Abstract:
:Autophagy has a fundamental role in maintaining cell homeostasis. Although autophagy has been implicated in glaucomatous pathology, how it regulates retinal ganglion cell (RGC) injury is largely unknown. In the present work, we found that biphasic autophagy in RGCs occurred in a mouse model of chronic ocular hypertension (COH), accompanied by activation of Rac1, a member of the Rho family. Rac1 conditional knockout (Rac1 cKO) in RGCs attenuated RGC apoptosis, in addition to blocking the increase in the number of autophagosomes and the expression of autophagy-related proteins (Beclin1, LC3-II/I, and p62) in COH retinas. Electron micrograph and double immunostaining of LAMP1 and LC3B showed that Rac1 cKO accelerated autolysosome fusion in RGC axons of COH mice. Inhibiting the first autophagic peak with 3-methyladenine or Atg13 siRNA reduced RGC apoptosis, whereas inhibiting the second autophagic peak with 3-MA or blocking autophagic flux by chloroquine increased RGC apoptosis. Furthermore, Rac1 cKO reduced the number of autophagosomes and apoptotic RGCs induced by rapamycin injected intravitreally, which suggests that Rac1 negatively regulates mTOR activity. Moreover, Rac1 deletion decreased Bak expression and did not interfere with the interaction of Beclin1 and Bcl-2 or Bak in COH retinas. In conclusion, autophagy promotes RGC apoptosis in the early stages of glaucoma and results in autophagic cell death in later stages. Rac1 deletion alleviates RGC damage by regulating the cross talk between autophagy and apoptosis through mTOR/Beclin1-Bak. Interfering with the Rac1/mTOR signaling pathway may provide a new strategy for treating glaucoma.
journal_name
Cell Death Disjournal_title
Cell death & diseaseauthors
Zhang ML,Zhao GL,Hou Y,Zhong SM,Xu LJ,Li F,Niu WR,Yuan F,Yang XL,Wang Z,Miao Ydoi
10.1038/s41419-020-02951-7subject
Has Abstractpub_date
2020-09-10 00:00:00pages
734issue
9issn
2041-4889pii
10.1038/s41419-020-02951-7journal_volume
11pub_type
杂志文章abstract::Epidemiological studies show obvious gender differences in the incidence and the prognosis of bladder cancer (BCa). Estrogen receptor alpha (ERα) was recently shown to play a protective role in BCa. However, the mechanisms by which ERα mediates BCa progression need to be further elucidated. In the present study, we ex...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-1827-3
更新日期:2019-08-27 00:00:00
abstract::Withanolide E, a steroidal lactone from Physalis peruviana, was found to be highly active for sensitizing renal carcinoma cells and a number of other human cancer cells to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis. Withanolide E, the most potent and least toxic of five TRAIL-se...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2015.38
更新日期:2015-02-26 00:00:00
abstract::MicroRNAs (miRNAs) have been demonstrated to affect the biological processes of cancers and showed great potential for prognostic biomarkers. In this study, we screened differentially expressed miRNAs in ccRCC based on three dimensions of metastasis, prognosis, and differential expression compared to normal tissue usi...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-03306-y
更新日期:2021-01-04 00:00:00
abstract::A major hallmark of Parkinson's disease (PD) is the degeneration of dopaminergic neurons in the substantia nigra, and the causative mechanism is thought to be the activation of programmed neuronal death. Necroptosis is a regulated process of cell death triggered by RIPK1. Although the pathophysiology of PD has been st...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-1809-5
更新日期:2019-08-05 00:00:00
abstract::Current preclinical models in tumor biology are limited in their ability to recapitulate relevant (patho-) physiological processes, including autophagy. Three-dimensional (3D) growth cultures have frequently been proposed to overcome the lack of correlation between two-dimensional (2D) monolayer cell cultures and huma...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2017.398
更新日期:2017-08-24 00:00:00
abstract::Estrogen receptor-alpha positive (ER(+)) breast cancers comprise the majority of human breast cancers, but molecular mechanisms underlying this subtype of breast cancers remain poorly understood. Here, we show that ER(+) mammary luminal tumors arising in Tip30(-/-)MMTV-Neu mice exhibited increased enrichment of lumina...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2014.224
更新日期:2014-05-22 00:00:00
abstract::Transplantation of neural progenitors derived from human embryonic stem cells (hESCs) provides a potential therapy for ischemic stroke. However, poor graft survival within the host environment has hampered the benefits and applications of cell-based therapies. The present investigation tested a preconditioning strateg...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2009.22
