Cardioprotection by Mitochondrial KATP Channel in Both Early and Late Preconditioning

2003 ◽  
pp. 189-204
Author(s):  
Yigang Wang ◽  
Meifeng Xu ◽  
Mitsuhiro Kudo ◽  
Ahmar Ayub ◽  
Muhammad Ashraf
Keyword(s):  
Katp Channel ◽  
Mitochondrial Katp Channel ◽  
Late Preconditioning

Selective mitochondrial KATP channel opening controls human myocardial preconditioning: Too much of a good thing?

Surgery ◽  
2000 ◽  
Vol 128 (2) ◽  
pp. 368-373 ◽  
Author(s):  
Benjamin J. Pomerantz ◽  
Thomas N. Robinson ◽  
Julie K. Heimbach ◽  
Casey M. Calkins ◽  
Stephanie A. Miller ◽  
...  
Keyword(s):  
Katp Channel ◽  
Good Thing ◽  
Mitochondrial Katp Channel ◽  
Myocardial Preconditioning ◽  
Channel Opening

Donor heart preservation with pinacidil: the role of the mitochondrial KATP channel

2004 ◽  
Vol 78 (2) ◽  
pp. 620-627 ◽  
Author(s):  
Michael D Diodato ◽  
Nirav R Shah ◽  
Sunil M Prasad ◽  
Sydney L Gaynor ◽  
Jennifer S Lawton ◽  
...  
Keyword(s):  
Katp Channel ◽  
Donor Heart ◽  
Mitochondrial Katp Channel ◽  
Heart Preservation

Opening of the mitochondrial KATP channel decreases JNK activity in the anoxic-reoxygenated embryonic heart

2007 ◽  
Vol 42 (6) ◽  
pp. S53-S54
Author(s):  
Alexandre Sarre ◽  
Stéphany Gardier ◽  
Fabienne Maurer ◽  
Christophe Bonny ◽  
Eric Raddatz
Keyword(s):  
Katp Channel ◽  
Embryonic Heart ◽  
Mitochondrial Katp Channel

ROS and NO trigger early preconditioning: relationship to mitochondrial KATP channel

2003 ◽  
Vol 284 (1) ◽  
pp. H299-H308 ◽  
Author(s):  
Gilles Lebuffe ◽  
Paul T. Schumacker ◽  
Zuo-Hui Shao ◽  
Travis Anderson ◽  
Hirotoro Iwase ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Reactive Oxygen Species ◽  
Methyl Ester ◽  
Katp Channel ◽  
Channel Blocker ◽  
No Synthase ◽  
Oxygen Species ◽  
Channel Activation ◽  
Mitochondrial Katp Channel ◽  
The Relationship

Reactive oxygen species (ROS) and nitric oxide (NO) are implicated in induction of ischemic preconditioning. However, the relationship between these oxidant signals and opening of the mitochondrial ATP-dependent potassium (KATP) channel during early preconditioning is not fully understood. We observed preconditioning protection by hypoxia, exogenous H2O2, or PKC activator PMA in cardiomyocytes subjected to 1-h ischemia and 3-h reperfusion. Protection was abolished by KATP channel blocker 5-hydroxydecanoate (5-HD) in each case, indicating that these triggers must act upstream from the KATP channel. Inhibitors of NO synthase abolished protection in preconditioned cells, suggesting that NO is also required for protection. DAF-2 fluorescence (NO sensitive) increased during hypoxic triggering. This was amplified by pinacidil and inhibited by 5-HD, indicating that NO is generated subsequent to KATP channel activation. Exogenous NO during the triggering phase conferred protection blocked by 5-HD. Exogenous NO also restored protection abolished by 5-HD or N ω-nitro-l-arginine methyl ester in preconditioned cells. Antioxidants given during pinacidil or NO triggering abolished protection, confirming that ROS are generated by KATP channel activation. Coadministration of H2O2 and NO restored PMA-induced protection in 5-HD-treated cells, indicating that ROS and NO are required downstream from the KATP channel. We conclude that ROS can trigger preconditioning by causing activation of the KATP channel, which then induces generation of ROS and NO that are both required for preconditioning protection.

scholarly journals The Opening of ATP-Sensitive K+ Channels Protects H9c2 Cardiac Cells Against the High Glucose-Induced Injury and Inflammation by Inhibiting the ROS-TLR4-Necroptosis Pathway

2017 ◽  
Vol 41 (3) ◽  
pp. 1020-1034 ◽  
Author(s):  
Weijie Liang ◽  
Meiji Chen ◽  
Dongdan Zheng ◽  
Jianhao Li ◽  
Mingcai Song ◽  
...  
Keyword(s):  
Cell Viability ◽  
Inflammatory Cytokines ◽  
High Glucose ◽  
Katp Channel ◽  
Channel Blocker ◽  
Cardiac Injury ◽  
Cardiac Cells ◽  
Mitochondrial Katp Channel ◽  
Channel Opening ◽  
Pre Treatment

Background/Aims: Hyperglycemia activates multiple signaling molecules, including reactive oxygen species (ROS), toll-like receptor 4 (TLR4), receptor-interacting protein 3 (RIP3, a kinase promoting necroptosis), which mediate hyperglycemia-induced cardiac injury. This study explored whether inhibition of ROS-TLR4-necroptosis pathway contributed to the protection of ATP-sensitive K+ (KATP) channel opening against high glucose-induced cardiac injury and inflammation. Methods: H9c2 cardiac cells were treated with 35 mM glucose (HG) to establish a model of HG-induced insults. The expression of RIP3 and TLR4 were tested by western blot. Generation of ROS, cell viability, mitochondrial membrane potential (MMP) and secretion of inflammatory cytokines were measured as injury indexes. Results: HG increased the expression of TLR4 and RIP3. Necrostatin-1 (Nec-1, an inhibitor of necroptosis) or TAK-242 (an inhibitor of TLR4) co-treatment attenuated HG-induced up-regulation of RIP3. Diazoxide (DZ, a mitochondrial KATP channel opener) or pinacidil (Pin, a non-selective KATP channel opener) or N-acetyl-L-cysteine (NAC, a ROS scavenger) pre-treatment blocked the up-regulation of TLR4 and RIP3. Furthermore, pre-treatment with DZ or Pin or NAC, or co-treatment with TAK-242 or Nec-1 attenuated HG-induced a decrease in cell viability, and increases in ROS generation, MMP loss and inflammatory cytokines secretion. However, 5-hydroxy decanoic acid (5-HD, a mitochondrial KATP channel blocker) or glibenclamide (Gli, a non-selective KATP channel blocker) pre-treatment did not aggravate HG-induced injury and inflammation. Conclusion: KATP channel opening protects H9c2 cells against HG-induced injury and inflammation by inhibiting ROS-TLR4-necroptosis pathway.

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