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生长激素过表达改变了肌肉中抗氧化酶的表达,并增加了老年斑马鱼的脊柱弯曲度。

GH overexpression modifies muscle expression of anti-oxidant enzymes and increases spinal curvature of old zebrafish.

机构信息

PPGCF-FAC, Instituto de Ciências Biológicas, Universidade Federal do Rio Grande, Brazil.

出版信息

Exp Gerontol. 2010 Jun;45(6):449-56. doi: 10.1016/j.exger.2010.03.012. Epub 2010 Mar 23.

Abstract

Growth hormone (GH) excess causes an increment in the metabolic rate and in reactive oxygen species generation, which accelerate the ageing process in mammals. Considering that there is no information on this subject in fish, the aim of the present study was to evaluate the excess GH effect on senescence in a zebrafish (Danio rerio) transgenic model. In order to reach this objective, we analyzed the phenotype of spinal curvature and expression of genes related to the anti-oxidant defense system and myogenesis in muscle of 8 and 30 months old GH-transgenic males. Gene expression analyses revealed that both superoxide dismutase isoforms were down-regulated only in 30 months old animals, while glutamate cysteine ligase was down-regulated in GH-transgenic zebrafish. Acceleration of the spinal curvature and a reduction in the expression of miogenin at both ages and MyoD in the old fish were also observed. Although neurolipofuscin accumulation was not significant in GH-transgenic zebrafish, the estimation of maximum longevity based on the von Bertalanffy growth function was significantly lower in this group. The results obtained here indicate that GH overexpression reduces the transcription of anti-oxidant defense system and myogenesis-related genes, which probably accelerates senescence in the zebrafish transgenic model used.

摘要

生长激素(GH)过多会导致代谢率增加和活性氧生成增加,从而加速哺乳动物的衰老过程。由于鱼类在这方面没有信息,本研究的目的是评估过量 GH 对斑马鱼(Danio rerio)转基因模型衰老的影响。为了达到这个目的,我们分析了脊柱弯曲的表型以及与抗氧化防御系统和肌肉生成相关的基因在 8 个月和 30 个月大的 GH 转基因雄性中的表达。基因表达分析表明,两种超氧化物歧化酶同工型仅在 30 个月大的动物中下调,而谷氨酸半胱氨酸连接酶在 GH 转基因斑马鱼中下调。在两个年龄阶段,脊柱弯曲加速和肌生成基因 miogenin 的表达减少,以及老年鱼中的 MyoD 减少也被观察到。尽管神经脂褐素在 GH 转基因斑马鱼中的积累不显著,但基于 von Bertalanffy 生长函数的最大寿命估计在该组中显著降低。这里获得的结果表明,GH 过表达降低了抗氧化防御系统和与肌肉生成相关的基因的转录,这可能加速了所使用的斑马鱼转基因模型的衰老。

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