Bothrops jararaca venom proteome rearrangement upon neonate to adult transition

The pharmacological activities displayed by Bothrops jararaca venom undergo a significant ontogenetic shift. Similarly, the diet of this species changes from ectothermic prey in early life to endothermic prey in adulthood. in this study we used large and representative newborn and adult venom samples consisting of pools from 694 and 110 specimens, respectively, and demonstrate a significant ontogenetic shift in the venom proteome complexity of B. jararaca. 2-DE coupled to MS protein identification showed a clear rearrangement of the toxin arsenal both in terms of the total proteome, as of the glycoproteome. N-glycosylation seems to play a key role in venom protein variability between newborn and adult specimens. Upon the snake development, the subproteome of metalloproteinases undergoes a shift from a P-III-rich to a P-I-rich profile while the serine proteinase profile does not vary significantly. We also used isobaric tag labeling (iTRAQ) of venom tryptic peptides for the first time to examine the quantitative changes in the venom toxins of B. jararaca upon neonate to adult transition. the iTRAQ analysis showed changes in various toxin classes, especially the proteinases. Our study expands the in-depth understanding of venom complexity variation particularly with regard to toxin families that have been associated with envenomation pathogenesis.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Rede de Proteoma de São PauloInst Butantan, Lab Especial Toxinol Aplicada CAT Cepid, BR-05503900 São Paulo, BrazilUniv São Paulo, Dept Bioquim, Inst Quim, BR-05508 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Ciencias Exatas & Terra, São Paulo, BrazilCtr Biotecnol UFRGS, Lab Bioquim Farmacol, Porto Alegre, RS, BrazilLNBio, Lab Nacl Biociencias, Campinas, BrazilInst Butantan, Lab Herpetol, BR-05503900 São Paulo, BrazilUniv Virginia, Dept Microbiol, Charlottesville, VA 22908 USAInst Butantan, Ctr Biotecnol, BR-05503900 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Ciencias Exatas & Terra, São Paulo, BrazilFAPESP: 07/54626-7FAPESP: 98/14307-9Rede de Proteoma de São Paulo: FAPESP 2004/14846-0/FINEP 01.07.0290.00Web of Scienc