Author(s):
Soares, S. S. 
; Henao, Fernando ; Aureliano, M. ; Gutiérrez-Merino, Carlos
Date: 2008
Persistent ID: http://hdl.handle.net/10400.1/1356
Origin: Sapientia - Universidade do Algarve
Subject(s): Cell death; Vanadate
Description
Besides the well-known inotropic effects of vanadium in cardiac muscle, previous studies have shown that vanadate can stimulate cell growth or induce cell death. In this work, we studied the toxicity to neonatal rat ventricular myocytes (cardiomyocytes) of two vanadate solutions containing different
oligovanadates distribution, decavanadate (containing decameric vanadate, V10) and metavanadate (containing monomeric vanadate and also di-, tetra-, and pentavanadate). Incubation for 24 h with decavanadate or metavanadate induced necrotic cell death of cardiomyocytes, without significant caspase-3
activation. Only 10 μM total vanadium of either decavanadate (1 μMV10) or metavanadate (10 μM total vanadium) was needed to produce 50% loss of cell viability after 24 h (assessed with MTT and propidium
iodide assays). Atomic absorption spectroscopy showed that vanadium accumulation in cardiomyocytes
after 24 h was the same when incubation was done with decavanadate or metavanadate. A decrease of 75% of the rate of mitochondrial superoxide anion generation, monitored with dihydroethidium, and a sustained rise of cytosolic calcium (monitored with Fura-2-loaded cardiomyocytes) was observed after
24 h of incubation of cardiomyocytes with decavanadate or metavanadate concentrations close to those inducing 50% loss of cell viability produced. In addition, mitochondrial membrane depolarization within
cardiomyocytes, monitored with tetramethylrhodamine ethyl esther or with 3,3′,6,6′-tetrachloro-1,1′,3,3′-
tetraethylbenzimidazolcarbocyanine iodide, were observed after only 6 h of incubation with decavanadate
or metavanadate. The concentration needed for 50% mitochondrial depolarization was 6.5 ( 1 μM total
vanadium for both decavanadate (0.65 μMV10) and metavanadate. In conclusion, mitochondrial membrane
depolarization was an early event in decavanadate- and monovanadate-induced necrotic cell death of
cardiomyocytes.
