Abstract:
:Spermidine, a natural polyamine presented widely in mammalian cells, has been implicated to extend the lifespan of several model organisms by inducing autophagy. However, the effect of spermidine against neuronal damage has not yet been fully determined. In this study, neuronal cell injury was induced by treating PC12 cells and cortical neurons with 1 μM staurosporine (STS). We found that STS-induced cell injury could be efficiently attenuated by pretreatment with 1 mM spermidine. Spermidine inhibited the caspase 3 activation induced by STS. Moreover, STS incubation resulted in autophagic degradation failure, which could be attenuated by the pretreatment of spermidine. Knocking down the expression of Beclin 1 efficiently suppressed autophagosome and autolysosome accumulation, and abolished the protective effects of spermidine against STS-induced neurotoxicity. Increased Beclin 1 cleavage and partial nuclear translocation of Beclin 1 fragment was detected in STS-treated cells, which could be blocked by spermidine, pan-caspase inhibitor or caspase 3-specific inhibitor. The nuclear translocation of Beclin 1 fragment universally occurs in damaged neurons. Beclin 1 mutation at the sites of 146 and 149 prevented the intracellular re-distribution of Beclin 1 induced by STS. In addition, intraperitoneal injection of spermidine ameliorated ischemia/reperfusion-induced neuronal injury in the hippocampus and cortex of rats, possibly via blocking caspase 3 activation and consequent Beclin 1 cleavage. Our findings suggest that caspase 3-mediated Beclin 1 cleavage occurs in acute neuronal cell injury both in vitro and in vivo. The neuroprotective effect of spermidine may be related to inhibition of the caspase 3-mediated Beclin 1 cleavage and restoration of the Beclin 1-dependent autophagy.
journal_name
Cell Death Disjournal_title
Cell death & diseaseauthors
Yang Y,Chen S,Zhang Y,Lin X,Song Y,Xue Z,Qian H,Wang S,Wan G,Zheng X,Zhang Ldoi
10.1038/cddis.2017.161subject
Has Abstractpub_date
2017-04-06 00:00:00pages
e2738issue
4issn
2041-4889pii
cddis2017161journal_volume
8pub_type
杂志文章abstract::Glioma patients commonly suffer from epileptic seizures. However, the mechanisms of glioma-associated epilepsy are far to be completely understood. Using glioma-neurons co-cultures, we found that tumor cells are able to deeply influence neuronal chloride homeostasis, by depolarizing the reversal potential of γ-aminobu...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2014.437
更新日期:2014-10-30 00:00:00
abstract::The formulation of quercetin nanoliposomes (QUE-NLs) has been shown to enhance QUE antitumor activity in C6 glioma cells. At high concentrations, QUE-NLs induce necrotic cell death. In this study, we probed the molecular mechanisms of QUE-NL-induced C6 glioma cell death and examined whether QUE-NL-induced programmed c...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2013.242
更新日期:2013-08-01 00:00:00
abstract::Peroxisome proliferator-activated receptor gamma (PPARγ) is a key regulator of adipocyte differentiation and has an important role in metabolic syndrome. Phosphorylation of the receptor's ligand-binding domain at serine 273 has been shown to change the expression of a large number of genes implicated in obesity. The d...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2011.74
更新日期:2011-08-11 00:00:00
abstract::Cellular acetylation homeostasis is a kinetic balance precisely controlled by histone acetyl-transferase (HAT) and histone deacetylase (HDAC) activities. The loss of the counterbalancing function of basal HAT activity alters the precious HAT:HDAC balance towards enhanced histone deacetylation, resulting in a loss of a...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2016.465
更新日期:2017-01-26 00:00:00
abstract::Increasing the sensitivity of glioblastoma cells to radiation is a promising approach to improve survival in patients with glioblastoma multiforme (GBM). This study aims to determine if serine/threonine phosphatase (protein phosphatase 6 (PP6)) is a molecular target for GBM radiosensitization treatment. The GBM orthot...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2011.126
更新日期:2011-12-08 00:00:00
abstract::While TRAIL is a promising anticancer agent due to its ability to selectively induce apoptosis in neoplastic cells, many tumors, including pancreatic ductal adenocarcinoma (PDA), display intrinsic resistance, highlighting the need for TRAIL-sensitizing agents. Here we report that TRAIL-induced apoptosis in PDA cell li...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2014.102
更新日期:2014-03-27 00:00:00
