tailieunhanh - Diazoxide attenuates ROS generation and exerts cytoprotection under conditions of ROS overproduction in rat uterus cells

Reactive oxygen species (ROS) overproduction may severely affect cell functions and even provoke cell death. Diazoxide, an opener of ATP-sensitive potassium channels, induces pharmacological preconditioning in different types of cells. | Turkish Journal of Biology Research Article Turk J Biol (2015) 39: 447-454 © TÜBİTAK doi: Diazoxide attenuates ROS generation and exerts cytoprotection under conditions of ROS overproduction in rat uterus cells Olga VADZYUK*, Sergiy KOSTERIN Palladin Institute of Biochemistry of the National Academy of Sciences of Ukraine, Kyiv, Ukraine Received: Accepted/Published Online: Printed: Abstract: Reactive oxygen species (ROS) overproduction may severely affect cell functions and even provoke cell death. Diazoxide, an opener of ATP-sensitive potassium channels, induces pharmacological preconditioning in different types of cells. However, the target of action of diazoxide is not clear enough because this substance can activate ATP-sensitive potassium channels localized in mitochondria (mitoKATP) as well as in plasma membranes (KATP channels). It has not yet been established if diazoxide activates mitoKATP in uterus cells. Our objective was to examine the influence of diazoxide on ROS production and on the viability of rat uterus cells under oxidative stress conditions. Using an ROS-sensitive fluorescent probe, we found that diazoxide enhances ROS production under normal conditions, but attenuates this process under conditions of ROS overproduction. Cells pretreated with diazoxide demonstrated lower levels of ROS production and of cell death under oxidative stress, in comparison with conditions where diazoxide was not present. The effects of diazoxide were eliminated by 5-hydroxydecanoate (5-HD), a blocker of mitoKATP. The principal conclusion of the present study is that decreased ROS production and increased cell survival in the presence of diazoxide under oxidative stress conditions are mediated by the activation of mitoKATP in rat uterus cells. Key words: Diazoxide, 5-hydroxydecanoate, mitoKATP, reactive oxygen species, uterus 1. Introduction Under normal physiological .