Polyamine catabolism in relation to trypsin activation and apoptosis in experimental acute pancreatitis.

Abstract

BACKGROUND:

Overinduced polyamine catabolism (PC) in a transgenic rat model has been suggested to be a mediator of trypsin activation which is important in acinar cell necrosis. PC has also been observed in experimental taurodeoxycholate pancreatitis. We hypothesized that PC may be a mediator of trypsin activation in taurodeoxycholate pancreatitis.

METHODS:

Pancreatitis was induced in wild-type rats by 2 or 6% taurodeoxycholate infusion or in transgenic rats by overexpressing spermidine/spermine N(1)-acetyltransferase (SSAT). The time courses of necrosis, caspase-3 immunostaining, SSAT, polyamine levels, and trypsinogen activation peptide (TAP) were monitored. The effect of the polyamine analogue bismethylspermine (Me(2)Spm) was investigated.

RESULTS:

In a transgenic pancreatitis model, TAP and acinar necrosis increased simultaneously after the activation of SSAT, depletion of spermidine, and development of apoptosis. In taurodeoxycholate pancreatitis, necrosis developed along with the accumulation of TAP. SSAT was activated simultaneously or after TAP accumulation and less than in the transgenic model, with less depletion of spermidine than in the transgenic model. Supplementation with Me(2)Spm ameliorated the extent of acinar necrosis at 24 h, but contrary to previous findings in the transgenic model, in the taurodeoxycholate model it did not affect trypsin activation. Compared with the transgenic model, no extensive apoptosis was found in taurodeoxycholate pancreatitis.

CONCLUSIONS:

Contrary to transgenic SSAT-overinduced pancreatitis, PC may not be a mediator of trypsin activation in taurodeoxycholate pancreatitis. The beneficial effect of polyamine supplementation on necrosis in taurodeoxycholate pancreatitis may rather be mediated by other mechanisms than amelioration of trypsin activation. and IAP.

• Authors: Hai-Tao Jin, Teemu Lämsä, Panu H Nordback, Mervi T Hyvönen, Sari Räty, Isto Nordback, Karl-Heinz Herzig, Leena Alhonen, Juhani Sand
• Journal: Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.] (Pancreatology) Vol. 11 Issue 2 Pg. 83-91 ( 2011) ISSN: 1424-3911 [Electronic] Switzerland
• PMID: 21525776 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 S. Karger AG, Basel.

Chemical References

• Oligopeptides
• Polyamines
• trypsinogen activation peptide
• Spermine
• Taurodeoxycholic Acid
• Trypsinogen
• Acetyltransferases
• diamine N-acetyltransferase
• Trypsin

Topics

• Acetyltransferases (metabolism)
• Animals
• Apoptosis
• Disease Models, Animal
• Enzyme Activation
• Male
• Oligopeptides (metabolism)
• Pancreatitis (chemically induced, drug therapy, metabolism)
• Polyamines (metabolism)
• Rats
• Rats, Sprague-Dawley
• Rats, Transgenic
• Rats, Wistar
• Spermine (analogs & derivatives, therapeutic use)
• Taurodeoxycholic Acid
• Trypsin (metabolism)
• Trypsinogen (metabolism)