H2AX phosphorylation within the G1 phase after UV irradiation depends on nucleotide excision repair and not DNA double-strand breaks.
AuthorsMarti TM, Hefner E, Feeney L, Natale V, Cleaver JE
JournalProc Natl Acad Sci U S A
PubMed ID16788066
'The variant histone H2AX is phosphorylated in response to UV irradiation of primary human fibroblasts in a complex fashion that is radically different from that commonly reported after DNA double-strand breaks. H2AX phosphorylation after exposure to ionizing radiation produces foci, which are detectable by immunofluorescence microscopy and have been adopted ... More
Aberrant T cell differentiation in the absence of Dicer.
AuthorsMuljo SA, Ansel KM, Kanellopoulou C, Livingston DM, Rao A, Rajewsky K
JournalJ Exp Med
PubMed ID16009718
'Dicer is an RNaseIII-like enzyme that is required for generating short interfering RNAs and microRNAs. The latter have been implicated in regulating cell fate determination in invertebrates and vertebrates. To test the requirement for Dicer in cell-lineage decisions in a mammalian organism, we have generated a conditional allele of dicer-1 ... More
Nuclear relocation of the nephrin and CD2AP-binding protein dendrin promotes apoptosis of podocytes.
AuthorsAsanuma K, Campbell KN, Kim K, Faul C, Mundel P
JournalProc Natl Acad Sci U S A
PubMed ID17537921
'Kidney podocytes and their slit diaphragms (SDs) form the final barrier to urinary protein loss. There is mounting evidence that SD proteins also participate in intracellular signaling pathways. The SD protein nephrin serves as a component of a signaling complex that directly links podocyte junctional integrity to actin cytoskeletal dynamics. ... More
An anti-transferrin receptor-avidin fusion protein exhibits both strong proapoptotic activity and the ability to deliver various molecules into cancer cells.
AuthorsNg PP, Dela Cruz JS, Sorour DN, Stinebaugh JM, Shin SU, Shin DS, Morrison SL, Penichet ML
JournalProc Natl Acad Sci U S A
PubMed ID12149472
'We have developed an antibody fusion protein (anti-rat TfR IgG3-Av) with the ability to deliver different molecules into cancer cells. It consists of avidin genetically fused to the C(H)3 region of a human IgG3 specific for the rat transferrin receptor. It forms strong, noncovalent interactions with biotinylated molecules such as ... More
Protein kinase Cepsilon activates protein kinase B/Akt via DNA-PK to protect against tumor necrosis factor-alpha-induced cell death.
AuthorsLu D, Huang J, Basu A
JournalJ Biol Chem
PubMed ID16785234
'We have previously shown that protein kinase Cepsilon (PKCepsilon) protects breast cancer cells from tumor necrosis factor-alpha (TNF)-induced cell death. In the present study, we have investigated if the antiapoptotic function of PKCepsilon is mediated via Akt and the mechanism by which PKCepsilon regulates Akt activity. TNF caused a transient ... More
Synthesis and identification of small molecules that potently induce apoptosis in melanoma cells through G1 cell cycle arrest.
'Late-stage malignant melanoma is a cancer that is refractory to current chemotherapeutic treatments. The average survival time for patients with such a diagnosis is 6 months. In general, the vast majority of anticancer drugs operate through induction of cell cycle arrest and cell death in either the DNA synthesis (S) ... More
ADP-ribosylation factor as a novel target for corneal neovascularization regression.
AuthorsDai C, Liu G, Li L, Xiao Y, Zhang X, Lu P
JournalMol Vis
PubMed ID23288987
To evaluate the roles of ADP-ribosylation factor (ARF) in alkali-induced corneal neovascularization (CNV).
Novel dipeptide nanoparticles for effective curcumin delivery.
