Testosterone induces apoptosis in cardiomyocytes by increasing proapoptotic signaling involving tumor necrosis factor- and renin angiotensin system
Testosterone induces apoptosis in cardiomyocytes by increasing proapoptotic signaling involving tumor necrosis factor- and renin angiotensin system
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DOI：
10.1177/0960327115571766
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发表时间：
2015-11-01
影响因子：
2.8
通讯作者：
de Andrade, T. U.
中科院分区：
文献类型：
--
作者：
do Nascimento, A. M.;de Lima, E. M.;de Andrade, T. U.
合成代谢雄激素类固醇导致心脏并发症，并已被证明在心脏细胞中表现出促凋亡作用;然而，这些作用中涉及的机制尚不清楚。本研究的目的是评估高浓度睾酮诱导的心肌细胞（H9 c2）凋亡和caspase-3（Casp-3）激活是否涉及肿瘤坏死因子（TNF-α）浓度和血管紧张素转换酶（ACE）活性的增加。用睾酮（5 × 10 - 6 mol/L）、多柔比星（9.2 × 10 - 6 mol/L）、睾酮+依那西普（Eta; 6.67 × 10 - 5 mol/L）、睾酮+氯沙坦（Los; 10 - 7 mol/L）和睾酮+ AC-DEVD-CHO（10 - 5 mol/L; Casp-3抑制剂）处理心肌细胞。通过流式细胞术和Casp-3的蛋白水解活性测定细胞凋亡。我们证明，用睾酮孵育H9 c2细胞48小时导致60-70%的细胞凋亡，用Eta、Los或AC-DEVD-CHO共处理降低了这种作用。替吉奥还诱导细胞凋亡（浓度依赖性）并增加Casp-3的蛋白水解活性，其通过共处理而降低。TNF-α和ACE活性升高睾酮治疗，而共同治疗与洛杉矶和埃塔减少这些影响。我们的结论是，睾酮，血管紧张素II，TNF-α诱导的细胞凋亡和Casp-3活性在培养的心肌细胞，这有助于降低这些细胞的活力诱导睾酮在毒性浓度之间的相互作用。
Anabolic androgenic steroids lead to cardiac complications and have been shown to exhibit proapoptotic effects in cardiac cells; however, the mechanism involved in those effects is unclear. The aim of this study was to assess whether apoptosis and the activation of caspase-3 (Casp-3) induced by testosterone in high concentrations involves increments in tumor necrosis factor- (TNF-) concentrations and angiotensin-converting enzyme (ACE) activity in cardiomyocytes (H9c2) cell cultures. Cardiomyocytes were treated with testosterone (5 x 10(-6) mol/L), doxorubicin (9.2 x 10(-6) mol/L), testosterone + etanercept (Eta; 6.67 x 10(-5) mol/L), testosterone + losartan (Los; 10(-7) mol/L), and testosterone + AC-DEVD-CHO (10(-5) mol/L; Casp-3 inhibitor). Apoptosis was determined by flow cytometry and by the proteolytic activity of Casp-3. We demonstrated that incubation of H9c2 cells for 48 h with testosterone causes the apoptotic death of 60-70% of the cells and co-treatments with Eta, Los, or AC-DEVD-CHO reduced this effect. Testosterone also induces apoptosis (concentration dependent) and increases the proteolytic activity of Casp-3, which were reduced by co-treatments. TNF- and ACE activities were elevated by testosterone treatment, while co-treatment with Los and Eta reduced these effects. We concluded that an interaction between testosterone, angiotensin II, and TNF- induced apoptosis and Casp-3 activity in cultured cardiomyocytes, which contributed to the reduced viability of these cells induced by testosterone in toxic concentrations.