Bisphenol A exposure under metabolic stress induces accelerated cellular senescence in vivo in a p53 independent manner

Avinash, S and Yoganantharajah, P and Srividhya, R and Mohan, V and Balasubramanyam, M and Gibert, Y (2019) Bisphenol A exposure under metabolic stress induces accelerated cellular senescence in vivo in a p53 independent manner. Science of The Total Environment, 689 . p. 1201. ISSN 00489697

Restricted to MDRF users only. Others may ->



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.

Item Type:Article
Official URL/DOI:
Uncontrolled Keywords:Zebrafish embryos; Endocrine disruptor; Apoptosis; p15; Retinoblastoma 1
Subjects:Biochemistry,Cell and Molecular Signalling
Divisions:Department of Cell and Molecular Biology
Department of Diabetology
ID Code:1135
Deposited By:surendar radha
Deposited On:06 Sep 2019 13:48
Last Modified:06 Sep 2019 13:48

Repository Staff Only: item control page