popovic, R. Sandhoff, T. P. Sijmonsma, S. Kaden, R. Jennemann, E. Kiss, E. Tone, F. Autschbach, N. Platt, E. Malle, et al.
Sulfated Glycosphingolipid as Mediator of Phagocytosis: SM4s Enhances Apoptotic Cell Clearance and Modulates Macrophage Activity
J. Immunol., November 15, 2007; 179(10): 6770 - 6782.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
H. Y. Li, F. F. Hou, X. Zhang, P. Y. Chen, S. X. Liu, J. X. Feng, Z. Q. Liu, Y. X. Shan, G. B. Wang, Z. M. Zhou, et al.
Advanced Oxidation Protein Products Accelerate Renal Fibrosis in a Remnant Kidney Model
J. Am. Soc. Nephrol., February 1, 2007; 18(2): 528 - 538.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
M. Wornle, H. Schmid, B. Banas, M. Merkle, A. Henger, M. Roeder, S. Blattner, E. Bock, M. Kretzler, H.-J. Grone, et al.
Novel Role of Toll-Like Receptor 3 in Hepatitis C-Associated Glomerulonephritis
Am. J. Pathol., February 1, 2006; 168(2): 370 - 385.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
R. Sandhoff, R. Geyer, R. Jennemann, C. Paret, E. Kiss, T. Yamashita, K. Gorgas, T. P. Sijmonsma, M. Iwamori, C. Finaz, et al.
Novel Class of Glycosphingolipids Involved in Male Fertility
J. Biol. Chem., July 22, 2005; 280(29): 27310 - 27318.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
J. Adams, E. Kiss, A. B.V. Arroyo, M. Bonrouhi, Q. Sun, Z. Li, N. Gretz, A. Schnitger, C. C. Zouboulis, M. Wiesel, et al.
13-cis Retinoic Acid Inhibits Development and Progression of Chronic Allograft Nephropathy
Am. J. Pathol., July 1, 2005; 167(1): 285 - 298.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2004 by the American Society for Investigative Pathology.