Gene Expression Of Hsc70 And Hsp70 In Mammals
Gene Expression Of Hsc70 And Hsp70 In Mammals
批准号:
6667886
负责人:
Stanley I. Rapoport
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$0.0万
依托单位国家:
美国
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财政年份:
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资助国家:
美国
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未结题
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中文摘要
热休克基因,包括热休克70基因家族的成员,是高度保守的,一些成员在环境或生理压力下被诱导。在热休克70家族中,热休克同源基因(Hsc70)在非应激脑组织中表达水平较高,在应激状态下的脑组织中表达水平较高。该家族的可诱导成员(HSP70)在非应激鼠脑中的表达水平很低,在应激后瞬时高水平表达。相比之下,HSP70在所有被检测的人脑中的表达水平要高得多,即使是在没有死亡压力记录的突然和意外死亡的人中也是如此。HSP70的高水平表达可能是人脑的一个特征。或者,死后间隔(PMI)和/或死前应激源都可能影响HSP70基因家族在人脑中的表达。在PMI研究中,hsc70和hsp70蛋白被发现在人脑中至少稳定27小时。即使消除了死前应激(病历中发现的发热、缺氧、昏迷等),猝死人脑中HSP70蛋白的组成水平仍比应激啮齿动物高出数倍。这些结果有力地表明,HSP70在人脑中的结构性表达确实比啮齿类动物的脑中高出许多倍。非人灵长类动物的大脑已经有了很好的特征,它的生长和发育与人类大脑中看到的相似。猴子模型的使用将消除处理人体组织、死后间隔(PMI)以及死前压力的固有问题。在非人灵长类动物脑中,hsc70和hsp70基因的表达水平与人类相似。与在人类中一样,HSP70蛋白结构性地高水平表达,仅比hsc70蛋白水平低几倍。HSP70的高表达可能是灵长类特有的,也可能与寿命有关。
英文摘要
Heat shock genes, including members of the heat shock 70 gene family, are highly conserved and some members are induced in response to environmental or physiological stress. In the heat shock 70 family, the heat shock cognate (hsc70) gene is expressed at high constitutive levels in non-stressed brain and at higher levels in stressed brain in all species examined so far. Inducible members of the family (hsp70) are expressed at very low levels in non-stressed rodent brain, and transiently expressed at high levels following stress. In contrast, hsp70 is expressed at much higher levels in all human brains assayed, even in persons who died suddenly and unexpectedly, with no documented agonal stress. High levels of expression of hsp70 could be a characteristic of human brain. Alternatively, post mortem interval (PMI), and/or premortem stressors could each be affecting the expression of the hsp70 gene family in human brain. In PMI studies, hsc70 and hsp70 protein was found to be stable for at least 27 hours in human brain. Even when premortem stress was eliminated (fever, hypoxia, coma etc. found in medical records) the constitutive levels of hsp70 protein were still several fold higher in sudden death human brain than that seen in stressed rodent. These results strongly suggest that constitutive expression of hsp70 is indeed many fold higher in human than in rodent brain. The non-human primate brain has been well characterized and its growth and development parallels that seen in human brain. The use of the monkey model would eliminate the inherent problems of working with human tissue, post mortem interval (PMI) as well as premortem stresses. In non-human primate brain, hsc70 and hsp70 mRNA levels were similar to those in humans. As in humans, hsp70 protein was constitutively expressed at high levels, only several fold less than the levels of hsc70 protein. The high hsp70 expression could be primate specific or it could be related to life span.
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