A5027367008- Autophagy in Disease and Therapy
- Calcium signaling and nucleotide metabolism
- Lysosomal Storage Disorders Research
- Galectins and Cancer Biology
- Cell death mechanisms and regulation
- Dermatology and Skin Diseases
- Ubiquitin and proteasome pathways
- Cellular transport and secretion
- Metabolism, Diabetes, and Cancer
- Sirtuins and Resveratrol in Medicine
- CRISPR and Genetic Engineering
- RNA Interference and Gene Delivery
- Heat shock proteins research
- thermodynamics and calorimetric analyses
- Plant responses to water stress
- Cancer-related Molecular Pathways
- Neuroscience and Neuropharmacology Research
- Epigenetics and DNA Methylation
- Medical and Biological Sciences
- Breast Implant and Reconstruction
- PARP inhibition in cancer therapy
- Parkinson's Disease Mechanisms and Treatments
- Cardiac pacing and defibrillation studies
- Connexins and lens biology
- Adenosine and Purinergic Signaling
University of Copenhagen
1995-2022
Danish Cancer Society
2006-2020
University of Michigan
2012
UiT The Arctic University of Norway
2012
Washtenaw Community College
2012
HUN-REN Szegedi Biológiai Kutatóközpont
1999
San Raffaele University of Rome
1998
Bikur Cholim Hospital
1979
Lysosomal membrane permeabilization (LMP) contributes to tissue involution, degenerative diseases, and cancer therapy. Its investigation has, however, been hindered by the lack of sensitive methods. Here, we characterize validate detection galectin puncta at leaky lysosomes as a highly easily manageable assay for LMP. LGALS1/galectin-1 LGALS3/galectin-3 are best suited this purpose due their widespread expression, rapid translocation availability high-affinity antibodies. Galectin staining...
Abstract Acquired resistance to classic caspase-mediated apoptosis is a common problem for the treatment of human cancer. Here, we show that siramesine, novel σ-2 receptor ligand, effectively induces caspase-independent programmed cell death in immortalized and transformed cells various origins. Siramesine-treated tumor displayed increased levels reactive oxygen species, lysosomal membrane permeabilization, chromatin condensation, shrinkage detachment cells. Lipid antioxidants (α-tocopherol...
AbstractA σ-2 receptor ligand siramesine induces lysosomal leakage and cathepsin-dependent death of cancer cells in vitro displays potent anti-cancer activity vivo. The mechanism by which destabilizes lysosomes is, however, unknown. Here, we show that a rapid rise the pH is followed dysfunction. accumulation into cell lysosomes, its ability to destabilize isolated chemical structure as an amphiphilic amine indicate it lysosomotropic detergent. Notably, triggers also substantial Atg6-...
Autophagy is one of the major intracellular catabolic pathways, but little known about composition autophagosomes. To study associated proteins, we isolated autophagosomes from human breast cancer cells using two different biochemical methods and three stimulus types: amino acid deprivation or rapamycin concanamycin A treatment. The autophagosome-associated proteins were dependent on stimulus, a core set was stimulus-independent. Remarkably, proteasomal abundant among stimulus-independent...
A central step in the transcriptional activation of heat shock genes Is binding factor (HSF) to upstream elements (HSEs). In vertebrates, HSF1 mediates ubiquitous response stress stimuli, while role a second HSE-bind-ing factor, HSF2, is still unclear. this work we show that both factors are expressed wide range murine tissues and each exists as two splicing isoforms. Although HSFs virtually proteins, their abundance predominant testls variable among other tissues, indicating specific...
Sphingomyelin is an essential cellular lipid that traffics between plasma membrane and intracellular organelles until directed to lysosomes for SMPD1 (sphingomyelin phosphodiesterase 1)-mediated degradation. Inactivating mutations in the gene result Niemann-Pick diseases type A B characterized by sphingomyelin accumulation severely disturbed tissue homeostasis. Here, we report overload disturbs maturation closure of autophagic membranes. patient fibroblasts SMPD1-depleted cancer cells...
The apoptosome, a heptameric complex of Apaf-1, cytochrome c, and caspase-9, has been considered indispensable for the activation caspase-9 during apoptosis. By using large panel genetically modified murine embryonic fibroblasts, we show here that, in response to tumor necrosis factor (TNF), caspase-8 cleaves activates an apoptosome-independent manner. Interestingly, caspase-8-cleaved induced lysosomal membrane permeabilization but failed activate effector caspases whereas...
Macroautophagy (hereafter referred to as autophagy) has recently emerged an attractive target for the treatment of various degenerative diseases and cancer. The discovery effective pharmaceutical regulators autophagy has, however, been hindered by a lack feasible assay systems autophagic flux. Here, we present luciferase-based reporter that measures flux in real time living cells demonstrate this system is apt detection dose- stimulus-dependent differences kinetics. Furthermore, screening...
Macroautophagy is a catabolic process that maintains cellular homeostasis and protects cells against various external stresses including starvation. Except for the identification of Akt-mTORC1 pathway as major negative regulator, little known about signaling networks control macroautophagy under optimal growth conditions. Therefore, we screened human kinome siRNA library siRNAs increase number autophagosomes in normally growing MCF-7 breast carcinoma cells, identified 10 kinases regulators...
Macroautophagy/autophagy is a central component of the cytoprotective cellular stress response. To enlighten stress-induced autophagy signaling, we screened human kinome siRNA library for regulators autophagic flux in MCF7 breast carcinoma cells and identified catalytic subunit DNA-dependent protein kinase PRKDC/DNA-PKcs as positive regulator basal DNA damage-induced autophagy. Analysis autophagy-regulating signaling cascades placed PRKDC upstream AMP-dependent (AMPK) complex ULK1 kinase. In...
The pathway leading to transcriptional activation of heat shock genes involves a step factor 1 (HSF1) trimerization required for high-affinity binding this activator protein elements (HSEs) in the promoters. Previous studies have shown that vivo is negatively regulated at physiological temperatures by mechanism requires multiple hydrophobic heptad repeats (HRs) which may form coiled coil monomer. To investigate minimal requirements negative regulation, work we examined mouse HSF1 translated...
The epidermis, outermost layer of the skin, forms a barrier and is involved in innate adaptive immunity an organism. Keratinocytes participate all these three protective processes. However, regulator keratinocyte responses against external dangers stresses remains elusive. We found that upregulation orphan gene 2610528A11Rik was common factor skin mice with several types inflammation. In human peptide expression G protein-coupled receptor 15 ligand (GPR15L), encoded by ortholog C10orf99 ,...
Abstract We report here on two female patients who had permanent pacemakers implanted in their chests and developed carcinoma of the breast subsequently. An association is suspected between cancer pacemaker, which an area borders with mammary gland or even right within it. This suspicion led us lately to change site subcutaneous pocket for implantation pacemaker a position higher chest than before. Moreover, we advocate frequent examinations all pacemakers.