abstract::Proteases modulate critical processes in cutaneous tissue repair to orchestrate inflammation, cell proliferation and tissue remodeling. However, the functional consequences and implications in healing impairments of most cleavage events are not understood. Using iTRAQ-based Terminal Amine Isotopic Labeling of Substrat...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-02883-2
更新日期:2020-08-21 00:00:00
abstract::DNA damage regulated autophagy modulator 1 (DRAM1) is a stress-inducible regulator of autophagy and cell death. DRAM1 has been implicated in cancer, myocardial infarction, and infectious diseases, but the molecular and cellular functions of this transmembrane protein remain poorly understood. Previously, we have propo...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-2477-1
更新日期:2020-04-24 00:00:00
abstract::African swine fever virus (ASFV) infection induces apoptosis in the infected cell; however, the consequences of this activation on virus replication have not been defined. In order to identify the role of apoptosis in ASFV infection, we analyzed caspase induction during the infection and the impact of caspase inhibiti...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2012.81
更新日期:2012-07-05 00:00:00
abstract::Mammalian female fertility is limited by the number and quality of oocytes in the ovarian reserve. The number of oocytes is finite since all germ cells cease proliferation to become oocytes in fetal life. Moreover, 70-80% of the initial oocyte population is eliminated during fetal and neonatal development, restricting...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-2019-x
更新日期:2019-10-17 00:00:00
abstract::miRNAs are involved in many physiologic and disease processes by virtue of degrading specific mRNAs or inhibiting their translation. miR-148a has been implicated in the control of tumor growth and cholesterol and triglyceride homeostasis using in vitro or in vivo gene expression- and silencing-based approaches. Here m...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2017.309
更新日期:2017-07-13 00:00:00
abstract::The injurious consequences of ionizing radiation (IR) to normal human cells and the acquired radioresistance of cancer cells represent limitations to cancer radiotherapy. IR induces DNA damage response pathways that orchestrate cell cycle arrest, DNA repair or apoptosis such that irradiated cells are either repaired o...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2011.3
更新日期:2011-02-10 00:00:00
abstract::Platelets enhance thrombin generation at sites of vascular injury by exposing phosphatidylserine during necrosis-like cell death. Anoctamin 6 (Ano6) is required for Ca(2+)-dependent phosphatidylserine exposure and is defective in patients with Scott syndrome, a rare bleeding disorder. Ano6 may also form Cl(-) channels...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2013.495
更新日期:2013-12-19 00:00:00
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
更新日期:2020-11-11 00:00:00
abstract::Lipid rafts and mitochondria are promising targets in cancer therapy. The synthetic antitumor alkyl-lysophospholipid analog edelfosine (1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine) has been reported to target lipid rafts. Here, we have found that edelfosine induced loss of mitochondrial membrane potential an...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2011.41
更新日期:2011-05-19 00:00:00
abstract::Numerous evidences have shown that circular RNAs (circRNAs) play a key role in regulating the pathogenesis of cancer. However, the mechanism of circRNAs in urothelial carcinoma of bladder (UCB) remains largely unclear. In this study, we found circFAM114A2 was significantly downregulated both in UCB tissue specimens an...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-2226-5
更新日期:2020-01-22 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::Cognitive aging is a leading public health concern with the increasing aging population, but there is still lack of specific interventions directed against it. Recent studies have shown that cognitive function is intimately affected by systemic milieu in aging brain, and improvement of systemic environment in aging br...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2017.316
更新日期:2017-08-10 00:00:00
abstract::Mitogen-activated protein kinases (MAPKs) are conserved protein kinases that regulate a variety of important cellular signaling pathways. Among them, c-Jun N-terminal kinases (JNK) are known to be activated by various environmental stresses including virus infections. Previously, activation of the JNK pathway has been...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-017-0053-0
