Calcium signals between the ryanodine receptor- and mitochondria critically regulate the effects of arsenite on mitochondrial superoxide formation and on the ensuing survival vs apoptotic signaling

Autor: Andrea Guidarelli, Orazio Cantoni, Liana Cerioni, Mara Fiorani
Jazyk: angličtina
Rok vydání: 2019
Předmět:
0301 basic medicine
Arsenite
Inositol-1
4
5-triphosphate receptor
Mitochondrial Ca(2+)
Mitochondrial superoxide
Ryanodine receptor
Survival vs apoptotic signaling
Clinical Biochemistry
7-chloro-5–2-chlorophenyl-1
5-dihydro-4
1-benzothiazepin-23H-one
CGP-37157
mitoO2-
mitochondrial superoxide
Apoptosis
Mitochondrion
Biochemistry
chemistry.chemical_compound
0302 clinical medicine
Superoxides
5-triphosphate receptor
CsA
cyclosporin A
IP3R
inositol 1
4
5-trisphosphate receptor
Cardiolipin
GSH
glutathione
D-cells
differentiated cells
MCU
mitochondrial Ca2+ uniporter
lcsh:QH301-705.5
Membrane Potential
Mitochondrial
lcsh:R5-920
Chemistry
Cell biology
Mitochondria
Nrf2
nuclear factor erythroid 2 p45-related factor 2
RP-cells
respiration-proficient cells
lcsh:Medicine (General)
Research Paper
Signal Transduction
Arsenites
Cell Survival
[Ca2+]c
cytosolic Ca2+ concentration
MPT
mitochondrial permeability transition
mNCX
mitochondrial Na+/Ca2+ exchanger
Cell Line
03 medical and health sciences
2-APB
2-aminoethoxydiphenyl borate
ROS
reactive oxygen species
NAO
10-N-nonyl acridine orange
Humans
Calcium Signaling
DNA Breaks
Single-Stranded
Uniporter
Ry
ryanodine
RR
ruthenium red
Mitochondrial transport
Organic Chemistry
Ryanodine Receptor Calcium Release Channel
Mitochondrial Ca2+
RyR
ryanodine receptor
Cf
caffeine
Cytosol
030104 developmental biology
Mitochondrial permeability transition pore
lcsh:Biology (General)
[Ca2+]m
mitochondrial Ca2+ concentration
RD-cells
respiration-deficient cells
AA
ascorbic acid
Inositol-1
Calcium
DHR
dihydrorhodamine 123
030217 neurology & neurosurgery
Biomarkers
Zdroj: Redox Biology, Vol 20, Iss, Pp 285-295 (2019)
Redox Biology
ISSN: 2213-2317
Popis: A low concentration of arsenite (6 h), selectively stimulating the intraluminal crosstalk between the inositol-1, 4, 5-triphosphate receptor and the ryanodine receptor (RyR), increased the mitochondrial transport of RyR-derived Ca2+ through the mitochondrial Ca2+ uniporter. This event was characterized in intact and permeabilized cells, and was shown to be critical for mitochondrial superoxide (mitoO2.-) formation. Inhibition of mitochondrial Ca2+ accumulation therefore prevented the effects of arsenite, in both the mitochondrial (e.g., cardiolipin oxidation) and extramitochondrial (e.g., DNA single- strand breakage) compartments, and suppressed the Nrf2/GSH survival signaling. The effects of arsenite on Ca2+ homeostasis and mitoO2.- formation were reversible, as determined after an additional 10 h incubation in fresh culture medium and by measuring long-term viability. A 16 h continuous exposure to arsenite instead produced a sustained increase in the cytosolic and mitochondrial Ca2+ concentrations, a further increased mitoO2.- formation and mitochondrial permeability transition. These events, followed by delayed apoptosis (48 h), were sensitive to treatments/manipulations preventing mitochondrial Ca2+ accumulation. Interestingly, cells remained viable under conditions in which the deregulated Ca2+ homeostasis was not accompanied by mitoO2.-formation. In conclusion, we report that the fraction of Ca2+ taken up by the mitochondria in response to arsenite derives from the RyR. Mitochondrial Ca2+ appears critical for mitoO2.- formation and for the triggering of both the cytoprotective and apoptotic signaling. The effects of arsenite were reversible, whereas its prolonged exposure caused a sustained increase in mitochondrial Ca2+ and mitoO2.- formation, and the prevalence of the apoptotic vs survival signaling.
Graphical abstract fx1
Databáze: OpenAIRE
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