Role of polyamines in myocardial ischemia/reperfusion injury and their interactions with nitric oxide.

Abstract

Polyamines (putrescine, spermidine, and spermine) are present in all higher eukaryotic cells and are essential for cell growth, differentiation and apoptosis. Sharing common precursor with polyamines, nitric oxide (NO) is associated with myocardial ischemia/reperfusion injury by the generation of peroxynitrite. Although polyamines have been implicated in tissue ischemia injury, their metabolism and interactions with NO in myocardial ischemia/reperfusion injury have not been fully understood. In our experiment, when Langendorff perfused rat hearts were subjected to 40 min ischemia without reperfusion, both ornithine decarboxylase (ODC) and Spermidine/spermine N(1)-acetyltransferase (SSAT) activities were up-regulated and putrescine accumulated. While after reperfusion, ODC activity decreased and SSAT activity increased, resulting in putrescine accumulation and decreased spermidine and spermine. Meanwhile NO content was increased. In addition, sodium nitroprusside (SNP, a NO donor) decreased ODC activity in cardiac tissue homogenate but increased SSAT activity in a dose-dependent manner. Pre-treatment of isolated heart with N(omega)-nitro-L-arginine methyl ester hydrochloride (L-NAME, an inhibitor of NO synthase) increased ODC activity. Exogenous spermine (1 mM) administration prior to ischemia prevented spermine decrease, reduced cardiac myocyte necrosis and apoptosis, and promoted the recovery of cardiac function after ischemia/reperfusion. These results suggest that acute heart ischemia activates myocardial polyamine stress response characterized by increased ODC and SSAT activities and accumulation of putrescine. Ischemia/reperfusion disturbs polyamine metabolism, and the loss of spermine might be associated with NO increase and thereby influences myocardial cell viability. Exogenous spermine may protect the hearts from myocardial ischemia/reperfusion injury.

• Authors: Ya-Jun Zhao, Chang-Qing Xu, Wei-Hua Zhang, Li Zhang, Shu-Ling Bian, Qi Huang, Hong-Li Sun, Quan-Feng Li, Yan-Qiao Zhang, Yie Tian, Rui Wang, Bao-Feng Yang, Wei-Min Li
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 562 Issue 3 Pg. 236-46 (May 21 2007) ISSN: 0014-2999 [Print] Netherlands
• PMID: 17382924 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Nitric Oxide Donors
• Polyamines
• Nitroprusside
• Spermine
• Nitric Oxide
• Acetyltransferases
• diamine N-acetyltransferase
• Ornithine Decarboxylase
• Putrescine

Topics

• Acetyltransferases (metabolism)
• Animals
• Apoptosis (drug effects)
• Dose-Response Relationship, Drug
• Male
• Myocardial Reperfusion Injury (physiopathology)
• Myocytes, Cardiac (drug effects, pathology)
• Necrosis
• Nitric Oxide (metabolism)
• Nitric Oxide Donors (pharmacology)
• Nitroprusside (pharmacology)
• Ornithine Decarboxylase (metabolism)
• Polyamines (metabolism)
• Putrescine (biosynthesis)
• Rats
• Rats, Wistar
• Spermine (pharmacology)
• Up-Regulation