Erection induced by Tx2-6 toxin of Phoneutria nigriventer spider: expression profile of genes in the nitric oxide pathway of penile tissue of mice.
The peptides Tx2-5 and Tx2-6, isolated from the whole venom of "armed-spider"Phoneutria nigriventer venom, are directly linked with the induction of persistent and painful erection in the penis of mammals. The erection induced by Tx2-6 has been associated with the activation of nitric oxide synthases. There is a scarcity of studies focusing on the outcome of Tx2-6 at the molecular level, by this reason we evaluated the gene profile activity of this toxin at the nitric oxide (NO) pathway. After microarray analyses on cavernous tissue of mice inoculated with Tx2-6 we found that only 10.4% (10/96) of these genes were differentially expressed, showing a limited effect of the toxin on the NO pathway. We found the genes sparc, ednrb, junb, cdkn1a, bcl2, ccl5, abcc1 over-expressed and the genes sod1, s100a10 and fth1 under-expressed after inoculation of Tx2-6. The differential expressions of sparc and ednrb genes were further confirmed using real-time PCR. Interestingly, ednrb activates the L-arginine/NO/cGMP pathway that is involved in the relaxation of the cavernous body. Therefore the priapism induced by Tx2-6 is a consequence of a highly specific interference of this neurotoxin with the NO pathway.
Villanova
Fabiola E
FE
Laboratory of Medical Investigation-LIM55, University of São Paulo, São Paulo, Brazil. fvillanova@gmail.com
Andrade
Enrico
E
Leal
Elcio
E
Andrade
Priscila M
PM
Borra
Ricardo C
RC
Troncone
Lanfranco R P
LR
Magalhães
Leandro
L
Leite
Katia R M
KR
Paranhos
Mario
M
Claro
Joaquim
J
Srougi
Miguel
M
D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D020869:Gene Expression Profiling; D008297:Male; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D010410:Penile Erection / Q000187:drug effects*; D010455:Peptides / Q000494:pharmacology*; D016133:Polymerase Chain Reaction; D013111:Spider Venoms / Q000494:pharmacology*
D017931:DNA Primers; D010455:Peptides; D013111:Spider Venoms; C540367:Tx2-6 protein, Phoneutria nigriventer; D009569:Nitric Oxide