Differential induction of proto-oncogene expression and cell death in ocular tissues following ultraviolet irradiation of the rat eye
Differential induction of proto-oncogene expression and cell death in ocular tissues following ultraviolet irradiation of the rat eye
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大鼠眼紫外线照射后眼组织中原癌基因表达和细胞死亡的差异诱导
DOI：
10.1136/bjo.83.2.225
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发表时间：
1999
影响因子：
4.1
通讯作者：
F. Gillardon
中科院分区：
文献类型：
--
作者：
H. Wickert;K. Zaar;A. Grauer;Markus R. John;M. Zimmermann;F. Gillardon
背景/目的紫外线照射培养的哺乳动物细胞可激活不同原癌基因的转录，其中包括fos/jun家族成员，该家族在细胞增殖和分化中起重要作用。为了研究紫外线照射后眼细胞体内原癌基因的表达，我们分析了角膜、晶状体和视网膜中JunB、JunD和Egr-1的表达。此外，已知紫外线辐射可诱导受照射细胞发生多营养事件，包括生长停滞、炎症甚至细胞死亡。为了确定细胞死亡的类型，例如，凋亡与坏死，紫外线照射大鼠眼睛的切片进一步检查细胞死亡和DNA断裂的不同超微结构形态。方法麻醉大鼠眼暴露于1.5 J/cm2紫外线照射下（280 ~ 380 nm）。分别于照射后6和16 h灌注动物，取去核球组织切片进行光镜和电镜观察。结果在对照条件下，Jun B在角膜上皮的大量浅表细胞和分散的基底细胞中均有组成性表达。尽管在整个实验过程中，角膜基质和内皮细胞均为JunB阴性，但在紫外线照射后，JunB在角膜上皮基底细胞层的许多细胞中的表达大量上调。相比之下，Egr-1仅在晶状体上皮中表达，在对照条件下仅显示微弱的表达模式。然而，紫外线照射后，Egr-1表达增加，因此在紫外线照射数小时后，晶状体上皮可发现许多Egr-1阳性细胞。JunD在视网膜神经节细胞层和内核层的单细胞中均有表达，这种表达模式在紫外线照射后没有改变。在细胞死亡类型方面，对照眼角膜上皮的散在浅表细胞中仅偶有凋亡的特征。然而，在紫外线照射后，大鼠角膜间质和上皮均可见凋亡和TUNEL阳性细胞的形态学迹象。相比之下，紫外线照射的晶状体上皮细胞表现出典型的坏死特征。在紫外线照射后，角膜内皮和视网膜未显示任何表明细胞死亡的形态学变化。结论每种原癌基因编码蛋白均以组织特异性的方式表达，紫外线照射对这些转录调控蛋白的表达模式有差异调节。这些蛋白的时空表达模式伴随着紫外线照射后角膜和晶状体中两种形态不同的细胞死亡。
BACKGROUND/AIMS Ultraviolet (UV) irradiation of mammalian cells in culture evokes the transcriptional activation of different proto-oncogenes, among them members of the fos/jun family which are known to play an important role in cell proliferation and differentiation. To investigate in vivo UV induced proto-oncogene expression of irradiated ocular cells, the expression of JunB, JunD, and Egr-1 was analysed in the cornea, lens, and retina. Furthermore, UV radiation is known to induce pleiotrophic events in irradiated cells which include growth arrest, inflammation, and even cell death. In order to determine the type of cell death—for example, apoptosis versus necrosis, sections of UV irradiated rat eyes were further examined for distinct ultrastructural morphology of cell death and DNA fragmentation. METHODS Eyes of anaesthetised rats were exposed to 1.5 J/cm2 of ultraviolet radiation (280–380 nm). Animals were perfused 6 and 16 hours after irradiation and tissue sections of enucleated bulbi were processed for light and electron microscopy. RESULTS Under control conditions, Jun B was constitutively expressed in numerous superficial cells but also in scattered basal cells of the corneal epithelium. After UV exposure JunB expression was massively upregulated in many cells of the basal cell layers of the corneal epithelium, although during the entire experiment, both the corneal stroma and endothelium were JunB negative. In contrast, Egr-1 was expressed exclusively in lens epithelium showing only a faint expression pattern under control conditions. However, Egr-1 expression increased after UV exposure, so that many Egr-1 positive cells of the lens epithelium could be found several hours after UV illumination. JunD was expressed in single cells of both the ganglion cell layer and the inner nuclear layer of the retina, a pattern of expression which did not change after UV exposure. Regarding the type of cell death, features of apoptosis were only occasionally present in scattered superficial cells of the corneal epithelium of control eyes. After UV exposure, however, morphological signs of apoptosis and TUNEL positive cells were visible both in the stroma and epithelium of the rat cornea. In contrast, UV irradiated lens epithelial cells exhibited features typical of necrosis. The corneal endothelium and the retina did not show any indications of morphological changes indicative of cell death after UV irradiation. CONCLUSION Each proto-oncogene encoded protein was found to be expressed in a tissue specific manner and UV irradiation differentially modulates the expression pattern of these transcriptional regulatory proteins. This temporospatial expression pattern of these proteins is accompanied by two morphologically distinct types of cell death in the cornea and lens after UV irradiation.
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影响因子：
3.4
作者：
SPECTOR, A;WANG, GM;KLEIMAN, NJ
通讯作者：
KLEIMAN, NJ
影响因子：
3.4
作者：
SPECTOR, A;WANG, GM;KUSZAK, JR
通讯作者：
KUSZAK, JR
Egr-1 在紫外线照射后细胞存活中的生物学作用。
DOI：
--
发表时间：
1995
期刊：
Oncogene.
影响因子：
--
作者：
Huang,RP;Adamson,ED
通讯作者：
Adamson,ED
培养晶状体近紫外线辐射后白内障发生的机制。
影响因子：
2
作者：
Hightower,K;McCready,J
通讯作者：
McCready,J
影响因子：
3.4
作者：
LI, WC;KUSZAK, JR;SPECTOR, A
通讯作者：
SPECTOR, A