更新日期:2010-01-01 00:00:00
abstract::Direct pharmacological targeting of the anti-apoptotic B-cell lymphoma-2 (BCL-2) family is an attractive therapeutic strategy for treating cancer. Obatoclax is a pan-BCL-2 family inhibitor currently in clinical development. Here we show that, although obatoclax can induce mitochondrial apoptosis dependent on BCL-2 ass...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2010.86
更新日期:2010-12-16 00:00:00
abstract::Inhibition of human mitochondrial peptide deformylase (HsPDF) depolarizes the mitochondrial membrane, reduces mitochondrial protein translation and causes apoptosis in Burkitt's lymphoma. We showed that HsPDF mRNA and protein levels were overexpressed in cancer cells and primary acute myeloid leukemia samples. Myc reg...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2014.112
更新日期:2014-03-27 00:00:00
abstract::Brown adipose tissue (BAT) dissipates metabolic energy and mediates non-shivering thermogenesis, thereby boosting energy expenditure. Increasing BAT mass and activity is expected to be a promising strategy for combating obesity; however, few medications effectively and safely recruit and activate BAT in humans. Berber...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-1706-y
更新日期:2019-06-13 00:00:00
abstract::The clinical use of the antineoplastic drug cisplatin is limited by its deleterious nephrotoxic side effect. Cisplatin-induced nephrotoxicity is associated with an increase in oxidative stress, leading ultimately to renal cell death and irreversible kidney dysfunction. Oxidative stress could be modified by the cystic ...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2013.355
更新日期:2013-10-03 00:00:00
abstract::The homolog of p53 gene, p63, encodes multiple p63 protein isoforms. TAp63 proteins contain an N-terminal transactivation domain similar to that of p53 and function as tumor suppressors; whereas ΔNp63 isoforms, which lack the intact N-terminal transactivation domain, are associated with human tumorigenesis. Accumulati...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2013.468
更新日期:2013-12-05 00:00:00
abstract::Liver cancer is the second most common cause of cancer-related death worldwide. Approximately 70-90% of primary liver cancers are hepatocellular carcinoma (HCC). Currently, HCC patient prognosis is unsatisfactory due to high metastasis and/or post-surgical recurrence rates. Therefore, new therapeutic methods for inhib...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-0534-9
更新日期:2018-05-01 00:00:00
abstract::Chronic lymphocytic leukemia (CLL) can be divided into groups based on biomarkers of poor prognosis. The expression of the tyrosine kinase ZAP-70 (member of the Syk tyrosine kinase family) in CLL cells is associated with shorter overall survival in CLL patients. Currently, there is a lack of targeted therapies for pat...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2014.391
更新日期:2014-10-02 00:00:00
abstract::Bone loss in postmenopausal osteoporosis is induced chiefly by an imbalance of bone-forming osteoblasts and bone-resorbing osteoclasts. Salubrinal is a synthetic compound that inhibits de-phosphorylation of eukaryotic translation initiation factor 2 alpha (eIF2α). Phosphorylation of eIF2α alleviates endoplasmic reticu...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-2159-z
更新日期:2019-12-04 00:00:00
abstract::Phenothiazines are a family of heterocyclic compounds whose clinical utility includes treatment of psychiatric disorders as well as chemotherapy-induced emesis. Various studies have demonstrated that these compounds possess cytotoxic activities in tumor cell lines of different origin. However, there is considerable co...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2014.56
更新日期:2014-03-13 00:00:00
abstract::Providing a conducive microenvironment is critical to increase survival of transplanted stem cells in regenerative therapy. Hyperglycemia promotes stem cell death impairing cardiac regeneration in the diabetic heart. Understanding the molecular mechanisms of high glucose-induced stem cell death is important for improv...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-2367-6
更新日期:2020-03-13 00:00:00
abstract::Peroxiredoxin (Prdx) 2 is an antioxidant protein that utilizes its redox-sensitive cysteine groups to reduce hydrogen peroxide molecules and protect cells against oxidative damage from reactive oxygen species (ROS). However, its function in trophoblasts at the maternal-fetal interface has not been clarified yet. In th...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2017.301
