Kaczara, P;
Proniewski, B;
Lovejoy, C;
Kuś, K;
Motterlini, R;
Abramov, AY;
Chlopicki, S;
(2018)
CORM-401 induces calcium signalling, NO increase and activation of pentose phosphate pathway in endothelial cells.
The FEBS Journal
, 285
(7)
pp. 1346-1358.
10.1111/febs.14411.
Preview |
Text
febs14411.pdf - Accepted Version Download (1MB) | Preview |
Abstract
Carbon monoxide-releasing molecules (CO-RMs) induce nitric oxide (NO) release (which requires NADPH), and Ca2+-dependent signalling; however, their contribution in mediating endothelial responses is not clear. Here, we studied the effects of CO liberated from CORM-401 on NO production, calcium signalling and pentose phosphate pathway (PPP) activity in human endothelial cell line (EA.hy926). CORM-401 induced NO production and two types of calcium signalling: a peak-like calcium signal and a gradual increase in cytosolic calcium. CORM-401-induced peak-like calcium signal, originating from endoplasmic reticulum, was reduced by thapsigargin, a SERCA inhibitor, and by dantrolene, a ryanodine receptors (RyR) inhibitor. In contrast, the phospholipase C (PLC) inhibitor U73122 did not significantly affect peak-like calcium signalling, but a slow and progressive CORM-401-induced increase in cytosolic calcium was dependent on store-operated calcium entrance. CORM-401 augmented coupling of endoplasmic reticulum and plasmalemmal store-operated calcium channels (SOC). Interestingly, in the presence of NO synthase inhibitor (L-NAME) CORM-401-induced increases in NO and cytosolic calcium were both abrogated. CORM-401-induced calcium signalling was also inhibited by superoxide dismutase (PEG-SOD). Furthermore, CORM-401 accelerated PPP, increased NADPH concentration and decreased the ratio of reduced to oxidized glutathione (GSH/GSSG). Importantly, CORM-401-induced NO increase was inhibited by the PPP inhibitor 6-aminonicotinamide (6-AN), but neither by dantrolene nor by an inhibitor of large-conductance calcium-regulated potassium ion channel (paxilline). The results identify the primary role of CO-induced NO increase in the regulation of endothelial calcium signalling, that may have important consequences in controlling endothelial function. This article is protected by copyright. All rights reserved.
Archive Staff Only
 |
View Item |
