TXNIP regulates mitophagy in retinal Müller cells under high-glucose conditions: implications for diabetic retinopathy.

Abstract:

:Thioredoxin-interacting protein (TXNIP) is involved in oxidative stress and apoptosis in diabetic retinopathy. However, the role of TXNIP in the removal of damaged mitochondria (MT) via mitophagy, a process of macroautophagy, remains unexplored. Here we investigate the associated cellular and molecular mechanisms underlying mitophagy in retinal cells under diabetic conditions. For this, we maintained a rat Müller cell line (rMC1) under high-glucose (25 mM, HG) or low-glucose (5.5 mM, LG) condition for 5 days. Our data reveal that HG upregulates TXNIP in the cytosol as well as in the MT. Moreover, mitochondrial oxidative stress and membrane depolarization occur under prolonged hyperglycemia leading to fragmentation. These damaged MT are targeted to lysosome for mitophagic degradation, as is evident by co-localization of mitochondrial protein COXIV, a subunit of cytochrome c oxidase, with autophagosome marker LC3BII and the lysosomal membrane protein LAMP2A. In addition, under HG conditions, there is an accumulation of dynamin-related fission protein Drp1 and E3 ubiquitin ligase Parkin in damaged MT, suggesting their roles in mitochondrial fragmentation and ubiquitination, respectively, which is absent in LG conditions. Subsequently, ubiquitin receptors, optineurin and p62/sequestrome 1, bind to the damaged MT and target them to LC3BII autophagosomes. Conversely, TXNIP knockout via CRISPR/Cas9 and TXNIP gRNA prevents the HG-induced mitochondrial damage and mitophagy in rMC1. Last, TXNIP level is also significantly upregulated in the diabetic rat retina in vivo and induces radial glial fibrillary acidic protein expression, a marker for Müller glia activation, and the formation of LC3BII puncta, which are prevented by intravitreal injection of TXNIP siRNA. Therefore, TXNIP represents a potential target for preventing ocular complications of diabetes.

journal_name

Cell Death Dis

journal_title

Cell death & disease

authors

Devi TS,Somayajulu M,Kowluru RA,Singh LP

doi

10.1038/cddis.2017.190

subject

Has Abstract

pub_date

2017-05-11 00:00:00

pages

e2777

issue

5

issn

2041-4889

pii

cddis2017190

journal_volume

8

pub_type

杂志文章
  • MicroRNA-587 antagonizes 5-FU-induced apoptosis and confers drug resistance by regulating PPP2R1B expression in colorectal cancer.

    abstract::Drug resistance is one of the major hurdles for cancer treatment. However, the underlying mechanisms are still largely unknown and therapeutic options remain limited. In this study, we show that microRNA (miR)-587 confers resistance to 5-fluorouracil (5-FU)-induced apoptosis in vitro and reduces the potency of 5-FU in...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2015.200

    authors: Zhang Y,Talmon G,Wang J

    更新日期:2015-08-06 00:00:00

  • Transcription factor Six2 mediates the protection of GDNF on 6-OHDA lesioned dopaminergic neurons by regulating Smurf1 expression.

    abstract::Glial cell line-derived neurotrophic factor (GDNF) has strong neuroprotective and neurorestorative effects on dopaminergic (DA) neurons in the substantia nigra (SN); however, the underlying molecular mechanisms remain to be fully elucidated. In this study, we found that the expression level of transcription factor Six...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2016.120

    authors: Gao J,Kang XY,Sun S,Li L,Zhang BL,Li YQ,Gao DS

    更新日期:2016-05-05 00:00:00

  • Human umbilical cord mesenchymal stem cell-derived extracellular vesicles promote lung adenocarcinoma growth by transferring miR-410.

    abstract::Although accumulating evidence has linked mesenchymal stem cells (MSCs) with tumor growth, the underlying mechanisms are poorly understood. Here, we demonstrated for the first time that human umbilical cord MSCs (hUCMSCs) dramatically increased the growth of lung adenocarcinoma (LUAD) cancer cells in a xenograft tumor...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-018-0323-5

    authors: Dong L,Pu Y,Zhang L,Qi Q,Xu L,Li W,Wei C,Wang X,Zhou S,Zhu J,Wang X,Liu F,Chen X,Su C

    更新日期:2018-02-13 00:00:00

  • DDX5-targeting fully human monoclonal autoantibody inhibits proliferation and promotes differentiation of acute promyelocytic leukemia cells by increasing ROS production.

