Kazushi Okada, PhD

Postdoctoral Fellow
Ph.D., Osaka City University Medical School, 2005


During my Ph.D. study at Osaka City University, I identified that the protein disulfide isomerase (PDI) is an important target protein for bisphenol A, a well-known endocrine disruptor. Furthermore, I found that several other phenolic compounds (xenoestrogens) can function like bisphenol A to inhibit the isomerase activity of PDI. These findings may shed light on the mechanism of the adverse effects of some phenolic environmental chemicals on the central nervous system. In addition, I found that PDI contributes to the thyroid hormone-induced production of growth hormone in GH3 cells. Together, my studies suggest that PDI may play a significant role in the central nervous system.

Research Interests

Many studies in the past decade have shown that oxidative stress is one of the important mechanisms of neuronal cell death during the development of neurodegenerative diseases. Generation of excess nitric oxide (NO) and other reactive oxygen species (ROS) can mediate protein misfolding. S-Nitrosylation, i.e., the covalent attachment of a NO group to the thiol side chain of cysteine, has emerged as an important mechanism for dynamic, posttranslational regulation of protein functions. S-Nitrosylation may convey a large part of the ubiquitous influence of NO on cellular signal transduction, by serving as a prototypic example of redox-based physiological regulation. Recent study suggests that alterations in S-nitrosylation-regulated signaling contribute to human diseases. It has been shown that S-nitrosylation of disulfide bond-containing proteins including PDI is one of the key events for neurodegenerative diseases. S-Nitrosylation of PDI triggers its dysfunction, allows the accumulation of polyubiquitinated proteins, and subsequently contributes to cell death. Importantly, PDI is S-nitrosylated in the brains of sporadic Alzheimer's and Parkinson's diseases which are characterized by abnormal protein accumulation. Therefore, S-nitrosylation likely represents one of the mechanisms contributing to NO-induced protein misfolding and neurotoxicity. My research interest centers around the better understanding of the pathogenic mechanism of neurodegenerative disorders and the identification of therapeutic approaches. Using HT22 mouse hippocampal neuronal cells as an in vitro model, I am currently studying the physiological and pathogenic functions of PDI and its related proteins in oxidative stress in the brain. Because recent studies have reported that mental conditions ranging from cognitive impairment to autism are linked to the exposure to certain environmental pollutants, I am also interested in studying the adverse effects of environmental chemicals on oxidative neurodegeneration, as well as the protective effect of estrogens against oxidative neuronal death.

Last modified: Dec 04, 2012

kokada

Contact

Kazushi Okada, PhD
Postdoctoral Fellow

4038A HLSIC; MS 1018
3901 Rainbow Blvd.
Kansas City, Kansas 66160

P: (913) 588-9180
F: (913) 588-7501
kokada@kumc.edu

Curriculum Vitae

ID=x9939