scholarly journals Mutations of the trypsinogen activation peptide in hereditary pancreatitis

2013 ◽  
Author(s):  
Andrea Geisz
Keyword(s):  
Hereditary Pancreatitis ◽  
Trypsinogen Activation ◽  
Trypsinogen Activation Peptide ◽  
Activation Peptide

scholarly journals Mutations of the trypsinogen activation peptide in hereditary pancreatitis

Pancreatology ◽  
2013 ◽  
Vol 13 (3) ◽  
pp. S56
Author(s):  
Andrea Geisz ◽  
Peter Hegyi ◽  
Zoltan Rakonczay ◽  
László Czakó ◽  
Miklós Sahin-Tóth
Keyword(s):  
Hereditary Pancreatitis ◽  
Trypsinogen Activation ◽  
Trypsinogen Activation Peptide ◽  
Activation Peptide

The pH Modulator Chloroquine Blocks Trypsinogen Activation Peptide Generation in Cerulein-Induced Pancreatitis

Pancreas ◽  
2003 ◽  
Vol 26 (1) ◽  
pp. 15-17 ◽  
Author(s):  
Yasuji Seyama ◽  
Taiichi Otani ◽  
Akira Matsukura ◽  
Masatoshi Makuuchi
Keyword(s):  
Trypsinogen Activation ◽  
Trypsinogen Activation Peptide ◽  
Activation Peptide

Evolutionary expansion of poly-aspartate motif in the activation peptide of mouse cationic trypsinogen limits autoactivation and protects against pancreatitis

2021 ◽  
Author(s):  
Anna Orekhova ◽  
Balazs Csaba Nemeth ◽  
Zsanett Jancso ◽  
Andrea Geisz ◽  
Dora Mosztbacher ◽  
...  
Keyword(s):  
Double Mutant ◽  
Early Age ◽  
Hereditary Pancreatitis ◽  
Wild Type ◽  
Trypsinogen Activation ◽  
Histological Damage ◽  
Cationic Trypsinogen ◽  
Activation Peptide ◽  
Aspartate Residue

The activation peptide of mammalian trypsinogens typically contains a tetra-aspartate motif (positions P2-P5 in Schechter-Berger numbering) that inhibits autoactivation and facilitates activation by enteropeptidase. This evolutionary mechanism protects the pancreas from premature trypsinogen activation while allowing physiological activation in the gut lumen. Inborn mutations that disrupt the tetra-aspartate motif cause hereditary pancreatitis in humans. A subset of trypsinogen orthologs, including the mouse cationic trypsinogen (isoform T7), harbor an extended penta-aspartate motif (P2-P6) in their activation peptide. Here, we demonstrate that deletion of the extra P6 aspartate residue (D23del) increased autoactivation of T7 trypsinogen 3-fold. Mutagenesis of the P6 position in wild-type T7 trypsinogen revealed that bulky hydrophobic side-chains are preferred for maximal autoactivation and deletion-induced shift of the P7 Leu to P6 explains the autoactivation increase in the D23del mutant. Accordingly, removal of the P6 Leu by N-terminal truncation with chymotrypsin C reduced autoactivation of the D23del mutant. Homozygous T7D23del mice carrying the D23del mutation did not develop spontaneous pancreatitis and severity of cerulein-induced acute pancreatitis was comparable to that of C57BL/6N controls. However, sustained stimulation with cerulein resulted in markedly increased histological damage in T7D23del mice relative to C57BL/6N mice. Furthermore, when the T7D23del allele was crossed to a chymotrypsin-deficient background, the double-mutant mice developed spontaneous pancreatitis at an early age. Taken together, the observations argue that evolutionary expansion of the poly-aspartate motif in mouse cationic trypsinogen contributes to the natural defenses against pancreatitis and validate the role of the P6 position in autoactivation control of mammalian trypsinogens.

Urinary trypsinogen activation peptide as a marker of severe acute pancreatitis

2004 ◽  
Vol 91 (8) ◽  
pp. 1027-1033 ◽  
Author(s):  
C. D. Johnson ◽  
M. Lempinen ◽  
C. W. Imrie ◽  
P. Puolakkainen ◽  
E. Kemppainen ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
Severe Acute Pancreatitis ◽  
Trypsinogen Activation ◽  
Trypsinogen Activation Peptide ◽  
Activation Peptide

Trypsinogen activation peptide (TAP) in plasma of patients with acute pancreatitis

2000 ◽  
Vol 118 (4) ◽  
pp. A161
Author(s):  
Esko Aj Kemppainen ◽  
J.M. Mayer ◽  
Pauli A. Puolakkainen ◽  
M. Gt Raraty ◽  
J. Slavin ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
Trypsinogen Activation ◽  
Trypsinogen Activation Peptide ◽  
Activation Peptide

scholarly journals Usefulness of urinary trypsinogen-2 and trypsinogen activation peptide in acute pancreatitis: A multicenter study in Japan

2019 ◽  
Vol 25 (1) ◽  
pp. 107-117 ◽  
Author(s):  
Hiroaki Yasuda ◽  
Keisho Kataoka ◽  
Yoshifumi Takeyama ◽  
Kazunori Takeda ◽  
Tetsuhide Ito ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
Multicenter Study ◽  
Trypsinogen Activation ◽  
Trypsinogen Activation Peptide ◽  
Activation Peptide
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