更新日期:2017-06-29 00:00:00
abstract::Due to limited treatment options, pre-eclampsia (PE) is associated with fetal perinatal and maternal morbidity and mortality. During the causes of PE, failure of uterine spiral artery remodeling which might be related to functioning abnormally of trophoblast cells, result in the occurrence and progression of PE. Recen...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2017.503
更新日期:2017-10-12 00:00:00
abstract::Although increasing evidence indicated that deregulation of microRNAs (miRNAs) contributed to tumor initiation and progression, but little is known about the biological role of miR-340 in ovarian cancer (OC). In this study, we found that miR-340 expression was downregulated in OC tissues compared with its expression i...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-1604-3
更新日期:2019-05-08 00:00:00
abstract::Hepatocellular carcinoma (HCC) is one of the greatest life threats for Chinese people, and the prognosis of this malignancy is poor due to the strong chemotherapy resistance in patients. Notch pathway components mediate cell survival and epithelial-mesenchymal transition (EMT), and also participate in the induction of...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-0804-6
更新日期:2018-07-03 00:00:00
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
更新日期:2018-11-19 00:00:00
abstract::Our recent study identified a list of differentially expressed microRNAs (miRNAs) in human prostate cancer (PCa) tissues compared to adjacent benign prostate tissues. In the current study, to identify the crucial miRNA-mRNA regulatory biomodule involved into prostate carcinogenesis based on the previous miRNA expressi...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-0293-7
更新日期:2018-02-21 00:00:00
abstract::Little is known about the function of Keratin 80 (KRT80), an epithelial keratin, in cancer. This study investigated the role of KRT80 in the prognosis of colorectal carcinoma (CRC) and the underlying mechanisms involved in CRC migration and invasion. We analyzed the expression of KRT80 using The Cancer Genome Atlas an...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-1030-y
更新日期:2018-09-27 00:00:00
abstract::Alzheimer's disease (AD) is a multifactorial neurological condition associated with a genetic profile that is still not completely understood. In this study, using a whole gene microarray approach, we investigated age-dependent gene expression profile changes occurring in the hippocampus of young and old transgenic AD...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2014.11
更新日期:2014-02-13 00:00:00
abstract::As a key member of the forkhead box transcription factors, forkhead box F2 (FOXF2) serves as a transcriptional regulator and regulates downstream gene expression in embryonic development, metabolism and in some common diseases, such as stroke and gastroparesis. Recent studies have shown that aberrant expression of FOX...
journal_title:Cell death & disease
pub_type: 杂志文章,评审
doi:10.1038/s41419-020-2604-z
更新日期:2020-06-05 00:00:00
abstract::Gastric epithelial cells (GECs) provide the first point of contact of the host by Helicobacter pylori (H. pylori), and the interaction between H. pylori and GECs plays a critical role in H. pylori-associated diseases. Aberrant expression of transcription factors (TFs) contributes to the pathogenesis of inflammatory di...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-2705-8
更新日期:2020-07-01 00:00:00
abstract::Triple negative breast cancers (TNBC) are highly aggressive and lack specific targeted therapies. Recent studies have reported high expression of the transcription factor Kaiso in triple negative tumors, and this correlates with their increased aggressiveness. However, little is known about the clinical relevance of K...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2017.92
更新日期:2017-03-23 00:00:00
abstract::Colon cancer is one of the three common malignant tumors, with a lower survival rate. Ipatasertib, a novel highly selective ATP-competitive pan-Akt inhibitor, shows a strong antitumor effect in a variety of carcinoma, including colon cancer. However, there is a lack of knowledge about the precise underlying mechanism ...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-0943-9
更新日期:2018-09-05 00:00:00
abstract::Inflammasomes are multimeric protein complexes that assemble upon sensing of a variety of stress factors. Their formation results in caspase-1-mediated activation and secretion of the pro-inflammatory cytokines pro-interleukin(IL)-1β and -18, which induce an inflammatory response. Inflammation is supported by a lytic ...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-017-0009-4
更新日期:2018-01-18 00:00:00