No1468 antivenom-specific binding protein (TLf2)
Ontology highlight
ABSTRACT:
ORGANISM(S): Protobothrops Flavoviridis
SUBMITTER: Tomohisa Ogawa
PROVIDER: PXD028215 | JPOST Repository | Mon Sep 06 00:00:00 GMT+01:00 2021
REPOSITORIES: jPOST
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Project description:Mucuna pruriens extract MPE pretreatment may have a direct protective effect on heart (other than immunological neutralization of the venom neurotoxin and phospholipase A2 by the anti-MPE antibodies) that renders the heart more resistant to the toxic action of the venom The direct protective effect probably involves functional changes to the cardiac tissue that enable the heart to resist the reduction of contractility and rate induced by the cobra venom.To explore the possibility of the direct action of MPE pretreatment on heart and to understand the molecular events involved in the protection of MPE pretreatment against the lethal action of Naja sputatrix venom, gene expression studies were carried out using microarray analysis. Rats were divided into four groups (n=6): negative control (abbreviated as ‘negative’ group), MPE pretreated group (abbreviated as ‘MPE’ group), N. sputatrix venom-challenge group (abbreviated as ‘NS’ group) and N. sputatrix venom-challenge to MPE pretreated animals group (abbreviated as ‘MPE-NS’ group). In the ‘MPE’ group, rats were injected with MPE at a dose of 21 mg/kg (i.p.), on day 0, 7 and 14, and sacrificed on day 21. In the ‘negative’ group (the untreated, control group), rats were injected with saline of the same volume and sacrificed also on day 21. Hearts were then harvested immediately. In the N. sputatrix venom-challenge group (‘NS’ group), untreated rats were challenged with 1.5 LD50 (1.25 ?g/g) of N. sputatrix venom whereas in the venom challenge to MPE pretreated animals group (the ‘MPE-NS’ group), MPE pretreated rats were challenged with 1.5 LD50 (1.25 ?g/g) of N. sputatrix venom, both on day 21. For the ‘NS’ and ‘MPE-NS’ group, the rats were observed for 24 h after venom challenged and hearts were harvested as soon as death occurred or 24 h after the venom injection, whichever occurred first.
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Project description:Background The generalist dipteran pupal parasitoid Nasonia vitripennis injects 79 venom peptides into the host before egg laying. This venom induces several important changes in the host, including developmental arrest, immunosuppression, and alterations to normal metabolism. It is hoped that diverse and potent bioactivities of N. vitripennis venom provide an opportunity for the design of novel acting drugs. However, currently very little is known about the individual functions of N. vitripennis venom peptides and less than half can be bioinformatically annotated. The paucity of annotation information complicates the design of studies that seek to better understand the potential mechanisms underlying the envenomation response. Although the RNA interference system of N. vitripennis provides an opportunity to functionally characterise venom encoding genes, with 79 candidates this represents a daunting task. For this reason we were interested in determining the expression levels of venom encoding genes in the venom gland, such that this information could be used to rank candidate venoms. To do this we carried out deep sequencing of the transcriptome of the venom gland and neighbouring ovary tissue and used RNA-seq to measure expression from the 79 venom encoding genes. The generation of a specific venom gland transcriptome dataset also provides further opportunities to investigate novel features of this highly specialised organ. Results High throughput sequencing and RNA-seq revealed that the highest expressed venom encoding gene in the venom gland was a serine protease called Nasvi2EG007167, which has previously been implicated in the apoptotic activity of N. vitripennis venom. As expected the RNA-seq confirmed that the N. vitripennis venom encoding genes are almost exclusively expressed in the venom gland relative to the neighbouring ovary tissue. Novel peptides appear to perform key roles in N. vitripennis venom function as only four of the highest 15 expressed venom encoding genes are bioinformatically annotationed. The high throughput sequencing data also provided evidence for the existence of an additional 471 novel genes in the Nasonia genome that are expressed in the venom gland and ovary. Finally, metagenomic analysis of venom gland transcripts identified viral transcripts that may play an important part in the N. vitripennis venom function. Conclusions The expression level information provided here for the 79 venom encoding genes provides an unbiased dataset that can be used by the N. vitripennis community to identify high value candidates for further functional characterisation. These candidates represent bioactive peptides that have value in drug development pipelines.
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