AuthorsAlam S, Panda JJ, Chauhan VS
JournalInt J Nanomedicine
PubMed ID22915849
Curcumin, the principal curcuminoid of the popular Indian spice turmeric, has a wide spectrum of pharmaceutical properties such as antitumor, antioxidant, antiamyloid, and anti-inflammatory activity. However, poor aqueous solubility and low bioavailability of curcumin is a major challenge in its development as a useful drug. To enhance the aqueous solubility ... More
High-throughput screening of cell death inducible short peptides from TNF-related apoptosis-inducing ligand sequence.
AuthorsOkochi M, Nakanishi M, Kato R, Kobayashi T, Honda H
JournalFEBS Lett
PubMed ID16427631
Therapeutic peptides and small molecules, rationally designed to trigger cell death have attracted strong attention. Cell death inducible peptides were screened from amino acid sequence of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Using Fmoc solid phase synthesis, cellulose membrane-bound octameric peptide library of TRAIL scan was prepared and cell viability ... More
New inhibitors of prion replication that target the amyloid precursor.
AuthorsCharvériat M, Reboul M, Wang Q, Picoli C, Lenuzza N, Montagnac A, Nhiri N, Jacquet E, Guéritte F, Lallemand JY, Deslys JP, Mouthon F,
JournalJ Gen Virol
PubMed ID19264641
At present, there is no effective therapy for any of the neurodegenerative amyloidoses, despite renewed efforts to identify compounds active against the various implicated pathogenetic molecules. We have screened a library of 2960 natural and synthetic compounds in two cell lines chronically infected with mouse prions, and have identified eight ... More
Conventional apoptosis assays using propidium iodide generate a significant number of false positives that prevent accurate assessment of cell death.
AuthorsRieger AM, Hall BE, Luong le T, Schang LM, Barreda DR,
JournalJ Immunol Methods
PubMed ID20381494
The advent of flow cytometry-based applications has significantly impacted the study of cellular apoptosis. Propidium iodide (PI) is a commonly used viability stain in these studies. Unfortunately, we find that conventional Annexin V/PI protocols lead to a significant number of false positive events (up to 40%), which are associated with ... More
AuthorsSimard JM, Chen M, Tarasov KV, Bhatta S, Ivanova S, Melnitchenko L, Tsymbalyuk N, West GA, Gerzanich V
JournalNat Med
PubMed ID16550187
Pathological conditions in the central nervous system, including stroke and trauma, are often exacerbated by cerebral edema. We recently identified a nonselective cation channel, the NC(Ca-ATP) channel, in ischemic astrocytes that is regulated by sulfonylurea receptor 1 (SUR1), is opened by depletion of ATP and, when opened, causes cytotoxic edema. ... More
AuthorsWen Z, Pyeon D, Wang Y, Lambert P, Xu W, Ahlquist P
JournalMol Cell Biol
PubMed ID22025681
Since inactivation of tumor suppressor p53 functions is one of the most common features of human cancer cells, restoring p53 expression and activity is an important focus in cancer therapy. Here we report identification of photoreceptor-specific nuclear receptor (PNR)/NR2E3 as a positive regulator of p53 in a high-throughput genetic screen. ... More
Cholesterol-induced macrophage apoptosis requires ER stress pathways and engagement of the type A scavenger receptor.
AuthorsDevries-Seimon T, Li Y, Yao PM, Stone E, Wang Y, Davis RJ, Flavell R, Tabas I
JournalJ Cell Biol
PubMed ID16203857
Macrophage death in advanced atherosclerosis promotes necrosis and plaque destabilization. A likely cause of macrophage death is accumulation of free cholesterol (FC) in the ER, leading to activation of the unfolded protein response (UPR) and C/EBP homologous protein (CHOP)-induced apoptosis. Here we show that p38 MAPK signaling is necessary for ... More
Early and late cytotoxic effects of external application of the Alzheimer's Abeta result from the initial formation and function of Abeta ion channels.
