RESUMO
Cadmium (Cd) exposure is considered as non-infectious stressor to human and animal health. Recent studies suggest that the immunotoxicity of low dose Cd is not directly apparent, but disrupts the immune responses when infected with some bacteria or virus. But how Cd alters the adaptive immunity organ and cells remains unclear. In this study, we applied lipopolysaccharide (LPS, infectious stressor) to induced inflammation in spleen tissues and T cells, and investigated the effects after Cd exposure and the underlying mechanism. Cd exposure promoted LPS-induced the expressions of the inflammatory factors, induced abnormal initiation of autophagy, but blocked autophagic flux. The effects Cd exposure under LPS activation were reversed by the autophagy promoter Rapamycin. Under LPS activation conditions, Cd also induced oxidative stress by increasing the levels of reactive oxygen species (ROS) and malondialdehyde (MDA), and reducing total antioxidant capacity (T-AOC) activity. The increased superoxide dismutase (SOD) activity after Cd exposure might be a negative feedback or passive adaptive regulation of oxidative stress. Cd-increased autophagic flux inhibition and TNF-α expression were reversed by ROS scavenger α-tocopherol (TCP). Furthermore, under LPS activation condition, Cd promoted activation of toll-like receptor 4 (TLR4)/IκBα/NFκ-B signaling pathway and increased TLR4 protein stability, which were abolished by the pretreatment of Rapamycin. The present study confirmed that, by increasing ROS-mediated inhibiting autophagic degradation of TLR4, Cd promoted LPS-induced inflammation in spleen T cells. This study identified the mechanism of autophagy in Cd-aggravated immunotoxicity under infectious stress, which could arouse public attention to synergistic toxicity of Cd and bacterial or virus infection.
Assuntos
Autofagia , Cádmio , Inflamação , Lipopolissacarídeos , NF-kappa B , Estresse Oxidativo , Espécies Reativas de Oxigênio , Transdução de Sinais , Receptor 4 Toll-Like , Cádmio/toxicidade , Autofagia/efeitos dos fármacos , Receptor 4 Toll-Like/metabolismo , Lipopolissacarídeos/toxicidade , Espécies Reativas de Oxigênio/metabolismo , Animais , NF-kappa B/metabolismo , Transdução de Sinais/efeitos dos fármacos , Inflamação/induzido quimicamente , Estresse Oxidativo/efeitos dos fármacos , Camundongos , Baço/efeitos dos fármacos , Inibidor de NF-kappaB alfa/metabolismo , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia , MasculinoRESUMO
Phytoremediation is a widely used and cost-effective technique for in situ remediation of heavy metals. Brassica napus L. genotype with high Cd accumulation and strong Cd tolerance is an ideal candidate for phytoremediation. In this study, a hydroponic experiment was conducted to select a Brassica napus genotype with either high or low Cd accumulation from a panel of 55 genotypes. The physiological mechanisms governing Cd accumulation and Cd tolerance were then explored. BN400 and BN147 were identified as the high and low Cd accumulating genotypes, respectively. Additionally, BN400 exhibited greater tolerance to Cd stress compared to BN147. Root morphology analysis revealed that BN400 exhibited longer root length, smaller root surface area and root volume, and less root tips but bigger root diameter than BN147. Subcellular Cd distribution showed that the Cd concentrations in the cell wall and vacuole in shoot were significantly higher in BN400 than in BN147, whereas the opposite trend was observed in the roots.. Pectate/protein-integrated Cd was found to be the predominant form of Cd in both shoots and roots, with significantly higher levels in BN400 compared to BN147 in the shoot, but the opposite trend was observed in the roots. These results suggest that the long fine roots play a role in Cd accumulation. The high Cd accumulating genotype was able to retain Cd in leaf cell walls and vacuoles, and Cd was mainly present in the form of pectate/protein-integrated Cd, which contributes to its strong Cd tolerance. These findings have important implications for the screening and breeding of Brassica napus genotypes with high Cd accumulation for phytoremediation purposes.