Bisphenol A regulates cytochrome P450 1B1 through miR-27b-3p and induces carp lymphocyte oxidative stress leading to apoptosis. Issue 102 (July 2020)

• Record Type: Journal Article
• Authors: Liu, Qingqing; Wang, Wei; Zhang, Yiming; Cui, Yuan; Xu, Shiwen; Li, Shu
• Is Part Of: Fish & shellfish immunology. Issue 102(2020)
• Page Start: 489
• Page End: 498
• Publication Date: 2020-07
• Subjects: Bisphenol A -- miR-27b-3p -- CYP1B1 -- Oxidative stress -- Apoptosis; Fishes -- Immunology -- Periodicals; Shellfish -- Immunology -- Periodicals; Poissons -- Immunologie -- Périodiques; Crustacés -- Immunologie -- Périodiques; 571.9617
• DOI: 10.1016/j.fsi.2020.05.009
• Languages: English
• ISSNs: 1050-4648

Abstract

Abstract: Bisphenol A (BPA) is an industrial raw material widely used in water bottles, medical devices and food packaging, and is now ubiquitous in the environment. However, the effects of BPA on the toxicity of fish lymphocytes and the roles of microRNA (miRNA) in this process remain poorly understood. To explore the mechanism, we exposed carp spleen lymphocytes to BPA of 1, 5 and 10 nM for 24 h. The results showed that BPA induced carp lymphocyte apoptosis. BPA inhibited the expression of miR-27b-3p mRNA, thereby increasing the expression of cytochrome P450 1B1, increasing ROS levels, inhibiting SOD, CAT, GSH-PX activity, GSH content, promoting the accumulation of NOS and MDA. At the same time, BPA activated the mitochondrial apoptosis pathway, inhibited the expression of BCL-2, and promoted the expression of CytC, BAX, Caspase-9 and Caspase-3. Dual luciferase reporter system showed CYP1B1 is the target genes of miR-27b-3p and negatively regulated by it. Overexpression of miR-27b-3p partially reversed oxidative stress and apoptosis of carp spleen lymphocytes induced by BPA stimulation. Taken together, BPA exposure can target up regulate CYP1B1 expression by down regulating miR-27b-3p expression, thus causing oxidative stress and inducing apoptosis of carp spleen lymphocytes through mitochondrial pathway. Our study will provide theoretical basis for immunotoxicology mechanism research and environmental protection of BPA in fish. Graphical abstract: Image 1 Highlights: CYP1B1 is a target gene of miR-27b-3p in fish. BPA exposure alters the expression of miR-27b-3p and CYP1B1 in carp lymphocytes, thereby inducing oxidative stress. BPA exposure induces lymphocyte apoptosis through mitochondrial pathway. Overexpress miR-27b-3p can partially reversed oxidative stress and apoptosis of lymphocytes induced by BPA stimulation.