Background
Stable polyamine homeostasis is important for cell survival and regeneration. Our
experimental studies have shown that catabolism of spermidine and spermine to putrescine
is associated with the development of pancreatitis. We investigated the pathogenetic
role of polyamine catabolism by studying the effect of a methylated polyamine analog
on taurodeoxycholate-induced acute experimental pancreatitis.
Methods
Acute pancreatitis was induced by infusion of sodium taurodeoxycholate (2%) into the
pancreatic duct. Bismethylspermine (Me2Spm) was administered as a pretreatment before the induction of pancreatitis or as
a treatment after the induction of pancreatitis. The sham operation included laparotomy
only. Pancreas tissue and blood were sampled at 24 h and 72 h after the infusion of
taurodeoxycholate and studied for pancreatitis severity (serum amylase activity, pancreatic
water content, and histology) and polyamine catabolism, which includes spermidine/spermine
N1-acetyltransferase (SSAT) activity as well as spermidine, spermine, and putrescine
concentrations in the pancreas.
Results
Sodium taurodeoxycholate-induced acute pancreatitis manifests as increases in serum
amylase and pancreatic water content, leukocytosis, and acinar cell necrosis in the
pancreas. The activity of SSAT increased significantly together with an increase in
the ratios of pancreatic putrescine/spermidine and putrescine/spermine at 24 h, which
indicates SSAT-induced polyamine catabolism. Pancreatic water content and necrosis
were reduced significantly by the treatment with Me2Spm at 24 h but not at 72 h when the polyamine homeostasis had recovered, and the
pancreatitis had progressed.
Conclusions
Taurodeoxycholate-induced acute pancreatitis was associated with activation of polyamine
catabolism in the pancreas. The polyamine analog Me2Spm ameliorated the injury in the early stage, but it did not ameliorate the late
progression of the pancreatic necrosis at 72 h. Thus, besides proteolytic enzyme activation
and the cascades of inflammation, polyamine catabolism may be an important pathogenetic
mediator of the early stages of acute pancreatitis.
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References
- Genetic approaches to the cellular functions of polyamines in mammals.Eur J Biochem. 2004; 271: 877-894
- A perspective of polyamine metabolism.Biochem J. 2003; 376: 1-14
- Activation of polyamine catabolism in transgenic rats induces acute pancreatitis.Proc Natl Acad Sci U S A. 2000; 97: 8290-8295
- Gossypol activates pancreatic polyamine catabolism in normal rats and induces acute pancreatitis in transgenic rats over-expressing spermidine/spermine N1-acetyltransferase.Scand J Gastroenterol. 2003; 38: 787-793
- Acute pancreatitis induced by activation of the polyamine catabolism in gene-modified mice and rats overexpressing spermidine/spermine N1-acetyltransferase.Scand J Gastroenterol. 2005; 40: 120-121
- Activated polyamine catabolism in acute pancreatitis: alpha-methylated polyamine analogues prevent trypsinogen activation and pancreatitis-associated mortality.Am J Pathol. 2006; 168: 115-122
- Polyamine levels in the pancreas and the blood change according to the severity of pancreatitis.Pancreatology. 2008; 8: 15-24
- Arginine induced acute pancreatitis alters the actin cytoskeleton and increases heat shock protein expression in rat pancreatic acinar cells.Gut. 2001; 49: 241-250
- Pivotal participation of nitrogen dioxide in L-arginine induced acute necrotizing pancreatitis: protective role of superoxide scavenger 4-OH-TEMPO.Biochem Biophys Res Commun. 2005; 326: 313-320
- Organ microcirculatory disturbances in experimental acute pancreatitis. A role of nitric oxide.Physiol Res. 2005; 54: 363-368
- Metabolic stability of alpha-methylated polyamine derivatives and their use as substitutes for the natural polyamines.J Biol Chem. 2005; 280: 6595-6601
- A polyamine analogue prevents acute pancreatitis and restores early liver regeneration in transgenic rats with activated polyamine catabolism.J Biol Chem. 2002; 277: 39867-39872
- Extrapancreatic multiorgan injury in a severe sublethal acute pancreatitis model.Int J Surg Investig. 1999; 1: 177-184
- A new synthesis of alpha-methylspermidine.Bioorg Khim. 2004; 30: 441-445
- Approved recommendation on IFCC methods for the measurement of catalytic concentration of enzymes. part 9. IFCC method for alpha-amylase (1,4-alpha-D-glucan 4-glucanohydrolase, EC 3.2.1.1). International federation of clinical chemistry and laboratory medicine (IFCC). Committee on enzymes.Clin Chem Lab Med. 1998; 36: 185-203
- A better model of acute pancreatitis for evaluating therapy.Ann Surg. 1992; 215: 44-56
- Preclinical antitumor efficacy of the polyamine analogue N1, N11-diethylnorspermine administered by multiple injection or continuous infusion.Clin Cancer Res. 1995; 1: 847-857
- Monitoring of the uptake and metabolism of aminooxy analogues of polyamines in cultured cells by high-performance liquid chromatography.J Chromatogr. 1992; 574: 17-21
- Mechanisms of polyamine catabolism-induced acute pancreatitis.Biochem Soc Trans. 2007; 35: 326-330
- Oxidative stress and inflammation in the pathogenesis of activated polyamine catabolism-induced acute pancreatitis.Amino Acids. 2007; 33: 323-330
- Polyamines in gut inflammation and allergy.Curr Med Chem Anti-Inflamm & Anti-Aller Agents. 2004; 3: 1-8
- Circular dichroism and NMR studies of metabolically stablealpha-methylpolyamines: spectral comparison with naturally occurring polyamines.Bioorg Chem. 2000; 28: 395-408
- Alpha-methyl polyamines: metabolically stable spermidine and spermine mimics capable of supporting growth in cells depleted of polyamines.J Med Chem. 1992; 35: 724-734
Article info
Publication history
Accepted:
March 30,
2008
Footnotes
Supported by a grant from Tampere University Hospital, A.I. Virtanen Institute for Molecular Sciences, University of Kuopio, and Engelhardt Institute of Molecular Biology, Russian Academy of Sciences.
Identification
Copyright
© 2008 Mosby, Inc. Published by Elsevier Inc. All rights reserved.