更新日期:2017-12-13 00:00:00
abstract::Tumor-associated macrophages (TAMs) are frequently found near pancreatic cancer cells, but it is uncertain whether they are involved in pancreatic cancer progression and the Warburg effect. Here, we show that CCL18 secreted by TAMs facilitates malignant progression and induced a glycolytic phenotype in pancreatic canc...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-0486-0
更新日期:2018-05-01 00:00:00
abstract::Autophagy is a pivotal intracellular process by which cellular macromolecules are degraded upon various stimuli. A failure in the degradation of autophagic substrates such as impaired organelles and protein aggregates leads to their accumulations, which are characteristics of many neurodegenerative diseases. Pharmacol...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2017.501
更新日期:2017-10-05 00:00:00
abstract::Activation of Ras-related C3 botulinum toxin substrate 1 (Rac1) has been implicated in diverse kidney diseases, yet its in vivo significance in diabetic nephropathy (DN) is largely unknown. In the present study, we demonstrated a podocyte-specific Rac1-deficient mouse strain and showed that specific inhibition of Rac1...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-0353-z
更新日期:2018-03-01 00:00:00
abstract::Spermatogenesis associated serine rich 2 (SPATS2) has been reported to contribute to the tumorigenesis of multiple malignancies. The molecular function of SPATS2 in hepatocellular carcinoma (HCC) is still not fully understood. In this study, we aimed to investigate the expression pattern and function roles of SPATS2 i...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-03039-y
更新日期:2020-10-09 00:00:00
abstract::The enteric pathogen enterohemorrhagic Escherichia coli (EHEC) is responsible for outbreaks of bloody diarrhea and hemolytic uremic syndrome (HUS) worldwide. Several molecular mechanisms have been described for the pathogenicity of EHEC; however, the role of bacterial metabolism in the virulence of EHEC during infecti...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-0423-2
更新日期:2018-03-07 00:00:00
abstract::Glioblastoma multiform (GBM) is the most common brain tumor characterized by a dismal prognosis. GBM cancer stem cells (gCSC) or tumor-initiating cells are the cell population within the tumor-driving therapy resistance and recurrence. While temozolomide (TMZ), an alkylating agent, constitutes the first-line chemother...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-1477-5
更新日期:2019-03-13 00:00:00
abstract::Following stroke-induced neuronal damage, quiescent oligodendrocyte precursors (OPCs) are activated to proliferate and later to differentiate to myelin-producing cells. GPR17, a receptor transiently expressed on early OPCs, has emerged as a target to implement stroke repair through stimulation of OPC maturation. Howev...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2017.256
更新日期:2017-06-08 00:00:00
abstract::Mechanisms underlying the generation of induced pluripotent stem cells (iPSC) and keeping iPSC stability remain to be further defined. Accumulated evidences showed that iPSC reprogramming may be controlled by the cell-division-rate-dependent model. Here we reported effects of absence of mouse p27 or p18 on iPSC genera...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-1502-8
更新日期:2019-03-20 00:00:00
abstract::Senescence is an antiproliferative mechanism that can suppress tumor development and can be induced by oncogenes such as genes of the Ras family. Although studies have implicated bioactive sphingolipids (SL) in senescence, the specific mechanisms remain unclear. Here, using MCF10A mammary epithelial cells, we demonstr...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-03281-4
更新日期:2021-01-04 00:00:00
abstract::The aim of the present report was to investigate whether, in the mammalian spinal cord, cell death induced by transient excitotoxic stress could trigger activation and proliferation of endogenous neuroprogenitor cells as a potential source of a lesion repair process and the underlying time course. Because it is diffic...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2013.431
更新日期:2013-10-31 00:00:00
abstract::Metastasis is the leading cause of death for colorectal cancer (CRC). However, the protein transport process involved in CRC metastasis remains unclear. In this report, we use whole-exome sequencing and bioinformatics analysis to identify somatic mutations in CRC samples and found mutations of the protein transport ge...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-2358-7
更新日期:2020-03-02 00:00:00