Dysregulated calcium homeostasis and oxidative stress in chronic myeloid leukemia (CML) cells.
Chronic myeloid leukemia (CML) is a hematopoietic stem cell disorder caused by the oncogenic activity of the Bcr-Abl protein, a deregulated tyrosine kinase. Calcium may act directly on cellular enzymes and in conjunction with other cellular metabolites, such as cyclic nucleotides, to regulate cell functions. Alteration in the ionized calcium concentration in the cytosol has been implicated in the initiation of secretion, contraction, and cell proliferation as well as the production of reactive oxygen species (ROS) has been correlates with normal cell proliferation through activation of growth-related signaling pathways. In this study we evaluated in peripheral blood leukocytes from CML patients the role of the balance between intracellular calcium and oxidative stress in CML disease in order to identify possible therapeutic targets in patients affected by this pathology. Our results demonstrated that peripheral blood mononuclear cells derived from CML patients displayed decreased intracellular calcium [Ca(2+)](i) fluxes both after InsP(3) as well as ATP and ionomycin (IONO) administration. CML cells showed lower levels of superoxide dismutase (SOD) activity and significantly higher malondialdehyde levels (MDA) than peripheral blood mononuclear cells derived from control patients. Finally we showed that resveratrol is able to down-regulate InsP3 and ATP effects on intracellular calcium [Ca(2+)](i) fluxes as well as the effects of ATP and IONO on oxidative stress in CML cells.
Ciarcia
Roberto
R
Department of Structures, Functions and Biological Technologies, School of Veterinary Medicine, University of Naples Federico II, Naples, Italy.
d'Angelo
Danila
D
Pacilio
Carmen
C
Pagnini
David
D
Galdiero
Massimiliano
M
Fiorito
Filomena
F
Damiano
Sara
S
Mattioli
Eliseo
E
Lucchetti
Chiara
C
Florio
Salvatore
S
Giordano
Antonio
A
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000328:Adult; D002118:Calcium / Q000378:metabolism*; D005260:Female; D006706:Homeostasis / Q000187:drug effects; D006801:Humans; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D015759:Ionomycin / Q000494:pharmacology; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008875:Middle Aged; D009569:Nitric Oxide / Q000096:biosynthesis; D018384:Oxidative Stress / Q000187:drug effects; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000378:metabolism
D013267:Stilbenes; D009569:Nitric Oxide; D008315:Malondialdehyde; D015759:Ionomycin; D000255:Adenosine Triphosphate; D013482:Superoxide Dismutase; D000077185:Resveratrol; D002118:Calcium