Aya Obara

Publications of Aya Obara

• ER stress inducer, thapsigargin, decreases extracellular-superoxide dismutase through MEK/ERK signalling cascades in COS7 cells.

  Authors: Tetsuro Kamiya, Aya Obara, Hirokazu Hara, Naoki Inagaki, Tetsuo Adachi

  Free radical research. 03/2011; 45(6):692-8.

  It has been reported that tubular cells suffer an endoplasmic reticulum (ER) stress during the development of chronic kidney disease, which is a potent risk factor of cardiovascular disease.It has been reported that tubular cells suffer an endoplasmic reticulum (ER) stress during the development of chronic kidney disease, which is a potent risk factor of cardiovascular disease. Moreover, under these conditions, reactive oxygen species are generated and induce cell injury. Extracellular-superoxide dismutase (EC-SOD) is a member of SODs and protects the cells from oxidative stress. Here, it is demonstrated that thapsigargin, an ER stress inducer, decreased EC-SOD expression, whereas the expression of Cu,Zn-SOD and Mn-SOD was not changed. On the other hand, another ER stress inducer, tunicamycin, did not affect the expression of EC-SOD. Further, it was shown that thapsigargin has the ability to activate extracellular-signal regulated kinase (ERK), but tunicamycin does not. Moreover, pre-treatment with U0126, an inhibitor of mitogen-activated protein kinase kinase (MEK)/ERK, suppressed thapsigargin-triggered EC-SOD reduction, suggesting that MEK/ERK signalling should play an important role in the regulation of EC-SOD in COS7 cells under ER stress conditions.

• Extracellular-superoxide dismutase expression in COS7 cells exposed to cadmium chloride.

  Authors: Aya Obara, Tetsuro Kamiya, Misato Izumi, Hirokazu Hara, Harutaka Yamada, Tetsuo Adachi

  Biological & pharmaceutical bulletin. 01/2011; 34(9):1443-7.

  Cadmium (Cd), an industrial and environmental pollutant, preferentially accumulates in the kidney, a major target for Cd-related toxicity. It has been reported that Cd exposure produces reactiveCadmium (Cd), an industrial and environmental pollutant, preferentially accumulates in the kidney, a major target for Cd-related toxicity. It has been reported that Cd exposure produces reactive oxygen species (ROS) and induces cytotoxicity. Extracellular-superoxide dismutase (EC-SOD) is an antioxidant enzyme that protects the cells from damaging effects of ROS; however, the effect of Cd on the expression of EC-SOD in COS7 cells remains unclear. In this study, exposure to cadmium chloride (CdCl₂) enhanced intracellular ROS generation and induced COS7 cell death. Moreover, exposure to Cd decreased the expression of EC-SOD at mRNA and protein levels, but not of other SOD isozymes, copper-and zinc-containing SOD and manganese-containing SOD. The reduction of EC-SOD and cell viability was partially attenuated by pretreatment with an antioxidant, N-acetylcysteine. Further, we determined the involvement of p38-mitogen-activated protein kinase (p38-MAPK) in the reduction of EC-SOD. From these observations, p38-MAPK signaling cascades activated by ROS play a pivotal role in the reduction of EC-SOD, and it is concluded that the reduction of EC-SOD leads to a decrease in the resistance to oxidative stress of Cd-exposed COS7 cells.