    abstract::Acute promyelocytic leukemia (APL) therapy involves the compounds cytotoxic to both malignant tumor and normal cells. Relapsed APL is resistant to subsequent chemotherapy. Novel agents are in need to kill APL cells selectively with minimal toxicity. DDX5 has been recognized to be a novel target to suppress acute myelo...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-020-02759-5

    authors: Wu J,You YQ,Ma YX,Kang YH,Wu T,Wu XJ,Hu XX,Meng QH,Huang Y,Zhang N,Pan XB

    更新日期:2020-07-20 00:00:00

  • Inhibition of Hedgehog-dependent tumors and cancer stem cells by a newly identified naturally occurring chemotype.

    abstract::Hedgehog (Hh) inhibitors have emerged as valid tools in the treatment of a wide range of cancers. Indeed, aberrant activation of the Hh pathway occurring either by ligand-dependent or -independent mechanisms is a key driver in tumorigenesis. The smoothened (Smo) receptor is one of the main upstream transducers of the ...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2016.195

    authors: Infante P,Alfonsi R,Ingallina C,Quaglio D,Ghirga F,D'Acquarica I,Bernardi F,Di Magno L,Canettieri G,Screpanti I,Gulino A,Botta B,Mori M,Di Marcotullio L

    更新日期:2016-09-22 00:00:00

  • Long noncoding RNA NEAT1, regulated by LIN28B, promotes cell proliferation and migration through sponging miR-506 in high-grade serous ovarian cancer.

    abstract::The aberrant expression of long noncoding RNAs (lncRNAs) has been reported frequently in specific cancers, including high-grade serous ovarian cancer (HGSOC). The purpose of the present study was to explore the clinical significance and underlying mechanisms of a significantly dysregulated lncRNA (NEAT1) in HGSOC. Our...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-018-0908-z

    authors: Yong W,Yu D,Jun Z,Yachen D,Weiwei W,Midie X,Xingzhu J,Xiaohua W

    更新日期:2018-08-28 00:00:00

  • Inhibition of p85, the non-catalytic subunit of phosphatidylinositol 3-kinase, exerts potent antitumor activity in human breast cancer cells.

    abstract::The phosphoinositide 3-kinases (PI3Ks) are heterodimers consisting of the catalytic subunit p110 and the regulatory subunit p85. The PI3K/Akt pathway is strongly deregulated in breast cancer (BC) representing one of the mechanisms of resistance to therapies. Therefore, the identification of inhibitors of PI3K componen...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2012.179

    authors: Folgiero V,Di Carlo SE,Bon G,Spugnini EP,Di Benedetto A,Germoni S,Pia Gentileschi M,Accardo A,Milella M,Morelli G,Bossi G,Mottolese M,Falcioni R

    更新日期:2012-12-06 00:00:00

  • Eicosapentaenoic acid attenuates dexamethasome-induced apoptosis by inducing adaptive autophagy via GPR120 in murine bone marrow-derived mesenchymal stem cells.

    abstract::Long-term use of glucocorticoids is a widespread clinical problem, which currently has no effective solution other than discontinuing the use. Eicosapentaenoic acid (EPA), an omega-3 long chain polyunsaturated fatty acid (n-3 PUFA), which is largely contained in fish or fish oil, has been reported to promote cell viab...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2016.144

    authors: Gao B,Han YH,Wang L,Lin YJ,Sun Z,Lu WG,Hu YQ,Li JQ,Lin XS,Liu BH,Jie Q,Yang L,Luo ZJ

    更新日期:2016-05-26 00:00:00

  • Plumbagin inhibits the proliferation and survival of esophageal cancer cells by blocking STAT3-PLK1-AKT signaling.

    abstract::Esophageal squamous cell carcinoma (ESCC) is one of the deadliest cancers, and it requires novel treatment approaches and effective drugs. In the present study, we found that treatment with plumbagin, a natural compound, reduced proliferation and survival of the KYSE150 and KYSE450 ESCC cell lines in a dose-dependent ...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-017-0068-6

    authors: Cao YY,Yu J,Liu TT,Yang KX,Yang LY,Chen Q,Shi F,Hao JJ,Cai Y,Wang MR,Lu WH,Zhang Y

    更新日期:2018-01-16 00:00:00

  • Comp34 displays potent preclinical antitumor efficacy in triple-negative breast cancer via inhibition of NUDT3-AS4, a novel oncogenic long noncoding RNA.

