PUBLICATION
Bisphenol A exposure under metabolic stress induces accelerated cellular senescence in vivo in a p53 independent manner
- Authors
- Soundararajan, A., Yoganantharajah, P., Raghavan, S., Mohan, V., Balasubramanyam, M., Gibert, Y.
- ID
- ZDB-PUB-190801-6
- Date
- 2019
- Source
- The Science of the total environment 689: 1201-1211 (Journal)
- Registered Authors
- Gibert, Yann
- Keywords
- Apoptosis, Endocrine disruptor, Retinoblastoma 1, Zebrafish embryos, p15
- MeSH Terms
-
- Animals
- Benzhydryl Compounds/toxicity*
- Cellular Senescence/genetics*
- Embryo, Nonmammalian/physiology
- Endocrine Disruptors/toxicity*
- Phenols/toxicity*
- Stress, Physiological
- Tumor Suppressor Protein p53/genetics*
- Tumor Suppressor Protein p53/metabolism
- Water Pollutants, Chemical/toxicity*
- Zebrafish/embryology
- Zebrafish/genetics
- Zebrafish/physiology*
- Zebrafish Proteins/genetics*
- Zebrafish Proteins/metabolism
- PubMed
- 31358486 Full text @ Sci. Total Environ.
Citation
Soundararajan, A., Yoganantharajah, P., Raghavan, S., Mohan, V., Balasubramanyam, M., Gibert, Y. (2019) Bisphenol A exposure under metabolic stress induces accelerated cellular senescence in vivo in a p53 independent manner. The Science of the total environment. 689:1201-1211.
Abstract
Senescence is an irreversible process that is a characteristic of age-associated disease like Type 2 diabetes (T2D). Bisphenol-A (BPA), one of the most common endocrine disruptor chemicals, received special attention in the development of insulin resistance and T2D. To understand the role played by BPA in cellular senescence under metabolic stress, zebrafish embryos were exposed to BPA in the absence and presence of hyperglycaemia. Transcriptional levels of the senescence markers p15, p53, Rb1 and β-galactosidase were increased when BPA was combined with metabolic stress. In addition, zebrafish embryos that were exposed to combination of hyperglycaemia and BPA exhibited increased levels of apoptosis. However, cellular senescence remained induced by a combination of hyperglycaemia and BPA exposure even in the absence of a translated p53 protein suggesting that senescence is primarily independent of it but dependent on the p15-Rb1 pathway under our experimental conditions. To confirm that our results hold true in adult mammalian tissues, we validated our embryonic experiments in an adult mammalian metabolic model of skeletal muscle cells. Our work reveals a novel and unique converging role of senescence and apoptosis axis contributing to glucose dyshomeostasis. Thus, we conclude that BPA exposure can exacerbate existing metabolic stress to increase cellular senescence that leads to aggravation of disease phenotype in age-associated diseases like type 2 diabetes.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping