S-Nitrosation of monocarboxylate transporter 1: inhibition of pyruvate-fueled respiration and proliferation of breast cancer cells.
S-Nitrosation of monocarboxylate transporter 1: inhibition of pyruvate-fueled respiration and proliferation of breast cancer cells.
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DOI：
10.1016/j.freeradbiomed.2014.01.031
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发表时间：
2014-04
影响因子：
7.4
通讯作者：
Hogg, Neil
中科院分区：
文献类型：
--
作者：
Diers, Anne R.;Broniowska, Katarzyna A.;Chang, Ching-Fang;Hill, R. Blake;Hogg, Neil
通过线粒体代谢的能量底物（如丙酮酸、谷氨酰胺）是增殖细胞中大分子生物合成所必需的。由于已知几种线粒体蛋白是s -亚硝化的靶标，我们确定了生物能量是否受到s -亚硝化的调节，并确定了随后对增殖的影响。使用亚硝化剂s -亚硝基- l -半胱氨酸（L-CysNO）启动细胞内s -亚硝化，可降低线粒体功能，抑制MCF7乳腺腺癌细胞的增殖。令人惊讶的是，CysNO的D异构体（D-CysNO）没有被转运到细胞中，也会导致线粒体功能障碍和增殖受限。L-和D-CysNO也抑制细胞对丙酮酸的摄取，并引起单羧酸转运体1（质子连接的丙酮酸转运体）上巯基的s -亚硝化。这些数据证明了线粒体代谢在乳腺癌增殖反应中的重要性，并强调了通过s -亚硝化抑制代谢底物摄取在细胞对亚硝化应激反应中的新作用。
Energy substrates metabolized through mitochondria (e.g., pyruvate, glutamine) are required for biosynthesis of macromolecules in proliferating cells. Since several mitochondrial proteins are known to be targets of S-nitrosation, we determined whether bioenergetics are modulated by S-nitrosation and defined the subsequent effects on proliferation. The nitrosating agent S-nitroso-L-cysteine (L-CysNO) was used to initiate intracellular S-nitrosation, and treatment decreased mitochondrial function and inhibited proliferation of MCF7 mammary adenocarcinoma cells. Surprisingly, the D isomer of CysNO (D-CysNO) which is not transported into cells also caused mitochondrial dysfunction and limited proliferation. Both L- and D-CysNO also inhibited cellular pyruvate uptake and caused S-nitrosation of thiol groups on monocarboxylate transporter 1, a proton-linked pyruvate transporter. These data demonstrate the importance of mitochondrial metabolism in proliferative responses in breast cancer and highlight a novel role for inhibition of metabolic substrate uptake through S-nitrosation of exofacial protein thiols in cellular responses to nitrosative stress.
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影响因子：
7.4
作者：
Gerencser, Akos A.;Neilson, Andy;Choi, Sung W.;Edman, Ursula;Yadava, Nagendra;Oh, Richard J.;Ferrick, David A.;Nicholls, David G.;Brand, Martin D.
通讯作者：
Brand, Martin D.
影响因子：
7.4
作者：
Dranka, Brian P.;Hill, Bradford G.;Darley-Usmar, Victor M.
通讯作者：
Darley-Usmar, Victor M.
DOI：
10.1152/ajpheart.00210.2011
发表时间：
2011-09-01
影响因子：
4.8
作者：
Diers, Anne R.;Broniowska, Katarzyna A.;Hogg, Neil
通讯作者：
Hogg, Neil
影响因子：
4.1
作者：
Dimmer, KS;Friedrich, B;Bröer, S
通讯作者：
Bröer, S
影响因子：
3.4
作者：
Hua, SM;Inesi, G
通讯作者：
Inesi, G