    abstract::The abnormal PI3K/AKT/mTOR pathway is one of the most common genomic abnormalities in breast cancers including triple-negative breast cancer (TNBC), and pharmacologic inhibition of these aberrations has shown activity in TNBC patients. Here, we designed and identified a small-molecule Comp34 that suppresses both AKT a...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-020-03235-w

    authors: Hao Q,Wang P,Dutta P,Chung S,Li Q,Wang K,Li J,Cao W,Deng W,Geng Q,Schrode K,Shaheen M,Wu K,Zhu D,Chen QH,Chen G,Elshimali Y,Vadgama J,Wu Y

    更新日期:2020-12-11 00:00:00

  • cBid, Bax and Bcl-xL exhibit opposite membrane remodeling activities.

    abstract::The proteins of the Bcl-2 family have a crucial role in mitochondrial outer membrane permeabilization during apoptosis and in the regulation of mitochondrial dynamics. Current models consider that Bax forms toroidal pores at mitochondria that are responsible for the release of cytochrome c, whereas Bcl-xL inhibits por...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2016.34

    authors: Bleicken S,Hofhaus G,Ugarte-Uribe B,Schröder R,García-Sáez AJ

    更新日期:2016-02-25 00:00:00

  • HMGB1 released from intestinal epithelia damaged by cholera toxin adjuvant contributes to activation of mucosal dendritic cells and induction of intestinal cytotoxic T lymphocytes and IgA.

    abstract::Cholera toxin (CT) is a potent mucosal adjuvant and oral administration of ovalbumin (OVA) antigens plus CT induces OVA-specific CD8+ cytotoxic T lymphocytes (CTLs) and IgA production in intestinal mucosa. However, the mechanisms of induction of these immune responses remain unknown. Intestinal OVA-specific CD8+ CTLs ...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-018-0665-z

    authors: Wakabayashi A,Shimizu M,Shinya E,Takahashi H

    更新日期:2018-05-24 00:00:00

  • PI3K/mTOR pathway inhibitors sensitize chronic myeloid leukemia stem cells to nilotinib and restore the response of progenitors to nilotinib in the presence of stem cell factor.

    abstract::Nilotinib is a second-generation tyrosine kinase inhibitor, designed to specifically inhibit break-point cluster region (BCR)-Abelson (ABL) and developed to treat chronic myeloid leukemia (CML) in patients showing a resistance to imatinib. We previously demonstrated that nilotinib-induced apoptosis was reduced by stem...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2013.309

    authors: Airiau K,Mahon FX,Josselin M,Jeanneteau M,Belloc F

    更新日期:2013-10-03 00:00:00

  • Myeloid lineage skewing due to exacerbated NF-κB signaling facilitates osteopenia in Scurfy mice.

    abstract::Immune surveillance through Foxp3+ regulatory T cells plays a crucial role in bone homeostasis. Scurfy, the mouse model of autoimmune IPEX syndrome, bears a loss-of-function mutation in Foxp3 that leads to multi-organ inflammation. Herein, we report that scurfy mice exhibit severe bone loss mediated by accelerated ost...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2015.87

    authors: Chen TH,Swarnkar G,Mbalaviele G,Abu-Amer Y

    更新日期:2015-04-16 00:00:00

  • Hfm1 participates in Golgi-associated spindle assembly and division in mouse oocyte meiosis.

    abstract::HFM1 (helicase for meiosis 1) is widely recognized as an ATP-dependent DNA helicase and is expressed mainly in germ-line cells. HFM1 is a candidate gene of premature ovarian failure (POF), hence it is also known as POF9. However, the roles of HFM1 in mammalian oocytes remain uncertain. To investigate the functions of ...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-020-2697-4

    authors: Wang H,Zhong C,Yang R,Yin Y,Tan R,Gao L,Gao C,Cui Y,Pu D,Wu J

    更新日期:2020-06-30 00:00:00

  • Structural insight into an evolutionarily ancient programmed cell death regulator - the crystal structure of marine sponge BHP2 bound to LB-Bak-2.

    abstract::Sponges of the porifera family harbor some of the evolutionary most ancient orthologs of the B-cell lymphoma-2 (Bcl-2) family, a protein family critical to regulation of apoptosis. The genome of the sponge Geodia cydonium contains the putative pro-survival Bcl-2 homolog BHP2, which protects sponge tissue as well as ma...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2016.469

    authors: Caria S,Hinds MG,Kvansakul M

    更新日期:2017-01-12 00:00:00

  • STIM1 promotes angiogenesis by reducing exosomal miR-145 in breast cancer MDA-MB-231 cells.

