长期对甲基的亚致命暴露会延长斑马发育中的端粒
Rachel L Davis1, Samuel D Mason2, Christian Wake3
1Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United States of America; Biology Department, William & Mary, Williamsburg, VA, United States of America.
Environmental pollution (Barking, Essex : 1987)
|September 23, 2025
概括
年轻鸟类的慢性甲基 (MeHg) 暴露导致了更长的端粒,这表明细胞过程类似于癌症的发展. 这表明端粒维护可能独立于应激下细胞增殖.
科学领域:
- 环境毒理学环境毒理学
- 遗传学 是一个遗传学.
- 细胞生物学 细胞生物学
背景情况:
- 甲基 (MeHg) 是一种普遍存在的环境污染物,通过活性氧物种 (ROS) 引起DNA损伤.
- 端粒保护染色体,但易受氧化应激和缩短的影响.
- 慢性ROS诱导剂对端粒长度的体内影响尚不清楚.
研究的目的:
- 为了研究多代,次致命的甲基暴露对生命早期端粒动态的影响.
- 为了探索 telomere 长度变化背后的机制在慢性氧化应激 in vivo.
主要方法:
- 斑马青在几代人中连续暴露在1.2mg/kgMeHg的食度中.
- 在性成熟时,测量了各种组织 (血液,大脑,肝脏,脏,肺) 的相对端粒长度.
- 分析了PCNA和β-catenin的蛋白质表达,以及骨髓的转录组分析.
主要成果:
- 暴露于MeHg导致性成熟时多个组织的相对端粒显著更长.
- 没有发现跨代更长端粒的选择证据.
- 在暴露于MeHg的年轻鸟类中观察到β-catenin表达的增加,而PCNA水平保持不变. 转录组学显示了瘤,炎症和细胞循环途径的改变.
结论:
- 长期暴露于甲基会促进端粒的延长或维持,而不依赖于增殖,可能是通过Wnt信号.
- 观察到的细胞变化类似于瘤发生,这表明慢性压力,端粒维护和复制性不朽之间存在联系.
相关概念视频
02:41Lethal Alleles
Agouti: A Lethal Allele
Lucien Cuénot discovered lethal alleles in 1905 while studying the inheritance of coat color in mice. The agouti gene is responsible for the color of the coat in mice. This gene codes for an agouti-signaling protein, which is responsible for melanin distribution in mammals. The wild-type allele gives rise to gray-brown coat color in mice, while the mutant allele gives rise to yellow coat color. In addition to coat color, the agouti gene is associated with the yellow...
Lucien Cuénot discovered lethal alleles in 1905 while studying the inheritance of coat color in mice. The agouti gene is responsible for the color of the coat in mice. This gene codes for an agouti-signaling protein, which is responsible for melanin distribution in mammals. The wild-type allele gives rise to gray-brown coat color in mice, while the mutant allele gives rise to yellow coat color. In addition to coat color, the agouti gene is associated with the yellow...
02:15Replicative Cell Senescence
Replicative cell senescence is a property of cells that allows them to divide a finite number of times throughout the organism's lifespan while preventing excessive proliferation. Replicative senescence is associated with the gradual loss of the telomere — short, repetitive DNA sequences found at the end of the chromosomes. Telomeres are bound by a group of proteins to form a protective cap on the ends of chromosomes. Embryonic stem cells express telomerase — an enzyme that adds the telomeric...
02:07Tumor Progression
Tumor progression is a phenomenon where the pre-formed tumor acquires successive mutations to become clinically more aggressive and malignant. In the 1950s, Foulds first described the stepwise progression of cancer cells through successive stages.
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
01:19Pigmentation
The color of the skin is influenced by a number of pigments, including melanin, carotene, and hemoglobin. Recall that melanin is produced by cells called melanocytes, which are found scattered throughout the stratum basale of the epidermis. The melanin is transferred to the keratinocytes via melanosomes.
Melanin occurs in two primary forms: eumelanin that provides black and brown pigment and pheomelanin that provides red color. Dark-skinned individuals produce more melanin than those with pale...
Melanin occurs in two primary forms: eumelanin that provides black and brown pigment and pheomelanin that provides red color. Dark-skinned individuals produce more melanin than those with pale...
01:30Skin Cancer
Skin cancer is a type of cancer that occurs when there is an abnormal growth of skin cells, usually triggered by damage to the DNA within the skin cells. It is primarily caused by exposure to ultraviolet (UV) radiation from the sun or artificial sources like tanning beds. Skin cancer is the most common type of cancer worldwide, and its incidence continues to rise.
Basal Cell Carcinoma (BCC): BCC is the most common type of skin cancer, accounting for about 80% of cases. It typically develops in...
Basal Cell Carcinoma (BCC): BCC is the most common type of skin cancer, accounting for about 80% of cases. It typically develops in...
01:07Teratogenicity
The ability of a drug to produce structural deformations and functional abnormalities in the developing embryo or the fetus is called teratogenicity, and the drug producing this effect is known as a teratogen. Teratogenic effects include stillbirth, miscarriage, intrauterine growth restriction, and neurocognitive delay. A teratogen may affect the embryo at different stages of development, which is important in determining the type and extent of the damage. During blastocyst formation, the early...