Degradation of heparan sulfate proteoglycans enhances oxidized-LDL-mediated autophagy and apoptosis in human endothelial cells.
AuthorsDing Z, Wang X, Khaidakov M, Liu S, Dai Y, Mehta JL,
JournalBiochem Biophys Res Commun
PubMed ID22910414
Cell surface heparan sulfate proteoglycans (HSPG) play an important role in atherogenesis. We hypothesized that degradation of HSPG may increase the binding of atherogenic oxidized low density lipoprotein (ox-LDL) to endothelial cells, and result in extensive HSPG degradation as well as autophagy and apoptosis. Primary human umbilical vein endothelial cells ... More
MST1 functions as a key modulator of neurodegeneration in a mouse model of ALS.
'Amyotrophic lateral sclerosis (ALS) is an adult-onset neurodegenerative disorder characterized by loss of motor neurons. Dominant mutations in the gene for superoxide dismutase 1 (SOD1) give rise to familial ALS by an unknown mechanism. Here we show that genetic deficiency of mammalian sterile 20-like kinase 1 (MST1) delays disease onset ... More
SLC33A1/AT-1 Protein Regulates the Induction of Autophagy Downstream of IRE1/XBP1 Pathway.
AuthorsPehar M, Jonas MC, Hare TM, Puglielli L,
JournalJ Biol Chem
PubMed ID22787145
'One of the main functions of the unfolded protein response is to ensure disposal of large protein aggregates that accumulate in the lumen of the endoplasmic reticulum (ER) whereas avoiding, at least under nonlethal levels of ER stress, cell death. When tightly controlled, autophagy-dependent ER-associated degradation (ERAD(II)) allows the cell ... More
AUTOCOUNTER, an ImageJ JavaScript to analyze LC3B-GFP expression dynamics in autophagy-induced astrocytoma cells.
AuthorsFassina L, Magenes G, Inzaghi A, Palumbo S, Allavena G, Miracco C, Pirtoli L, Biggiogera M, Comincini S,
JournalEur J Histochem
PubMed ID23361240
'An ImageJ JavaScript, AUTOCOUNTER, was specifically developed to monitor and measure LC3B-GFP expression in living human astrocytoma cells, namely T98G and U373-MG. Discrete intracellular GFP fluorescent spots derived from transduction of a Baculovirus replication-defective vector (BacMam LC3B-GFP), followed by microscope examinations at different times. After viral transgene expression, autophagy was ... More
Combining imaging and pathway profiling: an alternative approach to cancer drug discovery.
AuthorsCarragher NO, Brunton VG, Frame MC,
JournalDrug Discov Today
PubMed ID22493783
Conventional drug discovery strategies are typically 'target centric' based on the selection of lead compounds with optimised 'on-target' potency and selectivity profiles. However, high-attrition rates are often the result of compensatory or redundant cancer mechanisms and the fact that tumours do not find it difficult to escape inhibition of a ... More
microRNA-17 regulates the expression of ATG7 and modulates the autophagy process, improving the sensitivity to temozolomide and low-dose ionizing radiation treatments in human glioblastoma cells.
ATG7 is a key autophagy-promoting gene that plays a critical role in the regulation of cell death and survival of various cell types. We report here that microRNAs (miRNAs), a class of endogenous 22-24 nucleotide noncoding RNA molecules able to affect stability and translation of mRNA, may represent a novel ... More
Most anti-BrdU antibodies react with 2'-deoxy-5-ethynyluridine -- the method for the effective suppression of this cross-reactivity.
AuthorsLiboska R, Ligasová A, Strunin D, Rosenberg I, Koberna K,
JournalPLoS One
PubMed ID23272138
5-Bromo-2'-deoxyuridine (BrdU) and 2'-deoxy-5-ethynyluridine (EdU) are widely used as markers of replicated DNA. While BrdU is detected using antibodies, the click reaction typically with fluorescent azido-dyes is used for EdU localisation. We have performed an analysis of ten samples of antibodies against BrdU with respect to their reactivity with EdU. ... More
Downregulation of protein kinase CK2 induces autophagic cell death through modulation of the mTOR and MAPK signaling pathways in human glioblastoma cells.
