Protein Oxidation in Skin Cells by Tan Bed Irradiation

晒黑床辐射对皮肤细胞中蛋白质的氧化

• 批准号: 7269563
• 负责人: James Douglas Hoerter
• 金额: $ 5.64万
• 依托单位: FERRIS STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-08-01 至 2007-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7269563
• 关键词: DNA damage; antioxidants; enzyme activity; fibroblasts; free radical oxygen; gel electrophoresis; keratinocyte; oxidative stress; pathologic process; posttranslational modifications; selenium; skin neoplasms; solar radiation; ultraviolet radiation; western blottings

DESCRIPTION (provided by applicant): The long-term objective is to identify the specific cellular mechanisms involved in the damage, protection and recovery from UVA (290-320 nm) and UVB (320-400 nm) irradiation. Increased exposure to solar UVA/UVB irradiation is related to the rise in skin cancer. Human health is affected by increased UVA/UVB due to (1) the erosion of the stratospheric ozone layer; (2) more time spent outdoors in recreational activities, and (3) increased use of tanning beds. On an average day in the United States, more than one million people visit a tanning salon and expose themselves to UVA radiation with intensity up to 10 times higher than sunlight depending on the type of tanning bed used. During the last 3 years, use of tanning beds increased from 7% among 14-year-old girls to 16% by age 15, and 35% by age 17. Studies show a connection between the increased use of tanning beds and a higher incidence of skin cancer. Approximately 7,500 deaths will be attributed to melanoma in 2003. The combination of high intensity UVA tanning bed irradiation and solar UV irradiation significantly increases tumor incidence and impairs the ability of cells to repair DNA damage. Highly reactive oxygen radicals mediate the damaging effects of UVA irradiation. Proteins are one of the major targets of reactive oxygen radicals. Using human keratinocytes and fibroblasts, a specific aim of this study will be to quantify the extent of protein oxidation after standard doses of irradiation delivered under tanning bed vs. solar irradiation intensity (fluence levels). Changes in activity levels of key antioxidant enzymes will be correlated with protein oxidation. Selenium, known to induce genes in oxidative defense, will be used to determine its potential for reducing UVA-induced oxidative modification of proteins. The research methods will include protein gel electrophoresis and western blots to identify and quantify oxidized proteins under a variety of irradiation conditions to determine if changes in intensity, dose or exposure cycles can decrease protein oxidation. This research is significant because it will help to develop strategies to minimize the harmful effects of increased use of tanning beds despite the published warnings of their health hazards; it will contribute to the development of photo-protective and photo-therapeutic strategies in medicine. This research will have an impact on the undergraduate teaching environment by providing multiple research opportunities for students, who are preparing for careers in the health-related professions, to develop critical thinking skills by designing and conducting experiments, collecting data and interpreting their significance to human health.

描述（由申请人提供）： 长期目标是确定 UVA（290-320 nm）和 UVB（320-400 nm）照射造成的损伤、保护和恢复所涉及的特定细胞机制。暴露于太阳 UVA/UVB 照射的增加与皮肤癌的增加有关。由于以下原因，人类健康受到 UVA/UVB 增加的影响：(1) 平流层臭氧层的侵蚀； (2) 更多的时间花在户外娱乐活动上，(3) 增加日光浴床的使用。在美国，平均每天有超过一百万人光顾晒黑沙龙，并暴露在 UVA 辐射下，其强度高达阳光的 10 倍，具体取决于所使用的晒黑床的类型。在过去 3 年里，日光浴床的使用率从 14 岁女孩的 7% 增加到 15 岁时的 16%，到 ​​17 岁时增加到 35%。研究表明，日光浴床的使用增加与皮肤癌发病率升高之间存在联系。 2003 年，大约有 7,500 人死于黑色素瘤。高强度 UVA 日光浴床照射和太阳紫外线照射的结合显着增加了肿瘤发生率，并损害了细胞修复 DNA 损伤的能力。高活性氧自由基介导 UVA 照射的破坏作用。蛋白质是活性氧自由基的主要目标之一。使用人类角质形成细胞和成纤维细胞，本研究的具体目的是量化在晒黑床下进行标准剂量照射与太阳照射强度（注量水平）后蛋白质氧化的程度。关键抗氧化酶活性水平的变化将与蛋白质氧化相关。硒已知可诱导氧化防御基因，将用于确定其减少 UVA 诱导的蛋白质氧化修饰的潜力。研究方法将包括蛋白质凝胶电泳和蛋白质印迹，以识别和量化各种辐照条件下的氧化蛋白质，以确定强度、剂量或暴露周期的变化是否可以减少蛋白质氧化。这项研究意义重大，因为它将有助于制定策略，最大限度地减少增加使用日光浴床的有害影响，尽管已发布了关于日光浴床健康危害的警告；它将有助于医学上光保护和光治疗策略的发展。这项研究将为准备从事健康相关专业职业的学生提供多种研究机会，通过设计和进行实验、收集数据并解释其对人类健康的重要性来培养批判性思维技能，从而对本科教学环境产生影响。

项目成果

Effect of UVA fluence rate on indicators of oxidative stress in human dermal fibroblasts.

• DOI: 10.7150/ijbs.4.63
• 发表时间: 2008-02-19
• 期刊: International journal of biological sciences
• 影响因子: 9.2
• 作者: Hoerter JD;Ward CS;Bale KD;Gizachew AN;Graham R;Reynolds J;Ward ME;Choi C;Kagabo JL;Sauer M;Kuipers T;Hotchkiss T;Banner N;Chellson RA;Ohaeri T;Gant L;Vanderhill L
• 通讯作者: Vanderhill L