Experimental priapism is associated with increased oxidative stress and activation of protein degradation pathways in corporal tissue.

Experimental priapism is associated with increased oxidative stress and activation of protein degradation pathways in corporal tissue.
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DOI:
10.1038/ijir.2010.27
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发表时间:
2010-11
影响因子:
2.6
通讯作者:
Davies, K. P.
Davies, K. P.
中科院分区:
医学3区
文献类型:
--
作者:
Kanika, N. D.;Melman, A.;Davies, K. P.

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阴茎勃起障碍是一种使人衰弱的疾病,目前尚无临床接受的药物干预措施。据估计,勃起持续时间超过24小时的患者有44-90%的勃起功能障碍(ED)。在这项研究中,我们在两种勃起功能障碍的动物模型(阿片素诱导的大鼠勃起功能障碍和镰状细胞病小鼠勃起功能障碍模型)中确定是否有证据表明身体组织中氧化应激标志物增加。在这两种动物模型中,我们证明了阴茎勃起导致脂质过氧化水平升高,谷胱甘肽s -转移酶活性升高,以及身体组织中氧化损伤的蛋白质。通过Western blot分析,我们发现泛素化连接酶蛋白Nedd-4和Mdm-2以及溶酶体自噬蛋白LC3上调。抗凋亡蛋白Bcl-2也上调。总的来说,我们证明了阴茎勃起与增加的身体组织氧化应激和蛋白质降解途径的激活有关。由于氧化应激介导多种病因导致的勃起功能障碍(如糖尿病和衰老导致的勃起功能障碍)的发展,我们建议针对氧化应激的治疗可以预防由勃起功能障碍引起的勃起组织损伤。
Priapism is a debilitating disease for which there is at present no clinically accepted pharmacologic intervention. It has been estimated that priapism lasting more than 24 hours in patients is associated with a 44–90% rate of erectile dysfunction (ED). In this investigation we determined in two animal models of priapism (opiorpin-induced priapism in the rat and priapism in a mouse model of sickle cell disease) if there is evidence for an increase in markers of oxidative stress in corporal tissue. In both animal models we demonstrate that priapism results in increased levels of lipid peroxidation, glutathione S-transferase activity, and oxidatively damaged proteins in corporal tissue. Using Western blot analysis we demonstrated there is up regulation of the ubiquitination ligase proteins, Nedd-4 and Mdm-2, and the lysososomal autophage protein, LC3. The anti-apoptotic protein, Bcl-2, was also up regulated. Overall, we demonstrate that priapism is associated with increased oxidative stress in corporal tissue and the activation of protein degradation pathways. Since oxidative stress is known to mediate the development of ED resulting from several etiologies (for example ED resulting from diabetes and aging) we suggest that damage to erectile tissue resulting from priapism might be prevented by treatments targeting oxidative stress.
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