MIB Seminar
Common Research Facilities
  • Laboratory of Embryonic and Genetic Engineering
  • Laboratory for Research Support
Contact

Medical Institute of Bioregulation Kyushu University
3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, JAPAN
TEL+81-92-642-6814
FAX+81-92-642-6246

The 779th MIB Seminar (Joint Usage/Research Center for the Multi-stratified Host Defense System)


[Seminar in English]

Title

The Role of OGG1 in doxorubicin-induced cardiotoxicity

Speaker

Dr. Chukwuemeka George Anene-Nzelu

Cardiovascular Research Institute,
Yong Loo Lin School of Medicine,
National University of Singapore

Date

Nov. 1 (Thu), 2018
15:00~16:30

Venue

Seminar Room, 1F, Main Building, Medical Institute of Bioregulation, Hospital Campus
No.31 on the following linked map.
(http://www.kyushu-u.ac.jp/f/33952/2018hospital_2-en.pdf)

Abstract

Doxorubicin is an anti-cancer drug widely used to treat a variety of malignancies. Its major adverse effect is a dose-dependent toxicity to the heart. The proposed mechanisms through which it produces cardiotoxicity includes oxidative stress, which leads to cardiac mitochondrial dysfunction, DNA damage and induction of apoptosis. 8-oxo-7,8-dihydroguanine (8-oxoG) is one of the most common DNA lesions induced by reactive oxygen species (ROS) and is considered an index of DNA damage. High levels of 8-oxoG have been correlated with increased mutation, loss of mitochondrial DNA, as well as apoptosis. 8-OxoG DNA glycosylase 1 encoded by OGG1 is the most important enzyme that recognizes and excises 8-oxoG and maintain low level of 8-oxoG in DNA thus preventing further cellular damage. We set out to study the effect of lack of OGG1 on cardiac functions following doxorubicin administration using Ogg1-knockout (KO) mice. Our results show that Ogg1-KO mice developed a more severe cardiac dilatation, greater reduction of ejection fraction and were more likely to die during the course of the treatment. RNA sequencing analysis showed upregulation of many genes involved in apoptosis in the Ogg1-KO hearts and this was confirmed in histological examination. These results thus demonstrate that OGG1 attenuates doxorubicin-induced cardiotoxicity by repairing 8-oxoG.

Speaker Introduction

Dr. Chukwuemeka George Anene-Nzelu is a Postdoctoral research fellow at the Cardiovascular Research Institute Singapore. He obtained his PhD in Tissue Engineering at the National University Singapore. He currently works on the role of DNA damage in heart failure as well as understanding 3D genome organization in the heart. This work was partly performed in the Cooperative Research Project Program of the Medical Institute of Bioregulation, Kyushu University.

Contact

Division of Neurofunctional Genomics, Department of Immunobiology and Neuroscience, Medical Institute of Bioregulation
Yusaku Nakabeppu
TEL: 092(642)6800

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