1995 Fiscal Year Final Research Report Summary
Molecular mechanism and nutritional regulation of HIV-1-LTR transactivation by redox.
| Project/Area Number |
06806017
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
食品科学・栄養科学
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| Research Institution | Nagoya University |
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Principal Investigator |
ODA Hiroaki Nagoya University, Department of Applied Biological Sciences Assistant Professor, 農学部, 助手 (20204208)
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| Co-Investigator(Kenkyū-buntansha) |
KAKINUMA Atsushi Nagoya University, Department of Applied Biological Sciences Professor, 農学部, 教授 (50252276)
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| Project Period (FY) |
1994 – 1995
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| Keywords | intracellular redox / NF-kappaB / signal transduction / AIDS / molecular biology / untrition |
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| Research Abstract |
Transcriptional activation of HIV-1-LTR-CAT,which contains the transcription-regulatory region, by PMA (phorbol 12-mirystate 13-acetate), UVC (ultraviolet C ; 254nm) and TNFalpha (tumor necrosis factor alpha) was suppressed by the treatment of an antioxidant, PDTC (pyrrolidine dithiocarbamate). This results lead us to speculate that intracellular redox status serves as messengers mediating the activation of NF-kappaB.It has been demonstrated that the activation of NF-kappaB is suppressed by several antioxidants, such as NAC (N-acetyl L-cysteine), glutathione, vitamin E and lipoic acid. However, it is stil unknown which kind of ROI (reactive oxygen intermediates) is implicated in the activation of NF-kappaB.
To identify the ROI,we tested the effect of hydroxy radical scavengers (thiourea, ethanol, mannitol, DMSO (dimethyl sulfoxide), DMTU (dimethyl thiourea)), a singlet oxygen quencher (histidine), and an antioxidant (ascorbic acid) on the NF-kappaB activation. These scavengers and antioxidants did not reduce the activation of NF-kappaB by PMA,UVC and TNFalpha. Therefore, these data suggest that several kinds of ROI are not involved in the NF-kappaB activation, but redox status, such as a conversion between SH group and disulfide bond, is directly involved.
Moreover, we have found that DMSO enhances the activation of NF-kappaB by TNFalpha and PMA.DMSO alone does not activate NF-kappaB,and does not enhance the activation of NF-kappaB by UVC.DMSO accelerated the binding of NF-kappaB to kappaB oligonucleotide. The acceleration of NF-kappaB-DNA binding partly explains the enhancement of NF-kappaB activation by DMSO.
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