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苯并[a]芘暴露致栉孔扇贝造血损伤的潜在分子机制。

Potential molecular mechanism underlying the harmed haemopoiesis upon Benzo[a]pyrene exposure in Chlamys farreri.

机构信息

The Key Laboratory of Mariculture, Ministry of Education, Ocean University of China, Qingdao, 266003, PR China.

The Key Laboratory of Mariculture, Ministry of Education, Ocean University of China, Qingdao, 266003, PR China.

出版信息

Fish Shellfish Immunol. 2023 Oct;141:109032. doi: 10.1016/j.fsi.2023.109032. Epub 2023 Aug 26.

DOI:10.1016/j.fsi.2023.109032
PMID:37640119
Abstract

Benzo[a]pyrene (B[a]P), a ubiquitous contamination in the marine environments, has the potential to impact the immune response of bivalves by affecting the hemocyte parameters, especially total hemocyte count (THC). THC is mainly determined by haematopoietic mechanisms and apoptosis of hemocytes. Many studies have found that B[a]P can influence the proliferation and differentiation of hemocytes. However, the link between the toxic mechanisms of haematopoietic and environmental pollutants is not explicitly stated. This study is to investigate the toxic effects of B[a]P on haematopoietic mechanisms in C. farreri. Through the tissue expression distribution experiment and EDU assay, gill is identified as a potential haematopoietic tissue in C. farreri. Subsequently, the scallops were exposed to B[a]P (0.05, 0.5, 5 μg/L) for 1d, 3d, 6d, 10d and 15d. Then BPDE content, DNA damage, gene expression of haematopoietic factors and haematopoietic related pathways were determined in gill and hemocytes. The results showed that the expression of CDK2 was significantly decreased under B[a]P exposure through three pathways: RYR/IP3-calcium, BPDE-CHK1 and Notch pathway, resulting in cell cycle arrest. In addition, B[a]P also significantly reduced the number of proliferating hemocytes by affecting the Wnt pathway. Meanwhile, B[a]P can significantly increase the content of ROS, causing a downregulation of FOXO gene expression. The gene expression of Notch pathway and ERK pathway was also detected. The present study suggested that B[a]P disturbed differentiation by multiple pathways. Furthermore, the expression of SOX11 and CD9 were significantly decreased, which directly indicated that differentiation of hemocytes was disturbed. In addition, phagocytosis, phenoloxidase activity and THC were also significant decreased. In summary, the impairment of haematopoietic activity in C. farreri further causes immunotoxicity under B[a]P exposure. This study will improve our understanding of the immunotoxicity mechanism of bivalve under B[a]P exposure.

摘要

苯并[a]芘(B[a]P)是海洋环境中普遍存在的污染物,它有可能通过影响血细胞参数,特别是总血细胞计数(THC),来影响双壳类动物的免疫反应。THC 主要由造血机制和血细胞凋亡决定。许多研究发现,B[a]P 可以影响血细胞的增殖和分化。然而,造血和环境污染物的毒性机制之间的联系尚不清楚。本研究旨在研究 B[a]P 对皱纹盘鲍(C. farreri)造血机制的毒性作用。通过组织表达分布实验和 EDU 测定,确定了鳃是皱纹盘鲍的一个潜在造血组织。随后,将扇贝暴露于 B[a]P(0.05、0.5、5μg/L)中 1d、3d、6d、10d 和 15d。然后测定鳃和血细胞中 BPDE 含量、DNA 损伤、造血因子基因表达和造血相关途径。结果表明,B[a]P 暴露通过 RYR/IP3-钙、BPDE-CHK1 和 Notch 途径显著降低 CDK2 的表达,导致细胞周期停滞。此外,B[a]P 还通过影响 Wnt 途径显著减少增殖血细胞的数量。同时,B[a]P 可显著增加 ROS 含量,导致 FOXO 基因表达下调。还检测了 Notch 途径和 ERK 途径的基因表达。本研究表明,B[a]P 通过多种途径干扰分化。此外,SOX11 和 CD9 的表达明显下降,直接表明血细胞分化受到干扰。此外,吞噬作用、酚氧化酶活性和 THC 也显著降低。总之,B[a]P 暴露导致皱纹盘鲍造血活性受损,进一步引起免疫毒性。本研究将提高我们对双壳类动物在 B[a]P 暴露下免疫毒性机制的认识。

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