Unusual cleavage of peptidic hormones generated by trypanosome enzymes released in infested rat serum.
Gonad and thyroid dysfunctions are often observed in human and experimental models during african trypanosomiasis. The enzymatic activity of components released by the trypanosomes towards peptide hormones (e.g. GnRH, TRH) have consequently been studied. The incubation products of GnRH by (i) healthy or infested rat serum: (ii) trypanosomal components released by using a specific procedure; (iii) infested and normal rat brain extracts have been analysed by RP-HPLC fractionation. The peptide cleavage has been assessed by determination of either the amino acid compositions or relative molecular weight (by FAB mass spectrometry) of the different resolved HPLC fractions. Different protease inhibitors and a reducing agent have also been tested and a serine, cation-sensitive, thiol-dependent endopeptidase activity has been predominantly identified to be released by the trypanosomes in host circulation. It has been shown that the peptidase activity(ies) is(are) able to: (i) degrade the peptide hormones (GnRH, TRH) considered as important neuromodulators and neurotransmitters; (ii) generate an unusual N-terminal tetrapeptide (GnRH1-4) appearing to be still active towards the gonadal hypothalamo-pituitary axis.
Tetaert
D
D
National Institute of Health, Lille, France.
Soudan
B
B
Huet-Duvillier
G
G
Degand
P
P
Boersma
A
A
D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D010450:Endopeptidases / Q000097:blood; D007987:Gonadotropin-Releasing Hormone / Q000737:chemistry / Q000378:metabolism; D006728:Hormones / Q000737:chemistry / Q000378:metabolism*; D008297:Male; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D010455:Peptides / Q000737:chemistry / Q000378:metabolism*; D010902:Pituitary Gland / Q000378:metabolism; D051381:Rats; D013737:Testis / Q000378:metabolism; D013973:Thyrotropin-Releasing Hormone / Q000737:chemistry / Q000378:metabolism; D014346:Trypanosoma brucei brucei / Q000201:enzymology*; D014353:Trypanosomiasis, African / Q000201:enzymology* / Q000469:parasitology
D006728:Hormones; D010446:Peptide Fragments; D010455:Peptides; D007987:Gonadotropin-Releasing Hormone; D013973:Thyrotropin-Releasing Hormone; D010450:Endopeptidases