Rosiglitazone reduces angiotensin II and advanced glycation end product-dependent sustained nuclear factor-kappaB activation in cultured human proximal tubular epithelial cells.
Tubular damage is a major feature in the development of diabetic nephropathy. This study investigates the effects of the thiazolidindione rosiglitazone on angiotensin II and advanced glycation end product-induced tubular activation in human proximal tubular epithelial cells IN VITRO. Angiotensin II and advanced glycation end products, both induced a dose-dependent sustained activation of the redox-sensitive transcription factor, Nuclear Factor KAPPA B (NF-kappaB). Nuclear translocation of NF-kappaB was evident already after one hour and persistent for more than four days. Co-incubation of proximal tubular epithelial cells with rosiglitazone significantly reduced angiotensin II and advanced glycation end product-mediated generation of reactive oxygen species, angiotensin II-dependent advanced glycation end product formation, NF-kappaB activation, and NF-kappaB-dependent pro inflammatory gene expression. Most importantly, rosiglitazone effects on NFkappaB activation were maximal at later time points, indicating that rosiglitazone treatment confers long lasting renoprotective effects.
Morcos
M
M
Department of Internal Medicine 1 (Endocrinology, Metabolism and Clinical Chemistry), University of Heidelberg, Germany. michael_morcos@med.uni-heidelberg.de
Schlotterer
A
A
Sayed
A A R
AA
Kukudov
G
G
Oikomonou
D
D
Ibrahim
Y
Y
Pfisterer
F
F
Schneider
J
J
Bozorgmehr
F
F
Rudofsky
G
G
Schwenger
V
V
Kientsch-Engels
R
R
Hamann
A
A
Zeier
M
M
Dugi
K
K
Yard
B
B
Humpert
P M
PM
van der Woude
F
F
Nawroth
P P
PP
Bierhaus
A
A
D000804:Angiotensin II / Q000032:analysis* / Q000494:pharmacology / Q000502:physiology; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D003928:Diabetic Nephropathies / Q000517:prevention & control; D004847:Epithelial Cells / Q000737:chemistry / Q000378:metabolism; D015870:Gene Expression; D017127:Glycation End Products, Advanced / Q000494:pharmacology*; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007687:Kidney Tubules, Proximal / Q000737:chemistry / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D018384:Oxidative Stress; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000235:genetics; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology*; D014443:Tyrosine / Q000031:analogs & derivatives / Q000096:biosynthesis
D017127:Glycation End Products, Advanced; D007004:Hypoglycemic Agents; D016328:NF-kappa B; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D000804:Angiotensin II; C002744:3-nitrotyrosine; D014443:Tyrosine