NHX-5，一种内质网Na+/H+交换蛋白，与二甲双胍的作用相关。
NHX-5, an Endosomal Na+/H+ Exchanger, Is Associated with Metformin Action.
作者信息
Kim Jeongho, Lee Hye-Yeon, Ahn Jheesoo, Hyun Moonjung, Lee Inhwan, Min Kyung-Jin, You Young-Jai
机构信息
From the Department of Biological Sciences, Inha University, Incheon 22212, South Korea.
the Department of Biochemistry and Molecular Biology, Virginia Commonwealth University, Richmond, Virginia 23298, and.
出版信息
J Biol Chem. 2016 Aug 26;291(35):18591-9. doi: 10.1074/jbc.C116.744037. Epub 2016 Jul 19.
Abstract
Diabetes is one of the most impactful diseases worldwide. The most commonly prescribed anti-diabetic drug is metformin. In this study, we identified an endosomal Na(+)/H(+) exchanger (NHE) as a new potential target of metformin from an unbiased screen in Caenorhabditis elegans The same NHE homolog also exists in flies, where it too mediates the effects of metformin. Our results suggest that endosomal NHEs could be a metformin target and provide an insight into a novel mechanism of action of metformin on regulating the endocytic cycle.
摘要
糖尿病是全球最具影响力的疾病之一。最常用的抗糖尿病药物是二甲双胍。在本研究中，我们通过在秀丽隐杆线虫中进行的无偏见筛选，确定一种内体钠/氢交换体（NHE）为二甲双胍的一个新的潜在靶点。在果蝇中也存在相同的NHE同源物，它同样介导二甲双胍的作用。我们的结果表明，内体NHE可能是二甲双胍的靶点，并为二甲双胍调节内吞循环的新作用机制提供了见解。
相似文献
1
NHX-5, an Endosomal Na+/H+ Exchanger, Is Associated with Metformin Action.NHX-5，一种内质网Na+/H+交换蛋白，与二甲双胍的作用相关。
J Biol Chem. 2016 Aug 26;291(35):18591-9. doi: 10.1074/jbc.C116.744037. Epub 2016 Jul 19.
2
Calcineurin homologous proteins regulate the membrane localization and activity of sodium/proton exchangers in C. elegans.钙调神经磷酸酶同源蛋白调节秀丽隐杆线虫中钠/质子交换体的膜定位和活性。
Am J Physiol Cell Physiol. 2016 Feb 1;310(3):C233-42. doi: 10.1152/ajpcell.00291.2015. Epub 2015 Nov 11.
3
The NHX family of Na+-H+ exchangers in Caenorhabditis elegans.秀丽隐杆线虫中Na⁺-H⁺交换体的NHX家族。
J Biol Chem. 2002 Aug 9;277(32):29036-44. doi: 10.1074/jbc.M203200200. Epub 2002 May 20.
4
A reduction in intestinal cell pHi due to loss of the Caenorhabditis elegans Na+/H+ exchanger NHX-2 increases life span.由于秀丽隐杆线虫钠氢交换体NHX - 2缺失导致肠道细胞胞内pH值降低，从而延长了寿命。
J Biol Chem. 2003 Nov 7;278(45):44657-66. doi: 10.1074/jbc.M307351200. Epub 2003 Aug 25.
5
A calcineurin homologous protein is required for sodium-proton exchange events in the C. elegans intestine.钙调磷酸酶同源蛋白对于秀丽隐杆线虫肠道中的钠-质子交换事件是必需的。
Am J Physiol Cell Physiol. 2011 Dec;301(6):C1389-403. doi: 10.1152/ajpcell.00139.2011. Epub 2011 Aug 24.
6
Analysis of Ca2+ signaling motifs that regulate proton signaling through the Na+/H+ exchanger NHX-7 during a rhythmic behavior in Caenorhabditis elegans.分析 Ca2+ 信号基序如何通过线虫中的 Na+/H+ 交换器 NHX-7 调节质子信号，从而调控有节奏的行为。
J Biol Chem. 2013 Feb 22;288(8):5886-95. doi: 10.1074/jbc.M112.434852. Epub 2013 Jan 14.
7
Regulation of organelle function by metformin.二甲双胍对细胞器功能的调节。
IUBMB Life. 2017 Jul;69(7):459-469. doi: 10.1002/iub.1633. Epub 2017 Apr 26.