    abstract::Cancer cells secrete abundant exosomes, and the secretion can be promoted by an increase of intracellular Ca2+. Stromal interaction molecule 1 (STIM1) plays a key role in shaping Ca2+ signals. MicroRNAs (miRNAs) have been reported to be potential therapeutic targets for many diseases, including breast cancer. Recently...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-020-03304-0

    authors: Pan S,Zhao X,Shao C,Fu B,Huang Y,Zhang N,Dou X,Zhang Z,Qiu Y,Wang R,Jin M,Kong D

    更新日期:2021-01-04 00:00:00

  • Inhibition of the MAP3 kinase Tpl2 protects rodent and human β-cells from apoptosis and dysfunction induced by cytokines and enhances anti-inflammatory actions of exendin-4.

    abstract::Proinflammatory cytokines exert cytotoxic effects on β-cells, and are involved in the pathogenesis of type I and type II diabetes and in the drastic loss of β-cells following islet transplantation. Cytokines induce apoptosis and alter the function of differentiated β-cells. Although the MAP3 kinase tumor progression l...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2015.399

    authors: Varin EM,Wojtusciszyn A,Broca C,Muller D,Ravier MA,Ceppo F,Renard E,Tanti JF,Dalle S

    更新日期:2016-01-21 00:00:00

  • Discovery of a small-molecule protein kinase Cδ-selective activator with promising application in colon cancer therapy.

    abstract::Protein kinase C (PKC) isozymes play major roles in human diseases, including cancer. Yet, the poor understanding of isozymes-specific functions and the limited availability of selective pharmacological modulators of PKC isozymes have limited the clinical translation of PKC-targeting agents. Here, we report the first ...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-017-0154-9

    authors: Bessa C,Soares J,Raimundo L,Loureiro JB,Gomes C,Reis F,Soares ML,Santos D,Dureja C,Chaudhuri SR,Lopez-Haber C,Kazanietz MG,Gonçalves J,Simões MF,Rijo P,Saraiva L

    更新日期:2018-01-18 00:00:00

  • Combined reduction in the expression of MCL-1 and BCL-2 reduces organismal size in mice.

    abstract::The intrinsic apoptotic pathway is controlled by the BCL-2 family of proteins, which exhibit either a pro-death or pro-survival function. Gene knockout studies revealed that different pro-survival BCL-2 proteins are critical for the survival of distinct cell types, although overlapping functions amongst such proteins ...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-020-2376-5

    authors: Ke F,Lancaster GI,Grabow S,Murphy AJ,Strasser A

    更新日期:2020-03-13 00:00:00

  • Japanese encephalitis virus induces human neural stem/progenitor cell death by elevating GRP78, PHB and hnRNPC through ER stress.

    abstract::Japanese encephalitis virus (JEV), which is a causative agent of sporadic encephalitis, harbours itself inside the neural stem/progenitor cells. It is a well-known fact that JEV infects neural stem/progenitor cells and decreases their proliferation capacity. With mass spectrometry-based quantitative proteomic study, i...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2016.394

    authors: Mukherjee S,Singh N,Sengupta N,Fatima M,Seth P,Mahadevan A,Shankar SK,Bhattacharyya A,Basu A

    更新日期:2017-01-19 00:00:00

  • The bHLH transcription factor DEC1 promotes thyroid cancer aggressiveness by the interplay with NOTCH1.

    abstract::Aberrant re-activation of transcription factors occurs frequently in cancer. Recently, we found the basic helix-loop-helix transcription factors DEC1 and DEC2 significantly up-regulated in a model of highly aggressive thyroid cancer, raising the hypothesis that these factors might be part of the program driving progre...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-018-0933-y

    authors: Gallo C,Fragliasso V,Donati B,Torricelli F,Tameni A,Piana S,Ciarrocchi A

    更新日期:2018-08-29 00:00:00

  • Long non-coding RNA H19 confers 5-Fu resistance in colorectal cancer by promoting SIRT1-mediated autophagy.

    abstract::Chemotherapy failure is the major cause of recurrence and poor prognosis in colorectal cancer (CRC) patients. The role of the differentially expressed lncRNAs in 5-Fluorouracil chemoresistance has not fully explained. Here, we observed lncRNA H19 was associated with the 5-Fu resistance in CRC. Quantitative analysis in...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-018-1187-4

    authors: Wang M,Han D,Yuan Z,Hu H,Zhao Z,Yang R,Jin Y,Zou C,Chen Y,Wang G,Gao X,Wang X