AuthorsOlsen BB, Svenstrup TH, Guerra B,
JournalInt J Oncol
PubMed ID23007634
Glioblastoma multiforme is the most common primary brain tumor and one of the most aggressive types of cancer in adults. Survival signaling and apoptosis resistance are hallmarks of malignant glioma cells. However, recent studies have shown that other types of cell death such as autophagy can be induced in malignant ... More
Different involvement of autophagy in human malignant glioma cell lines undergoing irradiation and temozolomide combined treatments.
AuthorsPalumbo S, Pirtoli L, Tini P, Cevenini G, Calderaro F, Toscano M, Miracco C, Comincini S,
JournalJ Cell Biochem
PubMed ID22345070
Glioblastoma (GB) has a poor prognosis, despite current multimodality treatment. Beside surgical resection, adjuvant ionizing radiation (IR) combined with Temozolomide (TMZ) drug administration is the standard therapy for GB. This currently combined radio-chemotherapy treatment resulted in glial tumor cell death induction, whose main molecular death pathways are still not completely ... More
Shiga toxins induce autophagy leading to differential signalling pathways in toxin-sensitive and toxin-resistant human cells.
The bacterial virulence factors Shiga toxins (Stxs) are expressed by Shigella dysenteriae serotype 1 and certain Escherichia coli strains. Stxs are protein synthesis inhibitors and induce apoptosis in many cell types. Stxs induce apoptosis via prolonged endoplasmic reticulum stress signalling to activate both extrinsic and intrinsic pathways in human myeloid ... More
Long-term effectiveness of the Burch colposuspension in female urinary stress incontinence.
Of 91 women who underwent Burch colposuspension, 86 were available for clinical, urodynamic and isotope renographic follow-up examinations 5 years after surgery for evaluation of late complications and long-term effectiveness in urinary stress incontinence. A repeat urodynamic examination was accepted by 76 patients. Stress incontinence was cured in 71% of ... More
Screen for chemical modulators of autophagy reveals novel therapeutic inhibitors of mTORC1 signaling.
AuthorsBalgi AD, Fonseca BD, Donohue E, Tsang TC, Lajoie P, Proud CG, Nabi IR, Roberge M,
JournalPLoS One
PubMed ID19771169
BACKGROUND: Mammalian target of rapamycin complex 1 (mTORC1) is a protein kinase that relays nutrient availability signals to control numerous cellular functions including autophagy, a process of cellular self-eating activated by nutrient depletion. Addressing the therapeutic potential of modulating mTORC1 signaling and autophagy in human disease requires active chemicals with ... More
Mitochondria supply membranes for autophagosome biogenesis during starvation.
Starvation-induced autophagosomes engulf cytosol and/or organelles and deliver them to lysosomes for degradation, thereby resupplying depleted nutrients. Despite advances in understanding the molecular basis of this process, the membrane origin of autophagosomes remains unclear. Here, we demonstrate that, in starved cells, the outer membrane of mitochondria participates in autophagosome biogenesis. ... More
Deletion of PRKAA triggers mitochondrial fission by inhibiting the autophagy-dependent degradation of DNM1L.
Authors
JournalAutophagy
PubMed ID28085543
Impact on Autophagy and Ultraviolet B Induced Responses of Treatment with the MTOR Inhibitors Rapamycin, Everolimus, Torin 1, and pp242 in Human Keratinocytes.
AuthorsXu S, Li L, Li M, Zhang M, Ju M, Chen X, Gu H
JournalOxid Med Cell Longev
PubMed ID28400912
'The mechanistic target of Rapamycin (MTOR) protein is a crucial signaling regulator in mammalian cells that is extensively involved in cellular biology. The function of MTOR signaling in keratinocytes remains unclear. In this study, we detected the MTOR signaling and autophagy response in the human keratinocyte cell line HaCaT and ... More
WX20120108, a novel IAP antagonist, induces tumor cell autophagy via activating ROS-FOXO pathway.
AuthorsDing R, Wang X, Chen W, Li Z, Wei AL, Wang QB, Nie AH, Wang LL
JournalActa Pharmacol Sin
PubMed ID31316176
'Recently, inhibitor of apoptosis proteins (IAPs) and some IAP antagonists were found to regulate autophagy, but the underlying mechanisms remain unclear. WX20120108 is an analogue of GDC-0152 (a known IAP antagonist) and displays more potent anti-tumor and autophagy-regulating activity in tumor cells, we investigated the regulatory mechanisms underlying WX20120108-induced autophagy. ... More
Apoptosis and antitumor effects induced by the combination of an mTOR inhibitor and an autophagy inhibitor in human osteosarcoma MG63 cells.
