Geniposide inhibits glucolipotoxicity and cooperates with Txnip knockdown to potentiate cell adaption to endoplasmic reticulum stress in pancreatic beta cells

Liu Min; Liu Chunyan; Shen Shenli; Liu Jianhui; Yin Fei

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Geniposide inhibits glucolipotoxicity and cooperates with Txnip knockdown to potentiate cell adaption to endoplasmic reticulum stress in pancreatic beta cells

机译：Geniposide抑制葡糖胆毒性，并用Txnip敲低合作，以使细胞适应于胰腺β细胞中的内质网胁迫

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Abstract Thioredoxin‐interacting protein (Txnip), a negative regulator of thioredoxin, has become an attractive therapeutic target to alleviate metabolic diseases. Our previous data demonstrated that geniposide improved glucose‐stimulated insulin secretion by accelerating Txnip degradation and prevented the early‐stage apoptosis of pancreatic β cells induced by palmitate, but the underlying mechanisms are still unclear. The objective of this study is to identify the role of Txnip in geniposide preventing the apoptosis of pancreatic β cells induced by high glucose and palmitate (HG/PA). The results revealed that geniposide attenuated HG/PA‐induced cell apoptosis and the expression of Bax and caspase‐3, while increasing mitochondrial membrane potential and the anti‐apoptotic protein levels of heme‐oxygenase‐1 (HO‐1) and Bcl‐2 in INS‐1 rat pancreatic β cells. Knockdown of the Txnip gene raised the levels of anti‐apoptotic proteins HO‐1 and Bcl‐2 and geniposide potentiated the effect of Txnip when the INS‐1 cells were challenged by HG/PA. Furthermore, geniposide enhanced the adoptive unfolded protein response by increasing the phosphorylation of PERK/eIF2α and IRE1α in HG/PA‐treated INS‐1 cells. The results together suggest that geniposide might be useful to antagonize glucolipotoxicity and Txnip might be a pleiotropic cellular factor in pancreatic β cells.

机译：摘要硫氧还蛋白相互作用蛋白（Txnip）是硫氧还蛋白的负性调节因子，已成为缓解代谢性疾病的一个有吸引力的治疗靶点。我们之前的数据表明，京尼平苷通过加速Txnip降解来改善葡萄糖刺激的胰岛素分泌，并阻止棕榈酸酯诱导的胰腺β细胞早期凋亡，但其潜在机制尚不清楚。本研究的目的是确定Txnip在京尼平苷预防高糖和棕榈酸酯（HG/PA）诱导的胰腺β细胞凋亡中的作用。结果显示，京尼平甙可减弱HG/PA诱导的细胞凋亡以及Bax和caspase-3的表达，同时增加INS-1大鼠胰腺β细胞的线粒体膜电位和血红素加氧酶-1（HO-1）和Bcl-2的抗凋亡蛋白水平。敲除Txnip基因可提高抗凋亡蛋白HO-1和Bcl-2的水平，当HG/PA攻击INS-1细胞时，京尼平苷可增强Txnip的作用。此外，京尼平苷通过增加HG/PA处理的INS-1细胞中PERK/eIF2α和IRE1α的磷酸化，增强过继未折叠蛋白反应。这些结果共同表明，京尼平苷可能有助于对抗糖脂毒性，Txnip可能是胰腺β细胞中的一种多效性细胞因子。

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来源
《Cell biology international.》 |2020年第7期|共9页
作者
Liu Min; Liu Chunyan; Shen Shenli; Liu Jianhui; Yin Fei;
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作者单位

Chongqing Key Lab of Medicinal Chemistry &

Molecular PharmacologyChongqing University of;

Chongqing Key Lab of Medicinal Chemistry &

Molecular PharmacologyChongqing University of;

Chongqing Key Lab of Medicinal Chemistry &

Molecular PharmacologyChongqing University of;

Chongqing Key Lab of Medicinal Chemistry &

Molecular PharmacologyChongqing University of;

Chongqing Key Lab of Medicinal Chemistry &

Molecular PharmacologyChongqing University of;

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原文格式 PDF
正文语种 eng
中图分类细胞生物学;
关键词
Bax; Bcl‐2; cell apoptosis; geniposide; thioredoxin‐interacting protein (Txnip);

机译：Bax;Bcl-2;细胞凋亡;栀子苷;硫磷脂相互作用蛋白（TXNIP）;

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2. p28GANK inhibits endoplasmic reticulum stress-induced cell death via enhancement of the endoplasmic reticulum adaptive capacity [J] . Rong-Yang Dai, Sheng-Li Yang, Hong-Yang Wang, 细胞研究（英文版） . 2009,第011期
3. MicroRNA-24 promotes pancreatic beta cells toward dedifferentiation to avoid endoplasmic reticulum stress-induced apoptosis [J] . Yunxia Zhu, Yi Sun, Yuncai Zhou, 分子细胞生物学报：英文版 . 2019,第009期
4. MicroRNA-24 promotes pancreatic beta cells toward dedifferentiation to avoid endoplasmic reticulum stress-induced apoptosis [J] . Yunxia Zhu, Xiao Han, Yi Sun, 分子细胞生物学报（英文版） . 2019,第009期
5. Neuronal nitric oxide synthase protects the pancreatic beta cell from glucolipotoxicity-induced endoplasmic reticulum stress and apoptosis [J] . E. Bachar, Y. Ariav, E. Cerasi, Diabetologia . 2010,第10期

机译：神经元一氧化氮合酶可保护胰岛β细胞免受糖脂毒性诱导的内质网应激和凋亡
6. Interferon-γ potentiates endoplasmic reticulum stress-induced death by reducing pancreatic beta cell defence mechanisms [J] . P. Pirot, D. L. Eizirik, A. K. Cardozo Diabetologia . 2006,第6期

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7. IL-1beta caused pancreatic beta-cells apoptosis is mediated in part by endoplasmic reticulum stress via the induction of endoplasmic reticulum Ca2+ release through the c-Jun N-terminal kinase pathway. [J] . Wang Q, Zhang H, Zhao B Molecular and Cellular Biochemistry: An International Journal for Chemical Biology . 2009,第1a2期

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8. MOLECULAR CHARACTERIZATION OF ROUGH ENDOPLASMIC RETICULUM SUBPROTEOME IN PANCREATIC BETA CELLS [C] . Jin-sook Lee, Yanning Wu, Patracia Skallos, American Society for Mass Spectrometry Conference on Mass Spectrometry and Allied Topics . 2013

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12. Fatty Acid Synthase Inhibitors Engage the Cell Death Program Through the Endoplasmic Reticulum [R] . Kridel, S. J. 2008

机译：脂肪酸合成酶抑制剂通过内质网参与细胞死亡程序

Geniposide inhibits glucolipotoxicity and cooperates with Txnip knockdown to potentiate cell adaption to endoplasmic reticulum stress in pancreatic beta cells

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