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翼状胬肉中的氧化性DNA损伤

Oxidative DNA damage in pterygium.

作者信息

Tsai Yi-Yu, Cheng Ya-Wen, Lee Huei, Tsai Fuu-Jen, Tseng Sung-Huei, Lin Chien-Lin, Chang Kong-Chao

机构信息

Department of Ophthalmology, China Medical University Hospital and Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.

出版信息

Mol Vis. 2005 Jan 25;11:71-5.

Abstract

PURPOSE

Epidemiological evidence suggests that UV irradiation plays the most important role in pterygial formation. The noxious effects of UV irradiation are either directly by a UV phototoxic effect or indirectly by formation of radical oxygen species (ROS). ROS are very harmful to cells, because they injure cellular DNA, proteins, and lipids (called oxidative stress). Among numerous types of oxidative DNA damage, the formation of 8-hydroxydeoxyguanosine (8-OHdG) presents only a minor fraction of UV induced DNA damage, but it is a ubiquitous marker of oxidative stress. If pterygium is related to UV, we surmised oxidative stress exists in pterygium. To provide the molecular evidence of UV radiation, 8-OHdG was detected in pterygium. Moreover, human 8-oxoguanine glycosylase (hOGG1) is the key component responsible for the removal of 8-OHdG. To determine whether the hOGG1 was expressed in pterygium, this enzyme was also evaluated.

METHODS

Immunohistochemical staining using a monoclonal antibody to 8-OHdG and hOGG1 were performed on 52 pterygial specimens and 6 normal conjunctiva.

RESULTS

There were 12 (23.1%) pterygial specimens positive for 8-OHdG staining, limited to the nuclei of the epithelial layer. No substantial staining was visible in the subepithelial fibrovascular layers. In pterygium with 8-OHdG staining, there were 4 (4/11, 36.4%) specimens with hOGG1 expression. However, in pterygium without 8-OHdG staining, there were only 3 (3/41, 7.3%) specimens with hOGG1 expression. hOGG1 expression was significantly associated with 8-OHdG positive staining. All normal controls were negative for 8-OHdG and hOGG1 staining.

CONCLUSIONS

Our study demonstrated for the first time 8-OHdG in pterygium, which represented oxidative stress in pterygium. The increased level of 8-OHdG in pterygium is not due to decreased expression of hOGG1, while increased levels of 8-OHdG induced the expression of hOGG1.

摘要

目的

流行病学证据表明紫外线照射在翼状胬肉形成中起最重要作用。紫外线照射的有害影响要么直接通过紫外线光毒性作用,要么间接通过活性氧(ROS)的形成。ROS对细胞非常有害,因为它们会损伤细胞DNA、蛋白质和脂质(称为氧化应激)。在众多类型的氧化性DNA损伤中,8-羟基脱氧鸟苷(8-OHdG)的形成仅占紫外线诱导的DNA损伤的一小部分,但它是氧化应激的普遍标志物。如果翼状胬肉与紫外线有关,我们推测翼状胬肉中存在氧化应激。为了提供紫外线辐射的分子证据,在翼状胬肉中检测了8-OHdG。此外,人8-氧代鸟嘌呤糖基化酶(hOGG1)是负责去除8-OHdG的关键成分。为了确定hOGG1是否在翼状胬肉中表达,也对这种酶进行了评估。

方法

对52例翼状胬肉标本和6例正常结膜进行了使用抗8-OHdG和hOGG1单克隆抗体进行的免疫组织化学染色。

结果

有12例(23.1%)翼状胬肉标本8-OHdG染色呈阳性,仅限于上皮层细胞核。上皮下纤维血管层未见明显染色。在8-OHdG染色阳性的翼状胬肉中,有4例(4/11,36.4%)标本有hOGG1表达。然而,在8-OHdG染色阴性的翼状胬肉中,仅有3例(3/41,7.3%)标本有hOGG1表达。hOGG1表达与8-OHdG阳性染色显著相关。所有正常对照8-OHdG和hOGG1染色均为阴性。

结论

我们的研究首次在翼状胬肉中证实了8-OHdG,它代表翼状胬肉中的氧化应激。翼状胬肉中8-OHdG水平升高并非由于hOGG1表达降低,而8-OHdG水平升高诱导了hOGG1的表达。

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