title: Calcium ionophore A23187 reveals calcium related cellular stress as "I-Bodies": an old actor in a new role.
abstract: Calcimycin (A23187) is an ionophore widely used in studies related to calcium dynamics in cells, but its fluorometric potential to reveal intracellular physiology has not been explored. Exploiting the microenvironment-induced changes in its fluorescence, we show that a brief exposure of cells to non-toxic concentrations (≤3μM) of the ionophore results in the characteristic organization of the ionophore forming brightly fluorescent cytoplasmic bodies termed "I-Bodies", which are closely related to stress linked disturbances/changes in calcium homeostasis. "I-Bodies" appear to be Ca(2+) rich intracellular sites formed during stress-induced release of intracellular Ca(2+), causing dysfunction and aggregation of mitochondria, providing scaffold for high density packing of A23187. Formation of "I-Bodies" in cells exposed to ionizing radiation and certain anticancer drugs suggest their potential in revealing alterations in calcium signaling and mitochondrial function during (related to) macromolecular damage-induced cell death. The absence of "I-Bodies" in non-malignant cells and their varying numbers in malignant cells with 5 fold increase in fluorescence imply that they can be potential biomarkers of cancer. Thus, "I-Bodies" are novel indicators of endogenous and induced stress linked to disturbances in calcium homeostasis in cells, with a potential to serve as biomarker of cancer.
authors.affiliation: Metabolic and Cell Signaling Group, Division of Radiation Biosciences, Institute of Nuclear Medicine and Allied Sciences, Brig. S. K. Mazumdar Marg, Delhi, India.
authors.forename: Amit
authors.initials: A
authors.lastname: Verma
authors.forename: Anant Narayan
authors.initials: AN
authors.lastname: Bhatt
authors.forename: Abdullah
authors.initials: A
authors.lastname: Farooque
authors.forename: Suchit
authors.initials: S
authors.lastname: Khanna
authors.forename: Saurabh
authors.initials: S
authors.lastname: Singh
authors.forename: Bilikere S
authors.initials: BS
authors.lastname: Dwarakanath
mesh_terms: D000814:Aniline Compounds; D000818:Animals; D014408:Biomarkers, Tumor; D000001:Calcimycin / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D061207:Calcium Ionophores / Q000494:pharmacology*; D045744:Cell Line, Tumor; D003593:Cytoplasm / Q000378:metabolism; D005047:Etoposide / Q000494:pharmacology; D006706:Homeostasis; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D013312:Stress, Physiological; D014966:Xanthenes
chemical_list: D000814:Aniline Compounds; D014408:Biomarkers, Tumor; D061207:Calcium Ionophores; D014966:Xanthenes; C059715:Fluo-3; D000001:Calcimycin; D005047:Etoposide; D002118:Calcium