BACKGROUND: We hypothesized that mutation of the pancreatic secretory trypsin inhibitor ( PSTI) gene may promote a predisposition to pancreatitis, possibly by reducing the inhibition of trypsin activity. Based on this hypothesis, we performed a biochemical analysis of recombinant PSTI protein. METHODS: The trypsin inhibitory activity of the recombinant protein was analyzed. The activity of PSTI protein with a point mutation of the most common type: (34)Asn (AAT)-to-Ser (AGT)(101A>G N34S: N34S) in exon 3, was compared with that of the wild type. RESULTS: The function of N34S PSTI remained unchanged under both the usual alkaline and acidic conditions compared with the wild-type PSTI. The calcium concentration did not affect the activity of recombinant PSTI. The trypsin susceptibility of the N34S protein was not increased either. CONCLUSIONS: Mechanisms other than the conformational change of PSTI associated with amino-acid substitution, such as abnormal splicing, may underlie the predisposition to pancreatitis in patients with the N34S mutation.
BACKGROUND: We hypothesized that mutation of the pancreatic secretory trypsin inhibitor ( PSTI) gene may promote a predisposition to pancreatitis, possibly by reducing the inhibition of trypsin activity. Based on this hypothesis, we performed a biochemical analysis of recombinant PSTI protein. METHODS: The trypsin inhibitory activity of the recombinant protein was analyzed. The activity of PSTI protein with a point mutation of the most common type: (34)Asn (AAT)-to-Ser (AGT)(101A>G N34S: N34S) in exon 3, was compared with that of the wild type. RESULTS: The function of N34SPSTI remained unchanged under both the usual alkaline and acidic conditions compared with the wild-type PSTI. The calcium concentration did not affect the activity of recombinant PSTI. The trypsin susceptibility of the N34S protein was not increased either. CONCLUSIONS: Mechanisms other than the conformational change of PSTI associated with amino-acid substitution, such as abnormal splicing, may underlie the predisposition to pancreatitis in patients with the N34S mutation.
Authors: Orsolya Király; Arnaud Boulling; Heiko Witt; Cédric Le Maréchal; Jian-Min Chen; Jonas Rosendahl; Cinzia Battaggia; Thomas Wartmann; Miklós Sahin-Tóth; Claude Férec Journal: Hum Mutat Date: 2007-05 Impact factor: 4.878
Authors: Viacheslav N Kalinin; Jussuf T Kaifi; Heidi Schwarzenbach; Anatoly S Sergeyev; Bjoern C Link; Dean Bogoevski; Yogesh Vashist; Jakob R Izbicki; Emre F Yekebas Journal: World J Gastroenterol Date: 2006-09-07 Impact factor: 5.742
Authors: Monique H M Derikx; Andrea Geisz; Éva Kereszturi; Miklós Sahin-Tóth Journal: Am J Physiol Gastrointest Liver Physiol Date: 2015-03-19 Impact factor: 4.052