Spermidine/spermine-N1-acetyltransferase ablation protects against liver and kidney ischemia-reperfusion injury in mice.
Spermidine/spermine-N1-acetyltransferase ablation protects against liver and kidney ischemia-reperfusion injury in mice.
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DOI：
10.1152/ajpgi.90507.2008
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发表时间：
2009-04
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影响因子：
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通讯作者：
K. Zahedi;A. Lentsch;T. Okaya;Sharon L. Barone;N. Sakai;D. Witte;L. Arend;L. Alhonen;J. Jell;J. Jänne;C. Porter;M. Soleimani
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作者：
K. Zahedi;A. Lentsch;T. Okaya;Sharon L. Barone;N. Sakai;D. Witte;L. Arend;L. Alhonen;J. Jell;J. Jänne;C. Porter;M. Soleimani
精胺/亚精胺-N1-乙酰转移酶 (SSAT) 是多胺反向转换级联的限速酶，其表达在缺血再灌注损伤 (IRI) 后增加。我们假设 SSAT 在 IRI 的中介中发挥重要作用。为了检验我们的假设，通过结扎肝或肾动脉对野生型 (SSAT-wt) 和 SSAT 缺陷 (SSAT-ko) 小鼠进行肝脏或肾脏 IRI。 IRI 后，SSAT 活性的下游副产物腐胺 (Put) 的肝脏和肾脏含量在 SSAT-wt 动物中增加，但在 SSAT-ko 动物中没有增加，表明多胺反向转换在 SSAT 缺陷小鼠中不起作用。当接受肝脏 IRI 治疗时，与 SSAT-wt 小鼠相比，SSAT-ko 小鼠显着免受肝损伤。同样，与 SSAT-wt 小鼠相比，接受肾 IRI 治疗的 SSAT-ko 动物对肾小管损伤的保护作用明显更强。这些研究表明，SSAT 缺陷的动物可以免受 IRI 的影响，并表明 SSAT 是 IRI 组织损伤的重要介质。
Expression of spermine/spermidine-N1-acetyltransferase (SSAT), the rate-limiting enzyme of polyamine backconversion cascade, increases after ischemia-reperfusion injuries (IRI). We hypothesized that SSAT plays an important role in the mediation of IRI. To test our hypothesis, wild-type (SSAT-wt) and SSAT-deficient (SSAT-ko) mice were subjected to liver or kidney IRI by ligation of hepatic or renal arteries. The liver and kidney content of putrescine (Put), a downstream by-product of SSAT activity, increased in SSAT-wt animals but not in SSAT-ko animals after IRI, indicating that polyamine backconversion is not functional in SSAT-deficient mice. When subjected to hepatic IRI, SSAT-ko mice were significantly protected against liver damage compared with SSAT-wt mice. Similarly, SSAT-ko animals subjected to renal IRI showed significantly greater protection against damage to kidney tubules than SSAT-wt mice. These studies indicate that SSAT-deficient animals are protected against IRI and suggest that SSAT is an important mediator of the tissue damage in IRI.