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
| Autor: | Meiji Chen, Jun Lan, Jianhao Li, Weijie Liang, Dongdan Zheng, Mingcai Song, Jianqiang Feng, Wenzhu Zhang |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Indoles Potassium Channels Physiology Apoptosis lcsh:Physiology Glyburide Myocytes Cardiac lcsh:QD415-436 Receptor K channels chemistry.chemical_classification Membrane Potential Mitochondrial Sulfonamides lcsh:QP1-981 Pinacidil Imidazoles Cell biology Biochemistry Receptor-Interacting Protein Serine-Threonine Kinases High glucose Necroptosis medicine.symptom Signal Transduction Cell signaling ATP-sensitive K+ channel Inflammation Biology H9c2 cardiac cells Cell Line lcsh:Biochemistry 03 medical and health sciences Necrosis medicine Animals Reactive oxygen species Diazoxide Toll-like receptor 4 Acetylcysteine Rats Oxidative Stress 030104 developmental biology Glucose chemistry Gene Expression Regulation TLR4 Hydroxy Acids Decanoic Acids |
| Zdroj: | Cellular Physiology and Biochemistry, Vol 41, Iss 3, Pp 1020-1034 (2017) |
| ISSN: | 1421-9778 1015-8987 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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