1. Albumin overload induces adaptive responses in human proximal tubular cells through oxidative stress but not via angiotensin II type 1 receptor.
- Author
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Shalamanova L, McArdle F, Amara AB, Jackson MJ, and Rustom R
- Subjects
- Adaptation, Physiological drug effects, Angiotensin II pharmacology, Angiotensin II Type 1 Receptor Blockers pharmacology, Antioxidants metabolism, Benzimidazoles pharmacology, Biphenyl Compounds, Blotting, Western, Cell Line, Cell Nucleus drug effects, Cell Nucleus metabolism, Cell Shape, Cell Survival drug effects, DNA, Complementary biosynthesis, DNA, Complementary genetics, Endocytosis drug effects, Endocytosis physiology, Kidney Tubules, Proximal cytology, Lipid Metabolism drug effects, Lipid Peroxidation drug effects, Oxidative Stress genetics, RNA, Messenger biosynthesis, RNA, Messenger genetics, Receptor, Angiotensin, Type 1 drug effects, Reverse Transcriptase Polymerase Chain Reaction, Sulfhydryl Compounds metabolism, Tetrazoles pharmacology, Transcription Factors metabolism, Kidney Tubules, Proximal drug effects, Oxidative Stress physiology, Receptor, Angiotensin, Type 1 physiology, Serum Albumin pharmacology
- Abstract
Proteinuria is pathogenic to proximal tubular cells (PTC) and linked with progression to renal failure. The aim of this study was to determine the effects of human serum albumin (HSA) overload on the changes in gene and protein expression stimulated by oxidative stress in PTC and any interaction with ANG II that is pivotal in disease pathogenesis. Markers of oxidative stress, antioxidant defences, transcription factor activation, and the expression of stress-related genes were measured in human PTC (HK-2 cells) overloaded with either globulin-free fatty acid free (GF/FAF) HSA or globulin-free (GF) HSA. The effects of ANG II were also determined. HSA overload in HK-2 cells caused PTC hyperfunction, increased oxidative stress, and an upregulation of adaptive responses and stress-related genes. Some responses were common to both HSAs but others were unique to either HSA and unaffected by addition of ANG II or candesartan (a specific ANG II type 1 receptor blocker). ANG II also independently induced oxidative stress and upregulated other stress-related genes. HSA overload in HK-2 cells stimulated increased oxidative stress and upregulated changes in stress-related gene expression indicating new pathways of PTC injury that are not mediated via ANG II type 1 receptors.
- Published
- 2007
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