8
Gene knockout of NHX-3 in the soil nematode Caenorhabditis elegans leads to broad-spectrum compensatory regulation of Na/H exchangers, antiporters, and the V-type H-ATPase.在土壤线虫秀丽隐杆线虫中敲除 NHX-3 基因导致 Na+/H+ 交换器、转运体和 V 型 H+-ATP 酶的广谱补偿调节。
Comp Biochem Physiol A Mol Integr Physiol. 2023 Aug;282:111455. doi: 10.1016/j.cbpa.2023.111455. Epub 2023 May 30.
9
Interactions between endosomal maturation and autophagy: analysis of ESCRT machinery during Caenorhabditis elegans development.内体成熟与自噬之间的相互作用：秀丽隐杆线虫发育过程中内体分选转运复合体机制的分析
Methods Enzymol. 2014;534:93-118. doi: 10.1016/B978-0-12-397926-1.00006-8.
10
NRFL-1, the C. elegans NHERF orthologue, interacts with amino acid transporter 6 (AAT-6) for age-dependent maintenance of AAT-6 on the membrane.NRFL-1，秀丽隐杆线虫的 NHERF 同源物，与氨基酸转运蛋白 6（AAT-6）相互作用，以维持 AAT-6 在膜上的年龄依赖性。
PLoS One. 2012;7(8):e43050. doi: 10.1371/journal.pone.0043050. Epub 2012 Aug 15.
引用本文的文献
1
Metformin modulates the unfolded protein responses, altering lifespan and health-promoting effects in UPR-activated worms.二甲双胍调节未折叠蛋白反应，改变未折叠蛋白反应激活的线虫的寿命和促进健康的作用。
PLoS One. 2025 Jun 16;20(6):e0326100. doi: 10.1371/journal.pone.0326100. eCollection 2025.
2
Endosomal pH is an evolutionarily conserved driver of phenotypic plasticity in colorectal cancer.内体pH值是结直肠癌中表型可塑性的一个进化保守驱动因素。
NPJ Syst Biol Appl. 2024 Dec 19;10(1):149. doi: 10.1038/s41540-024-00463-0.
3
Metformin Lysosomal Targeting: A Novel Aspect to Be Investigated for Metformin Repurposing in Neurodegenerative Diseases?二甲双胍溶酶体靶向：二甲双胍在神经退行性疾病中的再利用的新研究方向？
Int J Mol Sci. 2024 Aug 15;25(16):8884. doi: 10.3390/ijms25168884.
4
An Endosomal Acid-Regulatory Feedback System Rewires Cytosolic cAMP Metabolism and Drives Tumor Progression.一种内体酸调节反馈系统重塑胞质环磷酸腺苷代谢并驱动肿瘤进展。
Mol Cancer Res. 2024 May 2;22(5):465-481. doi: 10.1158/1541-7786.MCR-23-0606.
5
A DNA nanodevice for mapping sodium at single-organelle resolution.一种用于以单细胞分辨率绘制钠分布图的 DNA 纳米器件。
Nat Biotechnol. 2024 Jul;42(7):1075-1083. doi: 10.1038/s41587-023-01950-1. Epub 2023 Sep 21.
6
Severe acute respiratory syndrome coronavirus 2 may cause liver injury Na/H exchanger.严重急性呼吸综合征冠状病毒2可能导致肝脏损伤 钠/氢交换体。
World J Virol. 2023 Jan 25;12(1):12-21. doi: 10.5501/wjv.v12.i1.12.
7
Insulin may increase disease severity and mortality of COVID-19 through Na/H exchanger in patients with type 1 and type 2 diabetes mellitus.在1型和2型糖尿病患者中，胰岛素可能通过钠/氢交换体增加COVID-19的疾病严重程度和死亡率。
J Endocrinol Invest. 2023 Apr;46(4):845-847. doi: 10.1007/s40618-022-01951-y. Epub 2022 Nov 1.
8
The Effectiveness of Antidiabetic Drugs in Treating Dementia: A Peek into Pharmacological and Pharmacokinetic Properties.抗糖尿病药物治疗痴呆的疗效：药理学和药代动力学特性初探。
Int J Mol Sci. 2022 Jun 11;23(12):6542. doi: 10.3390/ijms23126542.
