EFFECTS OF SHORT-AND LONG-TERM FLEX-HET THERAPY ON MITOCHONDRIAL ELECTRON
EFFECTS OF SHORT-AND LONG-TERM FLEX-HET THERAPY ON MITOCHONDRIAL ELECTRON
批准号:
8167537
负责人:
KELLY J WILLIAM
金额:
$6.6万
依托单位国家:
美国
项目类别:
财政年份:
2010
资助国家:
美国
项目状态:
已结题
起止时间:
2010-04-01 至 2011-03-31
关键词:
AnimalsApoptosisAutopsyCell DeathCellsColon CarcinomaComplexComputer Retrieval of Information on Scientific Projects DatabaseCytochromesDrug Delivery SystemsElectron TransportElectronsFreezingFundingGenerationsGlutathioneGrantHeartHepatocyteInjuryInstitutionLeadLiverMeasuresMembraneMitochondriaPharmaceutical PreparationsPublishingResearchResearch PersonnelResourcesSHetA2SourceSubmitochondrial ParticlesSuccinate DehydrogenaseSuccinate dehydrogenase (ubiquinone)TissuesUbiquinoneUnited States National Institutes of Healthcancer chemopreventiondensityinhibitor/antagonistoxidative damage
中文摘要
这个子项目是众多研究子项目之一
英文摘要
This subproject is one of many research subprojects utilizing the
resources provided by a Center grant funded by NIH/NCRR. The subproject and
investigator (PI) may have received primary funding from another NIH source,
and thus could be represented in other CRISP entries. The institution listed is
for the Center, which is not necessarily the institution for the investigator.
We have recently published our observation of the rapid effects of the lead Flex-Het compound, SHetA2, on mitochondrial density, membrane integrity, Cytochrome C release and ROS generation, all indicative of the intrinsic apoptosis pathway. More recently, we have observed that Flex-Hets are potent, uncompetitive inhibitors of mitochondrial electron transport chain complex I and also inhibitors of complex II. Since few inhibitors of both complex I and II are know at present, in the first part of this proposal we will further examine the effect of Flex-Het drugs on succinate dehydrogenase and full ubiquinone dependent succinate:ubiquinone oxidoreductase activity. However mitochondria targeting drugs may be a two-edged sword, ROS themselves are highly toxic to cells and mitochondria can gradually accumUlate oxidative damage leading to mitochondrial collapse and cell death. In the second part of this proposal we propose to assess the possibility of mitochondrial injury in heart and liver cells following long-term Flex-Het treatment. Markers of impaired mitochondrial function such as decreased cellular ATP, decreased mitochondrial glutathione and decreased complex I activity will be measured in both cells, mitochondria and submitochondrial particles isolated from snap-frozen heart and liver tissue obtained from animals sacrificed following necropsy in an ongoing long-term colon cancer chemoprevention project evaluating ShetA2.
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EQUIPMENT FOR SOUTHWESTERN OKLAHOMA STATE UNIVERSITY
-
批准号:7960017
-
项目类别:
-
资助金额:$1.43万
-
财政年份:2009
-
负责人:KELLY J WILLIAM
-
依托单位:
EFFECTS OF FLEX-HETS ON CANCER CELL METABOLISM: NADH OXIDOREDUCTASE INHIBITION
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批准号:7960035
-
项目类别:
-
资助金额:$7.62万
-
财政年份:2009
-
负责人:KELLY J WILLIAM
-
依托单位:
EQUIPMENT FOR SOUTHWESTERN OKLAHOMA STATE UNIVERSITY
-
批准号:7725095
-
项目类别:
-
资助金额:$1.3万
-
财政年份:2008
-
负责人:KELLY J WILLIAM
-
依托单位:
EFFECTS OF FLEX-HETS ON CANCER CELL METABOLISM: NADH OXIDOREDUCTASE INHIBITION
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批准号:7725113
-
项目类别:
-
资助金额:$6.92万
-
财政年份:2008
-
负责人:KELLY J WILLIAM
-
依托单位:
国内基金
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