Inhibition of glycogen synthase kinase 3β protects liver against ischemia/reperfusion injury by activating 5′ adenosine monophosphate‐activated protein kinase‐mediated autophagy

2018 ◽  
Vol 49 (4) ◽  
pp. 462-472 ◽  
Author(s):  
Defu Kong ◽  
Xiangwei Hua ◽  
Tian Qin ◽  
Jianjun Zhang ◽  
Kang He ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Glycogen Synthase ◽  
Ischemia Reperfusion ◽  
Adenosine Monophosphate ◽  
Glycogen Synthase Kinase ◽  
Glycogen Synthase Kinase 3Β

scholarly journals Effects of Glycogen Synthase Kinase‐beta Inhibition in Ischemia‐Reperfusion Injury of the Liver

2009 ◽  
Vol 23 (S1) ◽  
Author(s):  
Bruno Miguel Sepodes ◽  
João Pedro Rocha ◽  
Maria Eduardo‐Figueira ◽  
Christoph Thiemermann ◽  
Helder Mota‐Filipe
Keyword(s):  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Glycogen Synthase ◽  
Ischemia Reperfusion ◽  
Glycogen Synthase Kinase

scholarly journals Aldose reductase modulates cardiac glycogen synthase kinase-3β phosphorylation during ischemia-reperfusion

2012 ◽  
Vol 303 (3) ◽  
pp. H297-H308 ◽  
Author(s):  
Mariane Abdillahi ◽  
Radha Ananthakrishnan ◽  
Srinivasan Vedantham ◽  
Linshan Shang ◽  
Zhengbin Zhu ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Aldose Reductase ◽  
Glycogen Synthase ◽  
Ischemia Reperfusion ◽  
Left Ventricular ◽  
Cardiac Cells ◽  
Glycogen Synthase Kinase ◽  
Glycogen Synthase Kinase 3Β ◽  
Apoptotic Markers ◽  
Ldh Release

Earlier studies have demonstrated that aldose reductase (AR) plays a key role in mediating ischemia-reperfusion (I/R) injury. Our objective was to investigate if AR mediates I/R injury by influencing phosphorylation of glycogen synthase kinase-3β (p-GSK3β). To investigate this issue, we used three separate models to study the effects of stress injury on the heart. Hearts isolated from wild-type (WT), human expressing AR transgenic (ARTg), and AR knockout (ARKO) mice were perfused with/without GSK3β inhibitors (SB-216763 and LiCl) and subjected to I/R. Ad-human AR (Ad-hAR)-expressing HL-1 cardiac cells were exposed to hypoxia (0.5% O2) and reoxygenation (20.9% O2) conditions. I/R in a murine model of transient occlusion and reperfusion of the left anterior descending coronary artery (LAD) was used to study if p-GSK3β was affected through increased AR flux. Lactate dehydrogenase (LDH) release and left ventricular developed pressure (LVDP) were measured. LVDP was decreased in hearts from ARTg mice compared with WT and ARKO after I/R, whereas LDH release and apoptotic markers were increased ( P < 0.05). p-GSK3β was decreased in ARTg hearts compared with WT and ARKO ( P < 0.05). In ARKO, p-GSK3β and apoptotic markers were decreased compared with WT ( P < 0.05). WT and ARTg hearts perfused with GSK3β inhibitors improved p-GSK3β expression and LVDP and exhibited decreased LDH release, apoptosis, and mitochondrial pore opening ( P < 0.05). Ad-hAR-expressing HL-1 cardiac cells, exposed to hypoxia (0.5% O2) and reoxygenation (20.9% O2), had greater LDH release compared with control HL-1 cells ( P < 0.05). p-GSK3β was decreased and correlated with increased apoptotic markers in Ad-hAR HL-1 cells ( P < 0.05). Treatment with phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) inhibitor increased injury demonstrated by increased LDH release in ARTg, WT, and ARKO hearts and in Ad-hAR-expressing HL-1 cells. Cells treated with protein kinase C (PKC) α/β inhibitor displayed significant increases in p-Akt and p-GSK3β expression, and resulted in decreased LDH release. In summary, AR mediates changes in p-GSK3β, in part, via PKCα/β and Akt during I/R.

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