9
Diabetes and coronavirus (SARS-CoV-2): Molecular mechanism of Metformin intervention and the scientific basis of drug repurposing.糖尿病与冠状病毒（SARS-CoV-2）：二甲双胍干预的分子机制与药物再利用的科学基础。
PLoS Pathog. 2021 Jun 22;17(6):e1009634. doi: 10.1371/journal.ppat.1009634. eCollection 2021 Jun.
10
Mechanisms of action of metformin in type 2 diabetes: Effects on mitochondria and leukocyte-endothelium interactions.二甲双胍在 2 型糖尿病中的作用机制：对线粒体和白细胞-内皮细胞相互作用的影响。
Redox Biol. 2020 Jul;34:101517. doi: 10.1016/j.redox.2020.101517. Epub 2020 May 25.
本文引用的文献
1
Worldwide trends in diabetes since 1980: a pooled analysis of 751 population-based studies with 4.4 million participants.1980年以来全球糖尿病趋势：对751项基于人群的研究进行的汇总分析，涉及440万参与者。
Lancet. 2016 Apr 9;387(10027):1513-1530. doi: 10.1016/S0140-6736(16)00618-8. Epub 2016 Apr 6.
2
Metformin Promotes Apoptosis but Suppresses Autophagy in Glucose-Deprived H4IIE Hepatocellular Carcinoma Cells.二甲双胍促进葡萄糖剥夺的H4IIE肝癌细胞凋亡但抑制自噬。
Diabetes Metab J. 2015 Dec;39(6):518-27. doi: 10.4093/dmj.2015.39.6.518.
3
Effects of Essential Oil from Hinoki Cypress, Chamaecyparis obtusa, on Physiology and Behavior of Flies.日本扁柏精油对果蝇生理和行为的影响
PLoS One. 2015 Dec 1;10(12):e0143450. doi: 10.1371/journal.pone.0143450. eCollection 2015.
4
Metformin: from mechanisms of action to therapies.二甲双胍：从作用机制到治疗方法。
Cell Metab. 2014 Dec 2;20(6):953-66. doi: 10.1016/j.cmet.2014.09.018. Epub 2014 Oct 30.
5
The lysosomal v-ATPase-Ragulator complex is a common activator for AMPK and mTORC1, acting as a switch between catabolism and anabolism.溶酶体 v-ATPase-Ragulator 复合物是 AMPK 和 mTORC1 的共同激活剂，作为分解代谢和合成代谢之间的开关。
Cell Metab. 2014 Sep 2;20(3):526-40. doi: 10.1016/j.cmet.2014.06.014. Epub 2014 Jul 4.
6
Metformin suppresses gluconeogenesis by inhibiting mitochondrial glycerophosphate dehydrogenase.二甲双胍通过抑制线粒体甘油磷酸脱氢酶抑制糖异生。
Nature. 2014 Jun 26;510(7506):542-6. doi: 10.1038/nature13270. Epub 2014 May 21.
7
Autophagy dysfunction and its link to Alzheimer's disease and type II diabetes mellitus.自噬功能障碍及其与阿尔茨海默病和II型糖尿病的关联。
CNS Neurol Disord Drug Targets. 2014 Mar;13(2):226-46. doi: 10.2174/18715273113126660146.
8
Christianson syndrome protein NHE6 modulates TrkB endosomal signaling required for neuronal circuit development.克里斯蒂安森综合征蛋白 NHE6 调节 TrkB 内体信号传导，对于神经元回路发育是必需的。
Neuron. 2013 Oct 2;80(1):97-112. doi: 10.1016/j.neuron.2013.07.043. Epub 2013 Sep 12.
9
Molecular mechanism of action of metformin: old or new insights?二甲双胍的作用机制：是旧观点还是新视角？
Diabetologia. 2013 Sep;56(9):1898-906. doi: 10.1007/s00125-013-2991-0. Epub 2013 Jul 9.
10
Repositioning metformin for cancer prevention and treatment.重新定位二甲双胍在癌症预防和治疗中的作用。
Trends Endocrinol Metab. 2013 Sep;24(9):469-80. doi: 10.1016/j.tem.2013.05.004. Epub 2013 Jun 15.
Zotero 插件