Protection against Oxidative Stress, Inflammation, and Apoptosis of High-Glucose-Exposed Proximal Tubular Epithelial Cells by Astaxanthin

2009 ◽  
Vol 57 (19) ◽  
pp. 8793-8797 ◽  
Author(s):  
You Jung Kim ◽  
Young Ae Kim ◽  
Takako Yokozawa
Keyword(s):  
Oxidative Stress ◽  
Epithelial Cells ◽  
High Glucose ◽  
Tubular Epithelial Cells ◽  
Proximal Tubular Epithelial Cells ◽  
Proximal Tubular

High glucose‐induced oxidative stress causes apoptosis in proximal tubular epithelial cells and is mediated by multiple caspases

2003 ◽  
Vol 17 (8) ◽  
pp. 1-21 ◽  
Author(s):  
David A. Allen ◽  
Steven M. Harwood ◽  
Mira Varagunam ◽  
Martin J. Raftery ◽  
Muhammad M. Yaqoob
Keyword(s):  
Oxidative Stress ◽  
Epithelial Cells ◽  
High Glucose ◽  
Tubular Epithelial Cells ◽  
Proximal Tubular Epithelial Cells ◽  
Proximal Tubular

scholarly journals High Glucose Increases Metallothionein Expression in Renal Proximal Tubular Epithelial Cells

2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Daisuke Ogawa ◽  
Masato Asanuma ◽  
Ikuko Miyazaki ◽  
Hiromi Tachibana ◽  
Jun Wada ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetic Nephropathy ◽  
Vitamin E ◽  
Epithelial Cells ◽  
High Glucose ◽  
Male Rats ◽  
Tubular Epithelial Cells ◽  
Proximal Tubular Epithelial Cells ◽  
Proximal Tubular ◽  
Renal Proximal Tubular

Metallothionein (MT) is an intracellular metal-binding, cysteine-rich protein, and is a potent antioxidant that protects cells and tissues from oxidative stress. Although the major isoforms MT-1 and -2 (MT-1/-2) are highly inducible in many tissues, the distribution and role of MT-1/-2 in diabetic nephropathy are poorly understood. In this study, diabetes was induced in adult male rats by streptozotocin, and renal tissues were stained with antibodies for MT-1/-2. MT-1/-2 expression was also evaluated in mProx24 cells, a mouse renal proximal tubular epithelial cell line, stimulated with high glucose medium and pretreated with the antioxidant vitamin E. MT-1/-2 expression was gradually and dramatically increased, mainly in the proximal tubular epithelial cells and to a lesser extent in the podocytes in diabetic rats, but was hardly observed in control rats. MT-1/-2 expression was also increased by high glucose stimulation in mProx24 cells. Because the induction of MT was suppressed by pretreatment with vitamin E, the expression of MT-1/-2 is induced, at least in part, by high glucose-induced oxidative stress. These observations suggest that MT-1/-2 is induced in renal proximal tubular epithelial cells as an antioxidant to protect the kidney from oxidative stress, and may offer a novel therapeutic target against diabetic nephropathy.

scholarly journals Metallothionein deficiency exacerbates diabetic nephropathy in streptozotocin-induced diabetic mice

2014 ◽  
Vol 306 (1) ◽  
pp. F105-F115 ◽  
Author(s):  
Hiromi Tachibana ◽  
Daisuke Ogawa ◽  
Norio Sogawa ◽  
Masato Asanuma ◽  
Ikuko Miyazaki ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetic Nephropathy ◽  
Epithelial Cells ◽  
High Glucose ◽  
Tubular Epithelial Cells ◽  
Diabetic Kidney ◽  
Proximal Tubular Epithelial Cells ◽  
Proximal Tubular ◽  
In The Diabetic Kidney

Oxidative stress and inflammation play important roles in diabetic complications, including diabetic nephropathy. Metallothionein (MT) is induced in proximal tubular epithelial cells as an antioxidant in the diabetic kidney; however, the role of MT in renal function remains unclear. We therefore investigated whether MT deficiency accelerates diabetic nephropathy through oxidative stress and inflammation. Diabetes was induced by streptozotocin injection in MT-deficient (MT−/−) and MT+/+ mice. Urinary albumin excretion, histological changes, markers for reactive oxygen species (ROS), and kidney inflammation were measured. Murine proximal tubular epithelial (mProx24) cells were used to further elucidate the role of MT under high-glucose conditions. Parameters of diabetic nephropathy and markers of ROS and inflammation were accelerated in diabetic MT−/− mice compared with diabetic MT+/+ mice, despite equivalent levels of hyperglycemia. MT deficiency accelerated interstitial fibrosis and macrophage infiltration into the interstitium in the diabetic kidney. Electron microscopy revealed abnormal mitochondrial morphology in proximal tubular epithelial cells in diabetic MT−/− mice. In vitro studies demonstrated that knockdown of MT by small interfering RNA enhanced mitochondrial ROS generation and inflammation-related gene expression in mProx24 cells cultured under high-glucose conditions. The results of this study suggest that MT may play a key role in protecting the kidney against high glucose-induced ROS and subsequent inflammation in diabetic nephropathy.

scholarly journals Toll-Like Receptor 4/Spleen Tyrosine Kinase Complex in High Glucose Signal Transduction of Proximal Tubular Epithelial Cells

2015 ◽  
Vol 35 (6) ◽  
pp. 2309-2319 ◽  
Author(s):  
Won Seok Yang ◽  
Joon-Seok Kim ◽  
Nam Jeong Han ◽  
Mee Jeong Lee ◽  
Su-Kil Park
Keyword(s):  
Signal Transduction ◽  
Epithelial Cells ◽  
Tyrosine Kinase ◽  
High Glucose ◽  
Toll Like Receptor ◽  
Tubular Epithelial Cells ◽  
Spleen Tyrosine Kinase ◽  
Toll Like Receptor 4 ◽  
Proximal Tubular Epithelial Cells ◽  
Proximal Tubular

Background/Aims: High glucose activates spleen tyrosine kinase (Syk) in human proximal tubular epithelial cells (HK-2 cells), which leads to NF-κB activation and transforming growth factor-ß1 (TGF-ß1) production. We explored the signal transduction pathway from high glucose to Syk activation. Methods: The pathway was evaluated by siRNA transfection, immunoprecipitation and Western blot. Results: High glucose stimulated Syk activation within 10 min. Depletion of toll-like receptor 4 (TLR4) attenuated high glucose-induced Syk activation, NF-κB p65 nuclear translocation, and TGF-ß1 production. In addition, TLR4 inhibitor (CLI-095), TLR4-neutralizing antibody, and depletion of myeloid differentiation factor 88 (MyD88) all attenuated high glucose-induced Syk activation. As an evidence of TLR4 activation, interleukin-1 receptor-associated kinase 1 was recruited to MyD88 and TLR4 upon exposure to high glucose. Syk was co-immunoprecipitated with TLR4, and Syk bound to TLR4 was activated by high glucose. High-mobility group box-1 (HMGB-1), an endogenous activator of TLR4, rapidly increased in TLR4 immunoprecipitates upon high glucose stimulation, and this association was reduced by N-acetylcysteine, an antioxidant. An HMGB-1 inhibitor glycyrrhizin suppressed high glucose-induced Syk activation. Conclusion: Syk is constitutively associated with TLR4. High glucose induces an immediate, reactive oxygen species-dependent, extracellular release of HMGB-1 which binds to TLR4 and activates it, leading to Syk activation.

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