The human Tp53 Arg72Pro polymorphism explains different functional prognosis in stroke.
AuthorsGomez-Sanchez JC, Delgado-Esteban M, Rodriguez-Hernandez I, Sobrino T, Perez de la Ossa N, Reverte S, Bolaños JP, Gonzalez-Sarmiento R, Castillo J, Almeida A,
JournalJ Exp Med
PubMed ID21357744
'The functional outcome after stroke is unpredictable; it is not accurately predicted by clinical pictures upon hospital admission. The presence of apoptotic neurons in the ischemic penumbra and perihematoma area may account for poor prognosis, but whether the highly variable stroke outcome reflects differences in genetic susceptibility to apoptosis is ... More
Bocavirus infection induces mitochondrion-mediated apoptosis and cell cycle arrest at G2/M phase.
AuthorsChen AY, Luo Y, Cheng F, Sun Y, Qiu J,
JournalJ Virol
PubMed ID20335259
'Bocavirus is a newly classified genus of the family Parvovirinae. Infection with Bocavirus minute virus of canines (MVC) produces a strong cytopathic effect in permissive Walter Reed/3873D (WRD) canine cells. We have systematically characterized the MVC infection-produced cytopathic effect in WRD cells, namely, the cell death and cell cycle arrest, ... More
TWEAK induces apoptosis through a death-signaling complex comprising receptor-interacting protein 1 (RIP1), Fas-associated death domain (FADD), and caspase-8.
AuthorsIkner A, Ashkenazi A,
JournalJ Biol Chem
PubMed ID21525013
'The tumor necrosis factor (TNF) superfamily member TNF-like weak inducer of apoptosis (TNFSF12, CD255) (TWEAK) can stimulate apoptosis in certain cancer cells. Previous studies suggest that TWEAK activates cell death indirectly, by inducing TNFa-mediated autocrine signals. However, the underlying death-signaling mechanism has not been directly defined. Consistent with earlier work, ... More
Profiling of toxicity and identification of distinct apoptosis profiles using a 384-well high-throughput flow cytometry screening platform.
AuthorsLuu YK, Rana P, Duensing TD, Black C, Will Y,
JournalJ Biomol Screen
PubMed ID22496094
'Methods and techniques used to detect apoptosis have benefited from advances in technologies such as flow cytometry. With a large arsenal of lasers, fluorescent labels, and readily accessible biological targets, it is possible to detect multiple targets with unique combinations of fluorescent spectral signatures from a single sample. Traditional flow ... More
Parallel high-throughput RNA interference screens identify PINK1 as a potential therapeutic target for the treatment of DNA mismatch repair-deficient cancers.
AuthorsMartin SA, Hewish M, Sims D, Lord CJ, Ashworth A,
JournalCancer Res
PubMed ID21242281
Synthetic lethal approaches to cancer treatment have the potential to deliver relatively large therapeutic windows and therefore significant patient benefit. To identify potential therapeutic approaches for cancers deficient in DNA mismatch repair (MMR), we have carried out parallel high-throughput RNA interference screens using tumor cell models of MSH2- and MLH1-related ... More
Activation of caspase-9, but not caspase-2 or caspase-8, is essential for heat-induced apoptosis in Jurkat cells.
AuthorsShelton SN, Dillard CD, Robertson JD,
JournalJ Biol Chem
PubMed ID20978129
Exposure of cells to hyperthermia is known to induce apoptosis, although the underlying mechanisms are only partially understood. Here, we examine the molecular requirements necessary for heat-induced apoptosis using genetically modified Jurkat T-lymphocytes. Cells stably overexpressing Bcl-2/Bcl-x(L) or stably depleted of Apaf-1 were completely resistant to heat-induced apoptosis, implicating the ... More
Curcumin stimulates reactive oxygen species production and potentiates apoptosis induction by the antitumor drugs arsenic trioxide and lonidamine in human myeloid leukemia cell lines.
AuthorsSánchez Y, Simón GP, Calviño E, de Blas E, Aller P,
JournalJ Pharmacol Exp Ther
PubMed ID20605902
Arsenic trioxide (ATO, Trisenox) is an important antileukemic drug, but its efficacy is frequently low when used as a single agent. Here, we demonstrate that the apoptotic action of ATO is greatly increased when combined with subcytotoxic curcumin concentrations in U937 and HL60 human acute myeloid leukemia cells, and with ... More
Rem2 GTPase maintains survival of human embryonic stem cells as well as enhancing reprogramming by regulating p53 and cyclin D1.
AuthorsEdel MJ, Menchon C, Menendez S, Consiglio A, Raya A, Izpisua Belmonte JC,
JournalGenes Dev
PubMed ID20231315
Human pluripotent stem cells, such as embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs), have the unique abilities of differentiation into any cell type of the organism (pluripotency) and indefinite self-renewal. Here, we show that the Rem2 GTPase, a suppressor of the p53 pathway, is up-regulated in hESCs ... More
13q14 deletions in CLL involve cooperating tumor suppressors.
AuthorsPalamarchuk A, Efanov A, Nazaryan N, Santanam U, Alder H, Rassenti L, Kipps T, Croce CM, Pekarsky Y,
JournalBlood
PubMed ID20071661
B-cell chronic lymphocytic leukemia (CLL) is the most common human leukemia. 13q14 deletions are most common chromosomal alterations in CLL. We previously reported that miR-15/16 is a target of 13q14 deletions and plays a tumor suppressor role by targeting BCL2. Because DLEU7 is located near miR-15/16 and is also positioned ... More
Energy depletion inhibits phosphatidylinositol 3-kinase/Akt signaling and induces apoptosis via AMP-activated protein kinase-dependent phosphorylation of IRS-1 at Ser-794.
