PHOTORECEPTOR RETINOL DEHYDROGENASES AND VISION
光感受器视黄醇脱氢酶与视力
基本信息
- 批准号:7959977
- 负责人:
- 金额:$ 21.91万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2009
- 资助国家:美国
- 起止时间:2009-07-01 至 2010-06-30
- 项目状态:已结题
- 来源:
- 关键词:4 hydroxynonenalAlcoholsAldehydesApoptosisBlindnessCell Culture TechniquesCell DeathCellsComputer Retrieval of Information on Scientific Projects DatabaseCultured CellsFundingGrantIn VitroInstitutionKnockout MiceLeadLeber&aposs amaurosisLightLipid PeroxidationMeasuresMediatingMentorsMicrosomesMusMutationOklahomaOxidative StressPatientsPhotoreceptorsProteinsResearchResearch PersonnelResourcesRetinaRetinalRetinal DystrophyRetinol dehydrogenaseSourceToxic effectUnited States National Institutes of HealthVisionVision researchadductearly onsetin vivopreventprotective effectresearch studytreatment strategy
项目摘要
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 hypothesized that RDH12 protects photoreceptors from toxic medium-chain aldehydes produced during oxidative stress. If not cleared, these aldehydes lead to apoptosis. We investigated if RDH12 could detoxify 4-hydroxynonenal (4-HNE), one of the most toxic products of lipid peroxidation, released in cells during oxidative stress.
We compared the toxicity of 4-HNE in presence and absence of RDH12, in vitro, in cultured cells, and in vivo. The toxicity of 4-HNE was measured by quantification of 4-HNE-protein adducts and cell death. In vitro and cell culture experiments were performed with exogenous 4-HNE. Wild-type and Rdh12 knockout mice were subjected to light to induce the release of endogenous 4-HNE in photoreceptors.
RDH12 is protective against the formation of adducts in isolated retinal microsomes, cultured cells, and in retinas of mice subjected to dim cyclic light. Wild type RDH12 also significantly protects against 4-HNE-induced cell death in cultured cells. A mutation of RDH12 associated with Leber congenital amaurosis induces the loss of its protective function. RDH12 significantly protects mouse photoreceptors against bright light-induced cell death.
The protective effect of RDH12 is due to reduction of 4-HNE to non-toxic alcohol, preventing adduct formation and apoptosis. Defective clearance of 4-HNE and other aldehydes could mediate the early onset vision loss and retinal dystrophy associated with mutations in RDH12 in patients with Leber congenital amaurosis. In this case, an adapted strategy for treatment would be to use molecules such as carcinine that have the ability to enter the cells and scavenge toxic aldehydes.
这个子项目是许多研究子项目中的一个
由NIH/NCRR资助的中心赠款提供的资源。子项目和
研究者(PI)可能从另一个NIH来源获得了主要资金,
因此可以在其他CRISP条目中表示。所列机构为
研究中心,而研究中心不一定是研究者所在的机构。
我们假设RDH 12保护光感受器免受氧化应激过程中产生的有毒中链醛的伤害。如果不清除,这些醛会导致细胞凋亡。我们研究了RDH 12是否可以解毒4-羟基壬烯醛(4-HNE),这是氧化应激期间细胞中释放的最具毒性的脂质过氧化产物之一。
我们比较了在存在和不存在RDH 12的情况下,在体外,在培养的细胞中和在体内的4-HNE的毒性。通过定量4-HNE-蛋白质加合物和细胞死亡来测量4-HNE的毒性。用外源性4-HNE进行体外和细胞培养实验。野生型和Rdh 12敲除小鼠经受光以诱导光感受器中内源性4-HNE的释放。
RDH 12在分离的视网膜微粒体、培养的细胞和经历昏暗的周期性光的小鼠视网膜中对加合物的形成具有保护作用。野生型RDH 12还显著地保护培养的细胞免于4-HNE诱导的细胞死亡。与Leber先天性黑蒙相关的RDH 12突变导致其保护功能丧失。RDH 12显著保护小鼠光感受器免受强光诱导的细胞死亡。
RDH 12的保护作用是由于4-HNE还原为无毒的醇,防止加合物形成和细胞凋亡。4-HNE和其他醛类的清除缺陷可能介导与Leber先天性黑蒙患者RDH 12突变相关的早发性视力丧失和视网膜营养不良。在这种情况下,一种适应性的治疗策略是使用能够进入细胞的分子,如癌碱和有毒的醛。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Anne Kasus-Jacobi其他文献
Anne Kasus-Jacobi的其他文献
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{{ truncateString('Anne Kasus-Jacobi', 18)}}的其他基金
Wound healing mechanisms modulated by novel antimicrobial Peptides
新型抗菌肽调节伤口愈合机制
- 批准号:
9182311 - 财政年份:2016
- 资助金额:
$ 21.91万 - 项目类别:
PHOTORECEPTOR RETINOL DEHYDROGENASES AND VISION
光感受器视黄醇脱氢酶与视力
- 批准号:
8168350 - 财政年份:2010
- 资助金额:
$ 21.91万 - 项目类别:
Detoxification Role of Retinol Dehydrogenases RDH11 and RDH12
视黄醇脱氢酶 RDH11 和 RDH12 的解毒作用
- 批准号:
7530623 - 财政年份:2008
- 资助金额:
$ 21.91万 - 项目类别:
UNDERSTANDING THE ROLE OF RETINOL DEHYDROGENASES RDH11 AND RDH12 IN VISION
了解视黄醇脱氢酶 RDH11 和 RDH12 在视觉中的作用
- 批准号:
7720540 - 财政年份:2008
- 资助金额:
$ 21.91万 - 项目类别:
Detoxification Role of Retinol Dehydrogenases RDH11 and RDH12
视黄醇脱氢酶 RDH11 和 RDH12 的解毒作用
- 批准号:
7689187 - 财政年份:2008
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$ 21.91万 - 项目类别:
Structural Approach to Define New Functional Activities of Neutrophil Protein CAP37 in Neurodegenerative Diseases(Kasus-Jacobi)
定义中性粒细胞蛋白 CAP37 在神经退行性疾病中新功能活性的结构方法(Kasus-Jacobi)
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- 资助金额:
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