AuthorsHorie R, Nakamura O, Yamagami Y, Mori M, Nishimura H, Fukuoka N, Yamamoto T
JournalInt J Oncol
PubMed ID26530936
'The inhibition of the mammalian target of rapamycin (mTOR) signaling pathway promotes the initiation of autophagy. Although it remains under debate whether chemotherapy-induced autophagy in tumor cells is a protective response or is invoked to promote cell death, recent studies indicate that autophagy is a self-defense mechanism of cancer cells ... More
Identification of compound CA-5f as a novel late-stage autophagy inhibitor with potent anti-tumor effect against non-small cell lung cancer.
Authors
JournalAutophagy
PubMed ID30145925
The integral membrane protein ITM2A, a transcriptional target of PKA-CREB, regulates autophagic flux via interaction with the vacuolar ATPase.
Authors
JournalAutophagy
PubMed ID25951193
Interleukin-6: a bone marrow stromal cell paracrine signal that induces neuroendocrine differentiation and modulates autophagy in bone metastatic PCa cells.
Authors
JournalAutophagy
PubMed ID22441019
Insights into autophagosome maturation revealed by the structures of ATG5 with its interacting partners.
Authors
JournalAutophagy
PubMed ID25484072
Autophagy fosters myofibroblast differentiation through MTORC2 activation and downstream upregulation of CTGF.
Authors
JournalAutophagy
PubMed ID25495560
AMPK promotes tolerance to Ras pathway inhibition by activating autophagy.
Authors
JournalOncogene
PubMed ID27041569
Accumulation of p62 in degenerated spinal cord under chronic mechanical compression: functional analysis of p62 and autophagy in hypoxic neuronal cells.
Authors
JournalAutophagy
PubMed ID22082874
A quantitative TR-FRET plate reader immunoassay for measuring autophagy.
Authors
JournalAutophagy
PubMed ID22622129
BNIP3L-mediated mitophagy is required for mitochondrial remodeling during the differentiation of optic nerve oligodendrocytes.
Authors
JournalAutophagy
PubMed ID33404293
Protective effects of lipoic acid against acrylamide-induced neurotoxicity: involvement of mitochondrial energy metabolism and autophagy.
AuthorsSong G, Liu Z, Wang L, Shi R, Chu C, Xiang M, Tian Q, Liu X
JournalFood Funct
PubMed ID29159335
Acrylamide (ACR) is a chronic neurotoxin that is generated in high-starch foods during heat processing. Alpha-lipoic acid (LA) is an antioxidant that occurs in most plants and animals. The objective of this study was to reveal the mechanism of ACR-triggered neurotoxicity and identify the protective role of LA in SH-SY5Y ... More
ATM signals to AMPK to promote autophagy and positively regulate DNA damage in response to cadmium-induced ROS in mouse spermatocytes.
AuthorsLi R, Luo X, Zhu Y, Zhao L, Li L, Peng Q, Ma M, Gao Y
JournalEnviron Pollut
PubMed ID28964605
Cadmium (Cd) is a toxic heavy metal and harmful to human health due to its ability to accumulate in organs. Previous studies have shown that Cd can induce DNA damage and autophagy. Autophagy can stabilize genetic material and DNA integrity. The aim of the present study was to determine the ... More
Up-regulation of the active form of small GTPase Rab13 promotes macroautophagy in vascular endothelial cells.
AuthorsZhang L, Dai F, Cui L, Zhou B, Guo Y
JournalBiochim Biophys Acta Mol Cell Res
PubMed ID28087344
The importance of macroautophagy (hereafter referred to as autophagy) in vascular endothelial cell (VEC) biology and dysfunction is increasingly recognized, but the molecular mechanisms of autophagy in VECs in the presence of serum are still poorly understood. Previously, we identified pterostilbene as a potent autophagy inducer of VECs in the ... More
Hypoxia induces apoptosis of mouse spermatocyte GC-2 cells through activation of autophagy.
