Blind cavefish and heat shock protein chaperones:: a novel role for hsp90α in lens apoptosis
Blind cavefish and heat shock protein chaperones:: a novel role for hsp90α in lens apoptosis
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DOI：
10.1387/ijdb.041874th
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发表时间：
2004-01-01
影响因子：
0.7
通讯作者：
Jeffery, WR
中科院分区：
文献类型：
--
作者：
Hooven, TA;Yamamoto, Y;Jeffery, WR
透镜凋亡在洞穴鱼眼退化中起着重要作用。热休克蛋白（hsps）可以调节细胞凋亡，因此，我们研究了组成性hsp70和hsp90表达与透镜细胞凋亡之间的关系。模式系统是墨西哥丽脂鲤，硬骨鱼物种组成的眼睛表面居住（表面鱼）的形式和许多盲目的洞穴居住（洞穴鱼）的形式。洞穴鱼胚胎中形成视原基，但随后它们经历透镜细胞凋亡、发育停滞和退化。本文分离了丽脂鲤hsp90和hsp70的DNA，并将其作为探针比较了在表层鱼和洞穴鱼发育过程中的基因表达。热休克蛋白90 β，编码两种热休克蛋白90亚型之一，不表达在表面鱼或洞穴鱼透镜，而热休克蛋白70表达在透镜的两种形式，这表明既不直接参与透镜凋亡。与此相反，热休克蛋白90 α，另一种热休克蛋白90亚型，表达在洞穴鱼，但不是表面鱼透镜。在3个会聚型洞穴鱼群体中，Hsp90 α的表达在透镜凋亡开始前不久达到峰值，表明其与透镜凋亡密切相关。透镜中hsp90 β的缺失使我们能够使用格尔德霉素和根赤霉素（hsp90分子伴侣功能的特异性抑制剂）来确定透镜细胞死亡是否需要hsp90 α的表达。这两种抑制剂阻断了洞穴鱼透镜中的TUNEL标记，表明hsp90 α是细胞凋亡所必需的。与它们对透镜的影响相反，这些抑制剂诱导表面表皮中的TUNEL标记，推测是由于对hsp90 β功能的影响，这意味着两种hsp90亚型在细胞存活中可能具有相反的作用。我们的结论是，热休克蛋白90 α在透镜细胞凋亡和洞穴鱼眼变性中发挥了新的作用。
Lens apoptosis plays a central role in cavefish eye degeneration. Heat shock proteins (hsps) can regulate apoptosis; therefore, we examined the relationship between constitutive hsp70 and hsp90 expression and lens apoptosis. The model system is Astyanax mexicanus, a teleost species consisting of an eyed surface-dwelling (surface fish) form and numerous blind cave-dwelling (cavefish) forms. Optic primordia are formed in the cavefish embryo but they subsequently undergo lens apoptosis, arrest in development and degenerate. Astyanax hsp90 and hsp70 DNAs were isolated to use as probes to compare gene expression during surface fish and cavefish development. Hsp90beta, which encodes one of two hsp90 isoforms, was not expressed in the surface fish or cavefish lens, whereas hsp70 was expressed in the lens of both forms, suggesting that neither is directly involved in lens apoptosis. In contrast, hsp90alpha, the other hsp90 isoform, was expressed in the cavefish but not the surface fish lens. Hsp90alpha expression peaked shortly before the beginning of lens apoptosis in three convergent cavefish populations, suggesting a close relationship with lens apoptosis. The absence of hsp90beta in the lens allowed us to use geldanamycin and radicicol, specific inhibitors of hsp90 chaperone function, to determine whether lens cell death requires hsp90alpha expression. Both inhibitors blocked TUNEL labeling in the cavefish lens, suggesting that hsp90alpha is required for apoptosis. In contrast to their effects on the lens, these inhibitors induced TUNEL labeling in the surface epidermis, presumably due to effects on hsp90beta function, implying that the two-hsp90 isoforms may have contrasting roles in cell survival. We conclude that hsp90alpha plays a novel role in lens apoptosis and cavefish eye degeneration.