    更新日期:2018-11-19 00:00:00

  • SOX12 promotes colorectal cancer cell proliferation and metastasis by regulating asparagine synthesis.

    abstract::The sex-determining region Y (SRY)-box (SOX) family has a crucial role in carcinogenesis and cancer progression. However, the role of SOX12 and the mechanism by which it is dysregulated in colorectal cancer (CRC) remain unclear. Here we analyzed SOX12 expression patterns in two independent CRC cohorts (cohort I, n = 3...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-019-1481-9

    authors: Du F,Chen J,Liu H,Cai Y,Cao T,Han W,Yi X,Qian M,Tian D,Nie Y,Wu K,Fan D,Xia L

    更新日期:2019-03-11 00:00:00

  • IL-22 ameliorates LPS-induced acute liver injury by autophagy activation through ATF4-ATG7 signaling.

    abstract::Uncontrollable inflammatory response acts as a driver of sepsis-associated liver injury (SALI). IL-22 plays an important role in regulating inflammatory responses, but its role in SALI remains unknown. The aim of the study was to assess the association of serum IL-22 with SALI in pediatric patients and to enclose the ...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-020-03176-4

    authors: Shao L,Xiong X,Zhang Y,Miao H,Ren Y,Tang X,Song J,Wang C

    更新日期:2020-11-11 00:00:00

  • Cancer-associated fibroblasts promote progression and gemcitabine resistance via the SDF-1/SATB-1 pathway in pancreatic cancer.

    abstract::Cancer-associated fibroblasts (CAFs), a dominant component of the pancreatic tumor microenvironment, are mainly considered as promotors of malignant progression, but the underlying molecular mechanism remains unclear. Here, we show that SDF-1 secreted by CAFs stimulates malignant progression and gemcitabine resistance...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-018-1104-x

    authors: Wei L,Ye H,Li G,Lu Y,Zhou Q,Zheng S,Lin Q,Liu Y,Li Z,Chen R

    更新日期:2018-10-18 00:00:00

  • O6-methylguanine DNA methyltransferase as a promising target for the treatment of temozolomide-resistant gliomas.

    abstract::Temozolomide (TMZ) is an alkylating agent currently used as first-line therapy for gliomas treatment due to its DNA-damaging effect. However, drug resistance occurs, preventing multi-cycle use of this chemotherapeutic agent. One of the major mechanisms of cancer drug resistance is enhanced activity of a DNA repair enz...

    journal_title:Cell death & disease

    pub_type: 杂志文章,评审

    doi:10.1038/cddis.2013.388

    authors: Fan CH,Liu WL,Cao H,Wen C,Chen L,Jiang G

    更新日期:2013-10-24 00:00:00

  • Beta1 integrin blockade overcomes doxorubicin resistance in human T-cell acute lymphoblastic leukemia.

    abstract::Growing evidence indicates that cell adhesion to extracellular matrix (ECM) plays an important role in cancer chemoresistance. Leukemic T cells express several adhesion receptors of the β1 integrin subfamily with which they interact with ECM. However, the role of β1 integrins in chemoresistance of T-cell acute lymphob...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-019-1593-2

    authors: Berrazouane S,Boisvert M,Salti S,Mourad W,Al-Daccak R,Barabé F,Aoudjit F

    更新日期:2019-05-01 00:00:00

  • Cryo-thermal therapy induces macrophage polarization for durable anti-tumor immunity.

    abstract::Many cancer therapies are being developed for the induction of durable anti-tumor immunity, especially for malignant tumors. The activation of antigen-presenting cells (APCs), including macrophages and dendritic cells (DCs), can bridge innate and adaptive immune responses against tumors. However, APCs have an immunosu...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-019-1459-7

    authors: He K,Jia S,Lou Y,Liu P,Xu LX

    更新日期:2019-03-04 00:00:00

  • 4-hydroxyphenylpyruvate dioxygenase promotes lung cancer growth via pentose phosphate pathway (PPP) flux mediated by LKB1-AMPK/HDAC10/G6PD axis.

    abstract::4-hydroxyphenylpyruvate dioxygenase (HPD) is an important modifier of tyrosine metabolism. However, the precise contribution of HPD to cancer metabolism and tumorigenesis remains unclear. In this study, we found that HPD was highly expressed in lung cancer and its higher expression correlated with poor prognosis in lu...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-019-1756-1

    authors: Shan C,Lu Z,Li Z,Sheng H,Fan J,Qi Q,Liu S,Zhang S

    更新日期:2019-07-08 00:00:00