CAS Key Laboratory of Tropical Marine Bio-resources and Ecology (LMB), South China Sea Institute of Oceanology, Chinese Academy of Sciences (CAS), Guangzhou, China.
University of Chinese Academy of Sciences, Beijing, China.
Front Immunol. 2022 Jul 14;13:927880. doi: 10.3389/fimmu.2022.927880. eCollection 2022.
Heavy-metal pollution has increasingly jeopardized the habitats of marine organisms including the sea cucumber, a seafloor scavenger vital to seawater bio-decontamination, ocean de-acidification and coral-reef protection. Normal physiology including immune functions of sea cucumbers is toxicologically modulated by marine metal pollutants such as cadmium (Cd). The processes underpinning Cd's toxic effects on immune systems in the sea cucumber, , are still poorly understood. To this end, we cloned and characterized a full-length caspase-9 () cDNA in the sea cucumber, . mRNA levels evolved dynamically during embryonic development. Coelomocytes, a type of phagocytic immune effectors central to immunity, were found to express mRNA most abundantly. Hl-CASP9 protein structurally resembles caspases-2 and -9 in both invertebrate and vertebrate species, comprising a CARD domain and a CASc domain. Remarkably, was transcriptionally sensitive to abiotic oxidative stress inducers including hydrogen peroxide (HO), nitric oxide (NO) and cadmium (Cd), but insensitive to immunostimulants including lipopolysaccharide (LPS), and poly(I:C). Overexpression of augmented mitochondria-dependent apoptosis in HEK293T cells, while knock-down of blunted Cd-induced coelomocyte apoptosis . Overall, we illustrate that an evolutionarily ancient caspase-9-dependent pathway exists to sensitize coelomocytes to premature cell death precipitated by heavy metal pollutants, with important implications for negative modulation of organismal immune response in marine invertebrates.
重金属污染日益威胁到海洋生物的栖息地，包括海参，这是一种对海水生物净化、海洋去酸化和珊瑚礁保护至关重要的海底清道夫。海洋金属污染物如镉（Cd）会在毒理学上调节海参的正常生理功能，包括免疫功能。海参中 Cd 对免疫系统的毒性作用的潜在机制仍知之甚少。为此，我们克隆并鉴定了海参全长 caspase-9（）cDNA。在胚胎发育过程中，mRNA 水平呈现动态变化。腔细胞，一种对免疫至关重要的吞噬免疫效应细胞，被发现最丰富地表达 mRNA。Hl-CASP9 蛋白在结构上与无脊椎动物和脊椎动物中的 caspase-2 和 caspase-9 相似，包含一个 CARD 结构域和一个 CASc 结构域。值得注意的是，对包括过氧化氢（HO）、一氧化氮（NO）和镉（Cd）在内的非生物氧化应激诱导剂具有转录敏感性，但对包括脂多糖（LPS）和聚（I:C）在内的免疫刺激剂不敏感。过表达 caspase-9 增强了 HEK293T 细胞中线粒体依赖性细胞凋亡，而敲低 caspase-9 则减弱了 Cd 诱导的腔细胞凋亡。总之，我们表明，一种古老的 caspase-9 依赖性途径存在，使腔细胞对重金属污染物引发的过早细胞死亡敏感，这对海洋无脊椎动物的机体免疫反应的负调控具有重要意义。
