Impairment of gill structural integrity by manganese deficiency or excess related to induction of oxidative damage, apoptosis and dysfunction of the physical barrier as regulated by NF- k B, caspase and Nrf2 signaling in fish
Impairment of gill structural integrity by manganese deficiency or excess related to induction of oxidative damage, apoptosis and dysfunction of the physical barrier as regulated by NF- k B, caspase and Nrf2 signaling in fish
复制标题
锰缺乏或过量导致的鳃结构完整性受损，与鱼类中 NF-k B、caspase 和 Nrf2 信号传导调节的氧化损伤、细胞凋亡和物理屏障功能障碍的诱导有关
DOI：
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发表时间：
2017
影响因子：
4.7
通讯作者：
Lin Feng
中科院分区：
文献类型：
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作者：
Wei-Dan Jiang;Ren-Jun Tang;Yang Liu;Pei Wu;Sheng-Yao Kuang;Jun Jiang;Ling Tang;Wu-Neng Tang;Yong-An Zhang;Xiao-Qiu Zhou;Lin Feng
本研究首次探讨了饲料中锰对鱼类鳃结构完整性及其相关信号的可能影响。在草鱼(Ctenophyngodon Idella)饲料中添加六种不同锰水平的日粮[3.65~27.86 mg Mn/kg饲料]，饲养8周。结果表明，缺锰可加重炎症反应，表现为促炎症细胞因子(肿瘤坏死因子a、白介素8、白介素1b)表达上调，抗炎细胞因子(白介素10、转化生长因子-β1)表达下调，可能与鱼鳃组织核因子kB p65表达上调、核抑制因子kB a表达下调有关。同时，缺锰导致DNA片段化，这可能部分与鱼类鳃中的凋亡信号(caspase-3、caspase-8和caspase-9)上调有关。此外，缺锰引起的细胞凋亡可能部分与氧化损伤增加有关，表现为脂质过氧化和蛋白质氧化增加，抗氧化酶活性降低[包括锰超氧化物歧化酶、过氧化氢酶、谷胱甘肽过氧化物酶、谷胱甘肽还原酶和谷胱甘肽-S转移酶]。然而，缺锰只下调MnSOD和GST的mRNA水平，这可能与上调核因子-E2相关因子-2(Nrf2)抑制物(Keap1)有关，并且仅下调claudin-b和claudin-15的基因表达，从而扰乱鱼鳃的TJ。过量的锰会对鱼鳃的部分参数产生负面影响。根据对ROS、MDA和PC的保护作用，草鱼鳃中的最适锰水平分别为17.04、16.86和21.20 mg/kg饲料。综上所述，缺锰或过量锰可引起鱼鳃炎症、细胞凋亡、抗氧化系统紊乱和紧密连接蛋白(claudin-b和claudin-15)转录丰度的改变，这可能与鱼类鳃中的核因子-k B p65、半胱氨酸天冬氨酸氨基转移酶-(3，8，9)和Nrf2信号有关。
This study is for the first time to explore the possible effects of dietary manganese (Mn) on structural integrity and the related signaling in the gills of fish. Grass carp (Ctenopharyngodon idella) were fed with six dits containing graded levels of Mn [3.65e27.86 mg Mn/kg diet] for 8 weeks. The results firstly demonstrated that Mn deficiency aggravated inflammation indicated by up-regulation of proinflammatory cytokines (tumour necrosis factor a , interleukin 8, and interleukin 1 b mRNA levels) and down-regulation of anti-inflammatory cytokines (interleukin 10, transforming growth factor- b 1) mRNA levels, which might be partially related to the up-regulation of nuclear factor kappa B (NF- k B p65) and down-regulation of nuclear inhibitor factor k B a (i k B a ) mRNA levels in the gills of fish. Meanwhile, Mn deficiency caused DNA fragmentation, which might be partially associated with the up-regulation of the apoptosis signaling (caspase-3, caspase-8 and caspase-9) in the gills of fish. Furthermore, Mn deficiency-caused apoptosis might be partly related to the increases of oxidative damage that indicated by increases of lipid peroxidation and protein oxidation, and decreases of antioxidant enzyme activities [included Mn superoxide dismutase (MnSOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR).and glutathione-S-transferase (GST)]. However, Mn deficiency only down-regulated MnSOD and GST mRNA levels, which might be partially related to the up-regulation of NF-E2-related factor-2 (Nrf2) in-hibitor (Keap1), and only down-regulated the gene expression of claudin-b and claudin-15 to disrupt the TJ in the gills of fish. Excessive Mn led to negative effects on partial parameters studied in the gills of fish. The optimal levels of Mn based on protecting against ROS, MDA and PC in the gills of grass carp were 17.04, 16.86 and 21.20 mg/kg diet, respectively. Collectively, Mn deficiency or excess could cause inflammation, apoptosis, antioxidant system disruption and change tight junction protein (claudin-b and claudin-15) transcription abundances, which might be partially related to the NF- k B p65, caspase-(3,8,9) and Nrf2 signaling, in the gills of fish.