AuthorsSimakova O, Arispe NJ
JournalBiochemistry
PubMed ID16669633
Extracellular application of the Alzheimer's beta-amyloid (Abeta) peptide evokes a series of cellular responses that leads to the death of cells by apoptosis. Some responses to freshly prepared Abeta occur immediately, including changes in intracellular calcium concentration and changes in membrane permeability and phosphatidylserine asymmetry. We show here that the ... More
Amyloid fibrils of mammalian prion protein are highly toxic to cultured cells and primary neurons.
AuthorsNovitskaya V, Bocharova OV, Bronstein I, Baskakov IV
JournalJ Biol Chem
PubMed ID16554307
A growing body of evidence indicates that small, soluble oligomeric species generated from a variety of proteins and peptides rather than mature amyloid fibrils are inherently highly cytotoxic. Here, we show for the first time that mature amyloid fibrils produced from full-length recombinant mammalian prion protein (rPrP) were highly toxic ... More
Exposure to airborne particulate matter (PM) is a world-wide health problem mainly because it produces adverse cardiovascular and respiratory effects that frequently result in morbidity. Despite many years of epidemiological and basic research, the mechanisms underlying PM toxicity remain largely unknown. To understand some of these mechanisms, we measured PM-induced ... More
Therapeutic effects of NK-HDAC-1, a novel histone deacetylase inhibitor, on collagen-induced arthritis through the induction of apoptosis of fibroblast-like synoviocytes.
AuthorsLi M, Liu X, Sun X, Wang Z, Guo W, Hu F, Yao H, Cao X, Jin J, Wang PG, Shen J, Li Z
JournalInflammation
PubMed ID23549599
The purpose of this study is to investigate the therapeutic effects of a novel histone deacetylase inhibitor (HDACi), NK-HDAC-1, on collagen-induced arthritis (CIA) and pathogenic fibroblast-like synoviocytes (FLSs) from patients with rheumatoid arthritis (RA). The proliferation and apoptosis of FLSs treated with NK-HDAC-1 were evaluated by flow cytometry and fluorescence ... More
The B subunit of an AB5 toxin produced by Salmonella enterica serovar Typhi up-regulates chemokines, cytokines, and adhesion molecules in human macrophage, colonic epithelial, and brain microvascular endothelial cell lines.
The principal function of bacterial AB5 toxin B subunits is to interact with glycan receptors on the surfaces of target cells and mediate the internalization of holotoxin. However, B subunit-receptor interactions also have the potential to impact cell signaling pathways and, in so doing, contribute to pathogenesis independently of the ... More
CDC7-dependent transcriptional regulation of RAD54L is essential for tumorigenicity and radio-resistance of glioblastoma.
AuthorsLi Q, Xie W, Wang N, Li C, Wang M
JournalTransl Oncol
PubMed ID29413763
'Accumulating evidence indicates that cell division cycle 7-related protein kinase(CDC7) plays an essential role in tumor cells and it could induces cell proliferation and could be related to prognosis in multiple types of cancer. However, the biological role and molecular mechanism of CDC7 in GBM still remains unclear. In this ... More
Targets Fishing and Identification of Calenduloside E as Hsp90AB1: Design, Synthesis, and Evaluation of Clickable Activity-Based Probe.
AuthorsWang S, Tian Y, Zhang JY, Xu HB, Zhou P, Wang M, Lu SB, Luo Y, Wang M, Sun GB, Xu XD, Sun XB
JournalFront Pharmacol
PubMed ID29875664
'Calenduloside E (CE), a natural triterpenoid compound isolated from'
Replacing plasma membrane outer leaflet lipids with exogenous lipid without damaging membrane integrity.
AuthorsLi G, Kakuda S, Suresh P, Canals D, Salamone S, London E
JournalPLoS One
PubMed ID31589646
We recently introduced a MaCD-based method to efficiently replace virtually the entire population of plasma membrane outer leaflet phospholipids and sphingolipids of cultured mammalian cells with exogenous lipids (Li et al, (2016) Proc. Natl. Acad. Sci USA 113:14025-14030). Here, we show if the lipid-to- MaCD ratio is too high or ... More