AuthorsTzatsos A, Tsichlis PN
JournalJ Biol Chem
PubMed ID17459875
Energy depletion activates AMP-activated protein kinase (AMPK) and inhibits cell growth via TSC2-dependent suppression of mTORC1 signaling. Long term energy depletion also induces apoptosis by mechanisms that are not well understood to date. Here we show that AMPK, activated by energy depletion, inhibited cell survival by binding to and phosphorylating ... More
Interrelated roles for Mcl-1 and BIM in regulation of TRAIL-mediated mitochondrial apoptosis.
AuthorsHan J, Goldstein LA, Gastman BR, Rabinowich H
JournalJ Biol Chem
PubMed ID16478725
The current study demonstrates a novel cross-talk mechanism between the TRAIL receptor death signaling pathway and the mitochondria. This newly identified pathway is regulated at the mitochondrial outer membrane by a complex between the prosurvival Bcl-2 member, Mcl-1 and the BH3-only protein, Bim. Under non-apoptotic conditions, Bim is sequestered by ... More
Mitochondrial Membrane Potential-dependent Endoplasmic Reticulum Fragmentation is an Important Step in Neuritic Degeneration.
AuthorsBao FX, Shi HY, Long Q, Yang L, Wu Y, Ying ZF, Qin DJ, Zhang J, Guo YP, Li HM, Liu XG
JournalCNS Neurosci Ther
PubMed ID27080255
Neuritic degeneration is an important early pathological step in neurodegeneration.
Calpastatin overexpression reduces oxidative stress-induced mitochondrial impairment and cell death in human neuroblastoma SH-SY5Y cells by decreasing calpain and calcineurin activation, induction of mitochondrial fission and destruction of mitochondrial fusion.
AuthorsTangmansakulchai K, Abubakar Z, Kitiyanant N, Suwanjang W, Leepiyasakulchai C, Govitrapong P, Chetsawang B
JournalMitochondrion
PubMed ID27453331
Calpain is an intracellular Ca(2+)-dependent protease, and the activation of calpain has been implicated in neurodegenerative diseases. Calpain activity can be regulated by calpastatin, an endogenous specific calpain inhibitor. Several lines of evidence have demonstrated a potential role of calpastatin in preventing calpain-mediated pathogenesis. Additionally, several studies have revealed that ... More
The effect of gallic acid on cytotoxicity, Ca(2+) homeostasis and ROS production in DBTRG-05MG human glioblastoma cells and CTX TNA2 rat astrocytes.
AuthorsHsu SS, Chou CT, Liao WC, Shieh P, Kuo DH, Kuo CC, Jan CR, Liang WZ
JournalChem Biol Interact
PubMed ID27060209
Gallic acid, a polyhydroxylphenolic compound, is widely distributed in various plants, fruits and foods. It has been shown that gallic acid passes into blood brain barrier and reaches the brain tissue of middle cerebral artery occlusion rats. However, the effect of gallic acid on Ca(2+) signaling in glia cells is ... More
Cytotoxic effects of gastrodin extracted from the rhizome of Gastrodia elata Blume in glioblastoma cells, but not in normal astrocytes, via the induction of oxidative stress-associated apoptosis that involved cell cycle arrest and p53 activation.
AuthorsLiang WZ, Jan CR, Hsu SS
JournalFood Chem Toxicol
PubMed ID28689919
Researches have been conducted to explore the biological effect of gastrodin, a natural compound extracted from the rhizome of Gastrodia elata Blume, in different models. However, the effects of gastrodin on cytotoxicity, cell cycle distribution and oxidative stress in glia cells have not been explored. The aim of this study ... More
In vitro cytotoxicity of L-amino acid oxidase from the venom of Crotalus mitchellii pyrrhus.
AuthorsTan KK, Ler SG, Gunaratne J, Bay BH, Ponnampalam G
JournalToxicon
PubMed ID28943466
L-amino acid oxidase isolated from Crotalus mitchellii pyrrhus (Cmp-LAAO) exhibited cytotoxicity against LNCaP prostate adenocarcinoma cells. The viability of LNCaP cells decreased in a concentration- and time-dependent manner upon administration of Cmp-LAAO. Cmp-LAAO induced apoptosis as evidenced by AnnexinV/PI staining using flow cytometry. An increase in caspase-9 and caspase-3 activity ... More
Lapachol acetylglycosylation enhances its cytotoxic and pro-apoptotic activities in HL60 cells.
AuthorsMarques LB, Ottoni FM, Pinto MCX, Ribeiro JM, de Sousa FS, Weinlich R, de Victo NC, Kisitu J, Holzer AK, Leist M, Alves RJ, Souza-Fagundes EM
JournalToxicol In Vitro
PubMed ID31935485
Lapachol is a plant-derived naphthoquinone that kills several types of cancer cells. Derivatives of this molecule may therefore prove to be useful chemotherapeutic agents. In this study, we explored whether glycosylation increases the cytotoxic potency of lapachol towards HL-60 human leukemia cells. Two beta-glycosides were synthesized and characterized: LA4A (lapachol-ß-glucoside) ... More