Transnitrosylation: A Factor in Nitric Oxide-Mediated Penile Erection.
Transnitrosylation: A Factor in Nitric Oxide-Mediated Penile Erection.
复制标题
DOI：
10.1016/j.jsxm.2016.03.003
复制
发表时间：
2016-05
期刊：
影响因子：
--
通讯作者：
Burnett AL
中科院分区：
文献类型：
--
作者：
Musicki B;Lagoda G;Goetz T;La Favor JD;Burnett AL
一氧化氮（NO）信号传导不仅可通过经典的环鸟苷酸（cGMP）介导，还可通过S - 亚硝基化介导。然而，S - 亚硝基化对勃起功能以及阴茎中NO调节和氧化应激的影响仍知之甚少。
为了阐明GSNOR（S - 亚硝基化内稳态的主要调节因子）在勃起生理以及阴茎中内皮型一氧化氮合酶（eNOS）功能和氧化/亚硝化应激方面的作用。
使用成年GSNOR缺陷型和野生型（WT）小鼠。通过海绵体神经电刺激评估勃起功能。采用格里斯反应测定阴茎匀浆中的总NO。通过蛋白质免疫印迹法测定阴茎中的蛋白质S - 亚硝基化、内皮型一氧化氮合酶（eNOS）丝氨酸1177位点磷酸化（正性调节位点）、eNOS解偶联以及氧化应激标志物（4 - 羟基 - 2 - 壬烯醛[4 - HNE]、丙二醛和硝基酪氨酸）。
GSNOR缺陷型小鼠阴茎的勃起功能、eNOS功能和氧化应激
GSNOR缺陷型小鼠的勃起功能完好。与野生型小鼠阴茎相比，GSNOR - / - 小鼠阴茎中总S - 亚硝基化蛋白质增加（p < 0.05）。虽然在基线时GSNOR - / - 和野生型小鼠阴茎之间eNOS丝氨酸1177位点磷酸化无差异，但海绵体神经电刺激使野生型小鼠阴茎中的磷酸化eNOS（P - eNOS）增加（p < 0.05），而未能使GSNOR - / - 小鼠阴茎中的P - eNOS增加。与野生型小鼠相比，GSNOR缺陷型小鼠阴茎中总NO生成减少（p < 0.05），而eNOS解偶联、4 - HNE、丙二醛和硝基酪氨酸增加（p < 0.05）。
转亚硝基化机制在调节阴茎中NO生物活性方面起重要作用。GSNOR缺乏导致eNOS功能障碍和氧化损伤增加，表明阴茎中eNOS的稳态功能受转亚硝基化调控。
Nitric oxide (NO) signaling can be mediated not only through classical cGMP, but also through S-nitrosylation. The impact of S-nitrosylation on erectile function and in NO regulation and oxidative stress in the penis, however, remains poorly understood. To characterize the role of GSNOR, a major regulator of S-nitrosylation homeostasis, on erection physiology and on eNOS function and oxidative/nitrosative stress in the penis. Adult GSNOR-deficient and WT mice were used. Erectile function was assessed in response to electrical stimulation of the cavernous nerve. Total NO in penile homogenates was measured by Griess reaction. Protein S-nitrosylation, endothelial NO synthase (eNOS) phosphorylation on Ser-1177 (positive regulatory site), eNOS uncoupling, and markers of oxidative stress (4-hydroxy-2-nonenal [4-HNE], malondialdehyde, and nitrotyrosine) in the penis were measured by Western blot. Erectile function, eNOS function and oxidative stress in the penis of GSNOR-deficient mice. Erectile function was intact in GSNOR-deficient mice. Total S-nitrosylated proteins were increased (p<0.05) in the GSNOR−/− compared to WT mouse penis. While eNOS phosphorylation on Ser-1177 did not differ between the GSNOR−/− and WT mouse penis at baseline, electrical stimulation of the cavernous nerve increased (p<0.05) P-eNOS in the WT mouse penis, but failed to increase P-eNOS in the GSNOR−/− mouse penis. Total NO production was decreased (p<0.05), while eNOS uncoupling, 4-HNE, malondialdehyde, and nitrotyrosine were increased (p<0.05) in the GSNOR-deficient mouse penis compared to that of WT mice. Transnitrosylation mechanisms play an important role in regulating NO bioactivity in the penis. Deficiency of GSNOR leads to eNOS dysfunction and increased oxidative damage, suggesting that homeostatic eNOS function in the penis is governed by transnitrosylation.