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.
Fish Shellfish Immunol. 2024 Jan;144:109278. doi: 10.1016/j.fsi.2023.109278. Epub 2023 Dec 9.
Benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide (BPDE) is the active intermediate metabolite of benzo[a]pyrene (B[a]P) and is considered the ultimate immunotoxicant. The neuroendocrine immunoregulatory network of bivalves is affected under pollutant stress. Besides, bivalves are frequently affected by pollutants in marine environments, yet the combined effects of neuroendocrine factors and detoxification metabolites on bivalves under pollutant stress and the signal pathways that mediate this immunoregulation are not well understood. Therefore, we incubated the hemocytes of Chlamys farreri with the neuroendocrine factor noradrenaline (NA) and the B[a]P detoxification metabolite BPDE, alone or in combination, to examine the immunotoxic effects of NA and BPDE on the hemocytes in C. farreri. Furthermore, the effects of NA and BPDE on the hemocyte signal transduction pathway were investigated by assessing potential downstream targets. The results revealed that NA and BPDE, alone or in combination, resulted in a significant decrease in phagocytic activity, bacteriolytic activity and the total hemocyte count. In addition, the immunotoxicity induced by BPDE was further exacerbated by co-treatment with NA, and the two showed synergistic effects. Analysis of signaling pathway factors showed that NA activated G proteins by binding to α-AR, which transmitted information to the Ca-NF-κB signaling pathway to regulate the expression of phagocytosis-associated proteins and regulated cytokinesis through the cAMP signaling pathway. BPDE could activate PTK and affect phagocytosis and cytotoxicity proteins through Ca-NF-κB signal pathway, also affect the regulation of phagocytosis and cytotoxicity by inhibiting the AC-cAMP-PKA pathway to down-regulate the expression of NF-κB and CREB. In addition, BPDE and NA may affect the immunity of hemocytes by down-regulating phagocytosis-related proteins through inhibition of the lectin pathway, while regulating the expression of cytotoxicity-related proteins through the C-type lectin. In summary, immune parameters were suppressed through Ca and cAMP dependent pathways exposed to BPDE and the immunosuppressive effects were enhanced by the neuroendocrine factor NA.
苯并[a]芘-7,8-二氢二醇-9,10-环氧化物（BPDE）是苯并[a]芘（B[a]P）的活性中间代谢物，被认为是最终的免疫毒素。双壳类动物的神经内分泌免疫调节网络在污染物胁迫下受到影响。此外，双壳类动物经常受到海洋环境中污染物的影响，但神经内分泌因子和解毒代谢物对污染物胁迫下双壳类动物的联合影响以及介导这种免疫调节的信号通路尚不清楚。因此，我们将栉孔扇贝的血细胞与神经内分泌因子去甲肾上腺素（NA）和 B[a]P 解毒代谢物 BPDE 单独或联合孵育，以研究 NA 和 BPDE 对栉孔扇贝血细胞的免疫毒性作用。此外，通过评估潜在的下游靶点，研究了 NA 和 BPDE 对血细胞信号转导途径的影响。结果表明，NA 和 BPDE 单独或联合处理均可显著降低吞噬活性、溶菌活性和总血细胞计数。此外，BPDE 与 NA 共同处理进一步加剧了 BPDE 引起的免疫毒性，两者表现出协同作用。信号通路因子分析表明，NA 通过与α-AR 结合激活 G 蛋白，将信息传递到 Ca-NF-κB 信号通路，调节吞噬相关蛋白的表达，并通过 cAMP 信号通路调节细胞分裂。BPDE 可以通过 Ca-NF-κB 信号通路激活 PTK 并影响吞噬和细胞毒性蛋白，也可以通过抑制 AC-cAMP-PKA 途径来下调 NF-κB 和 CREB 的表达，从而影响吞噬和细胞毒性的调节。此外，BPDE 和 NA 可能通过抑制凝集素途径下调吞噬相关蛋白来影响血细胞的免疫功能，同时通过 C 型凝集素调节细胞毒性相关蛋白的表达。综上所述，BPDE 通过 Ca 和 cAMP 依赖性途径抑制免疫参数，神经内分泌因子 NA 增强其免疫抑制作用。