AuthorsZhou J, Qian CY, Tong RQ, Wang B, Chen XL, Zhuang YY, Xia F, He Q, Lv JX
JournalCell Biol Int
PubMed ID29660204
The aim of this study was to investigate the underlying mechanisms of hypoxia-induced apoptosis of GC-2spd (GC-2) cells. The GC-2 cells were treated with or without hypoxia for 12, 24, 48, and 72?h. Apoptosis of GC-2 cells was detected using TUNEL and flow cytometry. Fluorescence microscopic was used to observe ... More
Resveratrol sensitizes lung cancer cell to TRAIL by p53 independent and suppression of Akt/NF-?B signaling.
AuthorsRasheduzzaman M, Jeong JK, Park SY
JournalLife Sci
PubMed ID30031063
TRAIL is a promising anticancer agent that has the potential to sensitize a wide variety of cancer or transformed cells by inducing apoptosis. However, resistance to TRAIL is a growing concern. Current manuscript aimed to employ combination treatment to investigate resveratrol induced TRAIL sensitization in NSCLC. ... More
Secretome of Differentiated PC12 Cells Restores the Monocrotophos-Induced Damages in Human Mesenchymal Stem Cells and SHSY-5Y Cells: Role of Autophagy and Mitochondrial Dynamics.
AuthorsSrivastava A, Singh S, Rajpurohit CS, Srivastava P, Pandey A, Kumar D, Khanna VK, Pant AB
JournalNeuromolecular Med
PubMed ID29603067
A perturbed cellular homeostasis is a key factor associated with xenobiotic exposure resulting in various ailments. The local cellular microenvironment enriched with secretory components aids in cell-cell communication that restores this homeostasis. Deciphering the underlying mechanism behind this restorative potential of secretome could serve as a possible solution to many ... More
Autophagy Impairment Is Associated With Increased Inflammasome Activation and Reversal Reaction Development in Multibacillary Leprosy.
Authorsde Mattos Barbosa MG, de Andrade Silva BJ, Assis TQ, da Silva Prata RB, Ferreira H, Andrade PR, da Paixão de Oliveira JA, Sperandio da Silva GM, da Costa Nery JA, Sarno EN, Pinheiro RO
JournalFront Immunol
PubMed ID29915584
Leprosy reactions are responsible for incapacities in leprosy and represent the major cause of permanent neuropathy. The identification of biomarkers able to identify patients more prone to develop reaction could contribute to adequate clinical management and the prevention of disability. Reversal reaction may occur in unstable borderline patients and also ... More
Apigenin restores impairment of autophagy and downregulation of unfolded protein response regulatory proteins in keratinocytes exposed to ultraviolet B radiation.
AuthorsLi L, Li M, Xu S, Chen H, Chen X, Gu H
JournalJ Photochem Photobiol B
PubMed ID30933875
Ultraviolet (UV)-B radiation is a major environmental risk factor that is responsible for the development and progression of many skin cancers. Apigenin, a type of bioflavonoid, has been reported to inhibit UVB-induced skin cancer. However, how apigenin functions in keratinocytes with UV damage remains unclear. In this study, by lactate ... More
Inhibition of Autophagy by Captopril Attenuates Prion Peptide-Mediated Neuronal Apoptosis via AMPK Activation.
AuthorsMoon JH, Jeong JK, Hong JM, Seol JW, Park SY
JournalMol Neurobiol
PubMed ID30288697
Accumulation of prion protein (PrPc) into a protease-resistant form (PrPsc) in the brains of humans and animals affects the central nervous system. PrPsc occurs only in mammals with transmissible prion diseases. Prion protein refers to either the infectious pathogen itself or the main component of the pathogen. Recent studies suggest ... More
High glucose disrupts autophagy lysosomal pathway in gingival epithelial cells via ATP6V0C.
AuthorsHuang X, Kuang S, Shen Z, Liang M, Lin Z
JournalJ Periodontol
PubMed ID31471894
Hyperglycemic micro-environment induced by diabetes could regulate the response of periodontal tissues to pathogenic microorganisms in which disruption of autophagy lysosomal pathway (ALP) may participate. This study aimed to explore the mechanisms underlying how high glucose (HG) regulates ALP in gingival epithelial cells (GECs). ... More