Tadahisa Shono1,2, Nobuhiko Yokoyama3,2, Toshio Uesaka1, Junya Kuroda4,5, Ryu Takeya4, Tomoko Yamasaki4, Toshiyuki Amano1, Masahiro Mizoguchi1, Satoshi O. Suzuki6, Hiroaki Niiro7, Kyoko Miyamoto7, Koichi Akashi7, Toru Iwaki6, Hideki Sumimoto4, Tomio Sasaki1
1Department of Neurosurgery, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan
2T. Shono and N. Yokoyama contributed equally to this work.
3Department of Neurosurgery, Shinseikai Hospital, Kitakyushu, Japan
4Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan
5Medicine and Clinical Science, Kyushu University, Graduate School of Medical Sciences, Fukuoka, Japan
6Department of Neuropathology, Kyushu University, Graduate School of Medical Sciences, Fukuoka, Japan
7Center for Cellular and Molecular Medicine, Kyushu University Hospital, Fukuoka, Japan
Tóm tắt
AbstractReactive oxygen species (ROS) have been attracting attention as mediators of various cell‐signaling pathways. Nox‐family NADPH oxidases have proven to be a major source of ROS production in various cell types and have crucial roles in various physiological and pathological processes. In this study, we show that Nox4, a member of Nox family, is prominently expressed in various neuroepithelial tumors by reverse transcription‐polymerase chain reaction (RT‐PCR) and immunohistochemical studies. We quantified Nox4 mRNA expression by real‐time PCR in tumor specimens from 58 patients with astrocytomas and found that the expression levels of Nox4 mRNA in glioblastomas (WHO grade IV) were significantly higher than those in other astrocytomas (WHO grade II and III). In addition, we show that specific knockdown of Nox4 expression by RNA interference results in cell‐growth inhibition and enhances induction of apoptosis by chemotherapeutic agents, such as cisplatin, in cultured glioma cell lines. Based on these observations, enhanced expression of Nox4 appears to be involved in cell proliferation and survival in glioma cells. © 2008 Wiley‐Liss, Inc.
