TY - JOUR
T1 - Calcium ionophore A23187 reveals calcium related cellular stress as "I-Bodies"
T2 - An old actor in a new role
AU - Verma, Amit
AU - Bhatt, Anant Narayan
AU - Farooque, Abdullah
AU - Khanna, Suchit
AU - Singh, Saurabh
AU - Dwarakanath, Bilikere S.
N1 - Funding Information:
This work was supported by grants ( INM 301, 311/1.4 ) funded by Defence Research and Development Organisation , Government of India. A.V. was supported with a fellowship from Indian Council of Medical Research . We acknowledge Dr. Sudhir Chandna for extending the fluorescence microscope facility, Dr Seema Gupta for useful discussions and Dr. R.P. Tripathi, Director INMAS for constant support and encouragement.
PY - 2011/12
Y1 - 2011/12
N2 - 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 Ca2+ rich intracellular sites formed during stress-induced release of intracellular Ca2+, 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.
AB - 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 Ca2+ rich intracellular sites formed during stress-induced release of intracellular Ca2+, 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.
KW - A23187
KW - Calcium
KW - Cancer biomarker
KW - Mitochondrial aggregation
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U2 - 10.1016/j.ceca.2011.08.007
DO - 10.1016/j.ceca.2011.08.007
M3 - Article
AN - SCOPUS:82855161339
SN - 0143-4160
VL - 50
SP - 510
EP - 522
JO - Cell Calcium
JF - Cell Calcium
IS - 6
ER -
