Protection by sulforaphane from type 1 diabetes-induced testicular apoptosis is associated with the up-regulation of Nrf2 expression and function
Protection by sulforaphane from type 1 diabetes-induced testicular apoptosis is associated with the up-regulation of Nrf2 expression and function
复制标题
萝卜硫素对 1 型糖尿病诱导的睾丸细胞凋亡的保护作用与 Nrf2 表达和功能的上调有关
DOI：
10.1016/j.taap.2014.06.009
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发表时间：
2014-09-01
影响因子：
3.8
通讯作者：
Cai, Lu
中科院分区：
文献类型：
--
作者：
Jiang, Xin;Bai, Yang;Cai, Lu
糖尿病诱导的睾丸细胞凋亡主要是由于氧化应激增加。核因子-红细胞2相关因子2（nuclear factor-erythroid 2-related factor 2，Nrf 2）是控制抗氧化系统的主要转录因子，可被萝卜硫素（sulforaphane，SFN）诱导表达。为了检测SFN是否阻止睾丸细胞凋亡，用多个低剂量链脲佐菌素诱导1型糖尿病小鼠模型。糖尿病和年龄匹配的对照小鼠每周5天每天用和不用SFN治疗3个月，然后保持6个月。糖尿病显著增加睾丸细胞凋亡，这与内质网应激和线粒体细胞死亡途径有关，表现为C/EBP同源蛋白（CHOP）、裂解的半胱天冬酶-12、Bax与Bcl 2表达比率和裂解的半胱天冬酶-3的表达增加。糖尿病还显著增加睾丸氧化损伤、炎症和纤维化，并降低生殖细胞增殖。SFN治疗前3个月可显著预防上述糖尿病效应，并可持续至治疗后3个月。SFN能够上调Nrf 2的表达和功能。后者反映了Nrf 2在Ser 40的磷酸化增加和Nrf 2下游抗氧化剂在mRNA和蛋白水平的表达。这些结果表明，1型糖尿病显著诱导睾丸细胞凋亡和损伤沿着增加的氧化应激和细胞死亡以及抑制Nrf 2表达和功能。SFN能够预防1型糖尿病小鼠睾丸的氧化损伤和凋亡，这可能与在糖尿病条件下保留睾丸Nrf 2表达和功能有关。(C)2014 Elsevier Inc. All rights reserved.
Diabetes-induced testicular apoptosis is predominantly due to increased oxidative stress. The nuclear factor-erythroid 2-related factor 2 (Nrf2), as a master transcription factor in controlling anti-oxidative systems, is able to be induced by sulforaphane (SFN). To examine whether SFN prevents testicular apoptosis, type 1 diabetic mouse model was induced with multiple low-dose streptozotocin. Diabetic and age-matched control mice were treated with and without SFN at 0.5 mg/kg daily in five days of each week for 3 months and then kept until 6 months. Diabetes significantly increased testicular apoptosis that was associated with endoplasmic reticulum stress and mitochondria] cell death pathways, shown by the increased expression of C/EBP homologous protein (CHOP), cleaved caspase-12, Bax to Bcl2 expression ratio, and cleaved caspase-3. Diabetes also significantly increased testicular oxidative damage, inflammation and fibrosis, and decreased germ cell proliferation. All these diabetic effects were significantly prevented by SFN treatment for the first 3 months, and the protective effect could be sustained at 3 months after SFN treatment. SFN was able to up-regulate Nrf2 expression and function. The latter was reflected by the increased phosphorylation of Nrf2 at Ser40 and expression of Nrf2 downstream antioxidants at mRNA and protein levels. These results suggest that type 1 diabetes significantly induced testicular apoptosis and damage along with increasing oxidative stress and cell death and suppressing Nrf2 expression and function. SFN is able to prevent testicular oxidative damage and apoptosis in type 1 diabetes mice, which may be associated with the preservation of testicular Nrf2 expression and function under diabetic condition. (C) 2014 Elsevier Inc. All rights reserved.