Camacho-Pérez Milton Rafael, Díaz-Resendiz Karina Janice Guadalupe, Ortiz-Butrón Rocío, Covantes-Rosales Carlos Eduardo, Benitez-Trinidad Alma Betsaida, Girón-Pérez Daniel Alberto, Toledo-Ibarra Gladys Alejandra, Pavón Lenin, Girón-Pérez Manuel Iván
Programa de Maestría en Ciencias Biológico Agropecuarias, Universidad Autónoma de Nayarit, Carretera Tepic-Compostela Km. 9. Xalisco, Nayarit C.P. 63780, México.
Laboratorio de Inmunotoxicología, Secretaría de Investigación y Posgrado, Universidad Autónoma de Nayarit, Ciudad de la Cultura S/N, Centro, Tepic, Nayarit C.P. 63000, México.
J Leukoc Biol. 2024 Jun 28;116(1):77-83. doi: 10.1093/jleuko/qiae081.
The physiological and molecular responses of leukocytes are altered by organophosphate pesticides. Some reports have shown that diazinon causes immunotoxic effects; diazoxon, the oxon metabolite of diazinon, is attributed to influence the immune response by affecting the leukocyte cholinergic system. In this study, the in vitro effects of diazoxon on molecules involved in cell signaling (cAMP, IP3, DAG, JAK1, and STAT3), which play a crucial role in the activation, differentiation, and survival of leukocytes, were evaluated. Data indicate that diazoxon leads to a decrease in cAMP concentration and an increase in basal IP3 levels. However, diazoxon does not affect basal levels of JAK1 and STAT3 phosphorylation. Instead, diazoxon inhibits leukocyte responsiveness to phorbol myristate acetate and ionomycin, substances that, under normal conditions, enhance JAK/STAT signaling. These findings demonstrate that diazoxon significantly affects key molecular parameters related to cell signaling.
有机磷农药会改变白细胞的生理和分子反应。一些报告表明，二嗪农会产生免疫毒性作用；二嗪农的氧代代谢产物二嗪磷，被认为是通过影响白细胞胆碱能系统来影响免疫反应。在本研究中，评估了二嗪磷对细胞信号传导相关分子（cAMP、IP3、DAG、JAK1和STAT3）的体外作用，这些分子在白细胞的激活、分化和存活中起关键作用。数据表明，二嗪磷导致cAMP浓度降低和基础IP3水平升高。然而，二嗪磷不影响JAK1和STAT3磷酸化的基础水平。相反，二嗪磷抑制白细胞对佛波酯肉豆蔻酸酯和离子霉素的反应性，在正常情况下，这些物质会增强JAK/STAT信号传导。这些发现表明，二嗪磷显著影响与细胞信号传导相关的关键分子参数。
