title: Extracellular signal-regulated kinase plays a proapoptotic role in podocytes after reactive oxygen species treatment and inhibition of integrin-extracellular matrix interaction.
abstract: The effect of reactive oxygen species (ROS) and blocking integrin-extracellular matrix (ECM) interaction on apoptosis in podocytes, and the related signal transduction pathways remain unclear. Primary cultured rat podocytes were exposed to ROS. Integrin-ECM interaction was inhibited with anti-β1-integrin monoclonal antibody (mAb) or RGDS (Arg-Gly-Asp-Ser). Extracellular signal-regulated kinase (ERK) activation was evaluated with Western blotting. U0126 was used to inhibit ERK activation. Terminal deoxynucleotidyl transferase-mediated dUTP-peroxidase nick end-labeling of DNA (TUNEL) was used to evaluate apoptosis. We found that ROS-treated podocytes exhibited increased apoptosis, and both anti-β1-integrin mAb and RGDS induce apoptosis. Addition of ROS to either anti-β1-integrin mAb or RGDS enhanced apoptosis in both conditions. ERK activation was increased by either ROS or blocking integrin-ECM interaction. Preincubation with U0126 decreased apoptosis induced by ROS, anti-β1-integrin mAb or RGDS, respectively. Our study demonstrated that ROS and blocking integrin-ECM interaction induce podocyte apoptosis, which is mediated by ERK activation.
authors: Division of Nephrology, Tainan Sinlau Hospital, Tainan 701, Taiwan.
authors: Chien-An
authors: CA
authors: Chen
authors: Tsang-Shan
authors: TS
authors: Chen
authors: Hung-Chun
authors: HC
authors: Chen
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D015153:Blotting, Western; D002070:Butadienes / Q000494:pharmacology; D004789:Enzyme Activation; D005109:Extracellular Matrix / Q000187:drug effects*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism / Q000502:physiology*; D020287:In Situ Nick-End Labeling; D019012:Integrin beta1 / Q000187:drug effects*; D009570:Nitriles / Q000494:pharmacology; D050199:Podocytes / Q000187:drug effects / Q000201:enzymology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000494:pharmacology*
chemical_list: D002070:Butadienes; D019012:Integrin beta1; D009570:Nitriles; D017382:Reactive Oxygen Species; C113580:U 0126; D048049:Extracellular Signal-Regulated MAP Kinases