Projects per year
Abstract
Hydrogen peroxide (H2O2) is a mitochondrial-derived reactive oxygen species (ROS) that regulates vascular signalling transduction, vasocontraction and vasodilation. Although the physiological role of ROS in endothelial cells is acknowledged, the mechanisms underlying H2O2 regulation of signalling in native, fully-differentiated endothelial cells is unresolved. In the present study, the effects of H2O2 on Ca2+ signalling were investigated in the endothelium of intact rat mesenteric arteries. Spontaneous local Ca2+ signals and acetylcholine evoked Ca2+ increases were inhibited by H2O2. H2O2 inhibition of acetylcholine-evoked Ca2+ signals was reversed by catalase. H2O2 exerts its inhibition on the IP3 receptor as Ca2+ release evoked by photolysis of caged IP3 was supressed by H2O2. H2O2 suppression of IP3-evoked Ca2+ signalling may be mediated by mitochondria. H2O2 depolarized mitochondria membrane potential. Acetylcholine-evoked Ca2+ release was inhibited by depolarisation of the mitochondrial membrane potential by the uncoupler carbonyl cyanide 3-chlorophenylhydrazone (CCCP) or complex 1 inhibitor, rotenone. We propose that the suppression of IP3-evoked Ca2+ release by H2O2 arises from the decrease in mitochondrial membrane potential. These results suggest that mitochondria may protect themselves against Ca2+ overload during IP3-linked Ca2+ signals by a H2O2 mediated negative feedback depolarization of the organelle and inhibition of IP3-evoked Ca2+ release.
Original language | English |
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Article number | 102108 |
Number of pages | 12 |
Journal | Cell Calcium |
Volume | 84 |
Early online date | 1 Nov 2019 |
DOIs | |
Publication status | Published - 31 Dec 2019 |
Keywords
- vascular
- endothelium
- calcium
- hydrogen peroxide
- free radical
- inositol 1,4,5-trisphosphate
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Dive into the research topics of 'Hydrogen peroxide depolarizes mitochondria and inhibits IP3-evoked Ca2+ release in the endothelium of intact arteries'. Together they form a unique fingerprint.Projects
- 4 Finished
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Optical dissection of endothelial calcium signalling Sir Henry Wellcome Postdoctoral Fellowship
Wilson, C. (Fellow)
17/04/17 → 16/10/21
Project: Research Fellowship
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Optical Cannula: Development of a tool for studying the inside of tubular organs under physiologically relevant conditions by imaging from within
McCarron, J. (Principal Investigator)
1/04/17 → 18/05/21
Project: Research
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ENDOTHELIAL Ca2+ SIGNALLING IN HYPERTENSION VISUALIZED FROM INSIDE PRESSURIZED ARTERIES
McCarron, J. (Principal Investigator) & Wilson, C. (Co-investigator)
1/02/17 → 3/09/21
Project: Research