1999 Fiscal Year Final Research Report Summary
ANALYSIS OF OXIDATIVE STRESS INDUCED APOPTOSIS MECHANISM AND THE BINDING PROTEINS TO THE OXIDATIVE RESPONSIVE ELEMENT
| Project/Area Number |
10670139
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Pathological medical chemistry
|
|---|
| Research Institution | KYOTO UNIVERSITY |
|---|
Principal Investigator |
MASUTANI Hiroshi Institute for Virus Research, Kyoto University Assistant Professor, ウイルス研究所, 助手 (50252523)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
YODOI Junji Institute for Virus Research, Kyoto University Professor, ウイルス研究所, 教授 (80108993)
|
|---|
| Project Period (FY) |
1998 – 1999
|
| Keywords | OXIDATIVE STRESS / THIOREDOXIN / APOPTOSIS / DIOXIN / PROMOTER / Nrf2 / p53 / CANCER |
|---|
| Research Abstract |
To investigate the molecular mechanism of oxidative stress related pathological conditions such as inflammation, reperfusion injury, carcinogenesis, and allergy, we have studied the mechanism of oxidative stress signaling and response.
We have obtained the following results.
1. We revealed that cytochrome c release and redox control is important for the induction of apoptosis by a flavonoid compound. We showed that 3-methylcholanthrene (MC), apolycyclic aromatic hydrocarbon and a carcinogen, caused p53 activation, resulting in apoptosis and cell cycle arrest. We also demonstrated that thioredoxin (TRX) and Redox factor 1 (Ref-1) is involved in the p53-dependent activation of p21 (Ueno et al.). We also reported that the regulation of Bcl-2 and TRX expression is important for the establishment of persistent infection of HIV and that the expression is actually associated with viral load (Elbim et al., in collaboration with Dr. N. Israel).
2. TRX is an important redox regulator and has cytoprotective activities against oxidative stress. TRX is induced by a wide variety of oxidative stresses. We have identified the hemin responsive element in the TRX promoter. The element contains the antioxidant responsive element (ARE). We revealed that NF-E2p45 and Nrf2 bind to the element and activate the TRX gene (manuscript in preparation). We also showed that a region in the TRX promoter, containing the xenobiotic responsive element (XRE) and SP-1 site is important for the response to polycyclic aromatic hydrocarbons such as MC. We are also screening the binding proteins to the oxidative responsive element of the TRX promoter using yeast one hybrid assay. In addition, we identified TRX binding proteins (Nishiyama et al.).
|
