Unmasking venom gland transcriptomes in reptile venoms

Chen, Tianbao; Bjourson, Anthony J.; Orr, David F.; Kwok, HangFai; Rao, Pingfan; Ivanyi, Craig; Shaw, Chris

doi:10.1016/s0003-2697(02)00404-9

Cited by 38 publications

(34 citation statements)

References 24 publications

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“…With regard to the utility of using mass spectrometry for non-invasive, quantitative sampling, another pair of studies report the isolation of intact mRNA directly from venoms [204,205]. It remains to be seen how quantitative this technique will prove to be and how useful it will be for archival samples, especially those that have been repeatedly frozen and thawed, but certainly it offers exciting possibilities, especially in combination with mass spectrometry.…”

Section: Discussionmentioning

confidence: 99%

Quantitative high-throughput profiling of snake venom gland transcriptomes and proteomes (Ovophis okinavensis and Protobothrops flavoviridis)

et al. 2013

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BackgroundAdvances in DNA sequencing and proteomics have facilitated quantitative comparisons of snake venom composition. Most studies have employed one approach or the other. Here, both Illumina cDNA sequencing and LC/MS were used to compare the transcriptomes and proteomes of two pit vipers, Protobothrops flavoviridis and Ovophis okinavensis, which differ greatly in their biology.ResultsSequencing of venom gland cDNA produced 104,830 transcripts. The Protobothrops transcriptome contained transcripts for 103 venom-related proteins, while the Ovophis transcriptome contained 95. In both, transcript abundances spanned six orders of magnitude. Mass spectrometry identified peptides from 100% of transcripts that occurred at higher than contaminant (e.g. human keratin) levels, including a number of proteins never before sequenced from snakes. These transcriptomes reveal fundamentally different envenomation strategies. Adult Protobothrops venom promotes hemorrhage, hypotension, incoagulable blood, and prey digestion, consistent with mammalian predation. Ovophis venom composition is less readily interpreted, owing to insufficient pharmacological data for venom serine and metalloproteases, which comprise more than 97.3% of Ovophis transcripts, but only 38.0% of Protobothrops transcripts. Ovophis venom apparently represents a hybrid strategy optimized for frogs and small mammals.ConclusionsThis study illustrates the power of cDNA sequencing combined with MS profiling. The former quantifies transcript composition, allowing detection of novel proteins, but cannot indicate which proteins are actually secreted, as does MS. We show, for the first time, that transcript and peptide abundances are correlated. This means that MS can be used for quantitative, non-invasive venom profiling, which will be beneficial for studies of endangered species.

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Section: Discussionmentioning

confidence: 99%

Quantitative high-throughput profiling of snake venom gland transcriptomes and proteomes (Ovophis okinavensis and Protobothrops flavoviridis)

et al. 2013

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“…Cloning of the mambalgin-1 cDNA. Mambalgin-1 cDNA was cloned from the black mamba venom 31 . Lyophilized venom (Sigma) was reconstituted in lysis/ binding buffer and polyadenylated mRNAs were captured on oligo(dT25) magnetic beads (Dynal).…”

Section: Methodsmentioning

confidence: 99%

Black mamba venom peptides target acid-sensing ion channels to abolish pain

Diochot

Baron

Salinas

et al. 2012

Nature

347

227

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Polypeptide toxins have played a central part in understanding physiological and physiopathological functions of ion channels. In the field of pain, they led to important advances in basic research and even to clinical applications. Acid-sensing ion channels (ASICs) are generally considered principal players in the pain pathway, including in humans. A snake toxin activating peripheral ASICs in nociceptive neurons has been recently shown to evoke pain. Here we show that a new class of three-finger peptides from another snake, the black mamba, is able to abolish pain through inhibition of ASICs expressed either in central or peripheral neurons. These peptides, which we call mambalgins, are not toxic in mice but show a potent analgesic effect upon central and peripheral injection that can be as strong as morphine. This effect is, however, resistant to naloxone, and mambalgins cause much less tolerance than morphine and no respiratory distress. Pharmacological inhibition by mambalgins combined with the use of knockdown and knockout animals indicates that blockade of heteromeric channels made of ASIC1a and ASIC2a subunits in central neurons and of ASIC1b-containing channels in nociceptors is involved in the analgesic effect of mambalgins. These findings identify new potential therapeutic targets for pain and introduce natural peptides that block them to produce a potent analgesia.

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“…The precursor cDNAs of BBPTI-1 and unknown BBPTI-5 have been cloned from libraries derived from Burmese Daboia russelli siamensis venom according to a method developed in our laboratory [6].…”

Section: Discussionmentioning

confidence: 99%