ELAVL1a is an immunocompetent protein that protects zebrafish embryos from bacterial infection.

Previous studies have shown that ELAVL1 plays multiple roles, but its overall biological function remains ill-defined. Here we clearly demonstrated that zebrafish ELAVL1a was a lipoteichoic acid (LTA)- and LPS-binding protein abundantly stored in the eggs/embryos of zebrafish. ELAVL1a acted not only as a pattern recognition receptor, capable of identifying LTA and LPS, as well as bacteria, but also as an effector molecule, capable of inhibiting the growth of Gram-positive and -negative bacteria. Furthermore, we reveal that the C-terminal 62 residues of ELAVL1a positioned at 181-242 were indispensable for ELAVL1a antibacterial activity. Additionally, site-directed mutagenesis revealed that the hydrophobic residues Val192/Ile193, as well as the positively charged residues Arg203/Arg204, were the functional determinants contributing to the antimicrobial activity of rELAVL1a. Importantly, microinjection of rELAVL1a into embryos markedly promoted their resistance against pathogenic Aeromonas hydrophila challenge, and this pathogen-resistant activity was considerably reduced by co-injection of anti-ELAVL1a antibody or by knockdown with morpholino for elavl1a. Collectively, our results indicate that ELAVL1a is a maternal immune factor that can protect zebrafish embryos from bacterial infection. This work also provides another angle for understanding the biological roles of ELAVL1a.

Conservation of eATP perception throughout multicellular animal evolution: Identification and functional characterization of coral and amphioxus P2X7-like receptors and flounder P2X7 receptor.

Perception of extracellular ATP (eATP), a common endogenous damage-associated molecular pattern, is through its receptor P2X7R. If eATP/P2X7R signaling is conserved throughout animal evolution is unknown. Moreover, little information is currently available regarding P2X7R in invertebrates. Here we demonstrated that the coral P2X7-like receptor, AdP2X7RL, the amphioxus P2X7-like receptor, BjP2X7RL and the flounder P2X7 receptor, PoP2X7R, shared common features characteristic of mammalian P2X7R, and their 3D structures displayed high resemblance to that of human P2X7R. Expression of Adp2x7rl, Bjp2x7rl and Pop2x7r was all subjected to the regulation by LPS and ATP. We also showed that AdP2X7RL, BjP2X7RL and PoP2X7R were distributed on the plasma membrane in AdP2X7RL-, BjP2X7RL- and PoP2X7R-expressing HEK cells, and had strong affinity to eATP. Importantly, the binding of AdP2X7RL, BjP2X7RL and PoP2X7R to eATP all induced similar downstream responses, including induction of cytokines (IL-1ß, IL-6, IL-8 and CCL-2), enhancement of phagocytosis and activation of AKT/ERK-associated signaling pathway observed for mammalian P2X7R. Collectively, our results indicate for the first time that both coral and amphioxus P2X7RL as well as flounder P2X7R can interact with eATP, and induce events that trigger mammalian mechanisms, suggesting the high conservation of eATP perception throughout multicellular animal evolution.

Dietary Intake of ß-Glucans Can Prolong Lifespan and Exert an Antioxidant Action on Aged Fish Nothobranchius guentheri.

One of the widely accepted conjectures regarding mechanisms of aging is probably the oxidative stress hypothesis. ß-1,3-Glucans, well-known immunostimulants, have been shown to increase nonspecific immunity and resistance against infections or pathogenic bacteria in several fish species, but its antiaging function remains poorly understood. By feeding of ß-1,3-glucans to the annual fish, Nothobranchius guentheri, we detected the survivorship of the fish and estimated the development of age-related biomarkers at different stages. We first showed that administration of ß-1,3-glucans was able to prolong the lifespan of the fish (p < 0.05). We then showed that ß-1,3-glucans clearly reduced the accumulation of lipofuscin in the gills and the senescence-associated ß-galactosidase in the caudal fins. Moreover, ß-1,3-glucans were able to lower the levels of protein oxidation, lipid peroxidation, and reactive oxygen species (ROS) in the muscles. Finally, ß-1,3-glucans could promote the activities of the antioxidant enzymes, including catalase, superoxide dismutase, and glutathione peroxidase in the fish, and slow down the increase of P66shc, a critical factor involved in the regulation of intracellular ROS contents. These data together suggest for the first time that ß-1,3-glucans can extend the lifespan, delay the onset of age-related biomarkers and exert an antioxidant action of the aged fish, N. guentheri. It also implies that ß-1,3-glucans may be potentially useful for health care in the elderly, including extension of the lifespan.