Expression of the voltage-gated sodium channel NaV1.5 in the macrophage late endosome regulates endosomal acidification.
AuthorsCarrithers MD, Dib-Hajj S, Carrithers LM, Tokmoulina G, Pypaert M, Jonas EA, Waxman SG,
JournalJ Immunol
PubMed ID17548620
'Voltage-gated sodium channels expressed on the plasma membrane activate rapidly in response to changes in membrane potential in cells with excitable membranes such as muscle and neurons. Macrophages also require rapid signaling mechanisms as the first line of defense against invasion by microorganisms. In this study, our goal was to ... More
Fluorescence lifetime characterization of novel low-pH probes.
AuthorsLin HJ, Herman P, Kang JS, Lakowicz JR
JournalAnal Biochem
PubMed ID11444806
'The structures and functions of the cellular acidic compartments are strongly dependent on the pH gradients across vesicular membranes. Measurement and imaging of the vesicular pH require fluorophores with appropriate pK(a) values. In this report, we characterized the pH-dependent lifetime responses of a family of acidotropic probes, LysoSensors, to evaluate ... More
Expression and localization of cathepsin k in adult rat sertoli cells.
AuthorsAnway MD, Wright WW, Zirkin BR, Korah N, Mort JS, Hermo L
JournalBiol Reprod
PubMed ID14585819
'The cathepsins are a family of cysteine proteases that have been broadly implicated in proteolytic processes during cell growth, cell development, and normal adult cellular function. Cathepsin L is a major secretory product of rat and mouse Sertoli cells, the absence of which in furless mice is associated with atrophy ... More
Fluorescent indicators for intracellular pH.
AuthorsHan J, Burgess K,
JournalChem Rev
PubMed ID19831417
This review is about intracellular pH sensors, includingsmall fluorescent organic molecules, nanoparticles, andfluorescent proteins, e.g., GFP. It focuses on their preparations, photophysical properties, and advantages/disadvantagesfor intracellular pH measurements. The discussion is limitedto fluorescent indicators that have been applied to measureintracellular pH values since 1980. ... More
Tamoxifen inhibits acidification in cells independent of the estrogen receptor.
AuthorsAltan N, Chen Y, Schindler M, Simon SM
JournalProc Natl Acad Sci U S A
PubMed ID10200279
Tamoxifen has been reported to have numerous physiological effects that are independent of the estrogen receptor, including sensitization of resistant tumor cells to many chemotherapeutic agents. Drug-resistant cells sequester weak base chemotherapeutics in acidic organelles away from their sites of action in the cytosol and nucleus. This work reports that ... More
The p75 neurotrophin receptor can induce autophagy and death of cerebellar Purkinje neurons.
AuthorsFlorez-McClure ML, Linseman DA, Chu CT, Barker PA, Bouchard RJ, Le SS, Laessig TA, Heidenreich KA
JournalJ Neurosci
PubMed ID15140920
The cellular mechanisms underlying Purkinje neuron death in various neurodegenerative disorders of the cerebellum are poorly understood. Here we investigate an in vitro model of cerebellar neuronal death. We report that cerebellar Purkinje neurons, deprived of trophic factors, die by a form of programmed cell death distinct from the apoptotic ... More
Defective acidification in human breast tumor cells and implications for chemotherapy.
AuthorsAltan N, Chen Y, Schindler M, Simon SM
JournalJ Exp Med
PubMed ID9584137
Multidrug resistance (MDR) is a significant problem in the treatment of cancer. Chemotherapeutic drugs distribute through the cyto- and nucleoplasm of drug-sensitive cells but are excluded from the nucleus in drug-resistant cells, concentrating in cytoplasmic organelles. Weak base chemotherapeutic drugs (e.g., anthracyclines and vinca alkaloids) should concentrate in acidic organelles. ... More
Kinetics of doxorubicin handling in the LLC-PK1 kidney epithelial cell line is mediated by both vesicle formation and P-glycoprotein drug transport.
AuthorsCrivellato E, Candussio L, Rosati AM, Decorti G, Klugmann FB, Mallardi F
JournalHistochem J
PubMed ID10576412
The subcellular distribution of doxorubicin was evaluated in living non-fixed LLC-PK1 cells, which maintain the structural and functional characteristics of the kidney proximal tubule epithelium and also express P-glycoprotein. After 10 min incubation, doxorubicin fluorescence was detectable in the nucleus. The intensity of nuclear fluorescence progressively increased, reaching the maximum ... More
The lipofuscin fluorophore A2E perturbs cholesterol metabolism in retinal pigment epithelial cells.
AuthorsLakkaraju A, Finnemann SC, Rodriguez-Boulan E
JournalProc Natl Acad Sci U S A
PubMed ID17578916
Proteins involved in cholesterol trafficking are known to contribute to the pathogenesis of atherosclerosis and Alzheimer's disease. Allelic variants in the cholesterol transporters apolipoprotein E and ATP-binding cassette protein A1 (ABCA1) have recently been associated with susceptibility to age-related macular degeneration (AMD). Histopathological analyses of eyes with AMD demonstrate the ... More
Identification of organelles in bacteria similar to acidocalcisomes of unicellular eukaryotes.
AuthorsSeufferheld M, Vieira MC, Ruiz FA, Rodrigues CO, Moreno SN, Docampo R
JournalJ Biol Chem
PubMed ID12783865
Acidocalcisomes are acidic calcium storage compartments described in several unicellular eukaryotes, including trypanosomatid and apicomplexan parasites, algae, and slime molds. In this work, we report that the volutin granules of Agrobacterium tumefaciens possess properties similar to the acidocalcisomes. Transmission electron microscopy revealed that each intracellular granule was surrounded by a ... More
RORα Enhances Lysosomal Acidification and Autophagic Flux in the Hepatocytes.
Authors
JournalHepatol Commun
PubMed ID34558854
Restoration of CTSD (cathepsin D) and lysosomal function in stroke is neuroprotective.
Authors
JournalAutophagy
PubMed ID32450052
Protective responses to sublytic complement in the retinal pigment epithelium.
Authors
JournalProc Natl Acad Sci U S A
PubMed ID27432952
Restraining Lysosomal Activity Preserves Hematopoietic Stem Cell Quiescence and Potency.
Authors
JournalCell Stem Cell
PubMed ID32109377
Melanoma-Secreted Lysosomes Trigger Monocyte-Derived Dendritic Cell Apoptosis and Limit Cancer Immunotherapy.