ArticlePloS one2012
Fasudil protects the heart against ischemia-reperfusion injury by attenuating endoplasmic reticulum stress and modulating SERCA activity: the differential role for PI3K/Akt and JAK2/STAT3 signaling pathways.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 75 citations in OpenAlex.
- Article
- Untangling the role of RhoA in the heart: protective effect and mechanism.Cell death & disease · 2024Review
- Article
- Quercetin ameliorates testosterone secretion disorder by inhibiting endoplasmic reticulum stress through the miR-1306-5p/HSD17B7 axis in diabetic rats.Bosnian journal of basic medical sciences · 2022Article
- Chemical Chaperones to Inhibit Endoplasmic Reticulum Stress: Implications in Diseases.Drug design, development and therapy · 2022Review
- Sevoflurane alleviates oxygen-glucose deprivation/reoxygenation-induced injury in HT22 cells through regulation of the PI3K/AKT/GSK3β signaling pathway.Experimental and therapeutic medicine · 2021Article
- Inhibition of Rho-kinase is involved in the therapeutic effects of atorvastatin in heart ischemia/reperfusion.Experimental and therapeutic medicine · 2020Article
- Inhibition of Rho-associated protein kinase improves the survival of human induced pluripotent stem cell-derived cardiomyocytes after dissociation.Experimental and therapeutic medicine · 2020Article
- Remote ischemic post-conditioning protects against myocardial ischemia/reperfusion injury by inhibiting the Rho-kinase signaling pathway.Experimental and therapeutic medicine · 2020Article
- Mechanism of HExperimental and therapeutic medicine · 2019Article
- l-α-Lysophosphatidylinositol (LPI) aggravates myocardial ischemia/reperfusion injury via a GPR55/ROCK-dependent pathway.Pharmacology research & perspectives · 2019Article
- An Update on the Multifaceted Roles of STAT3 in the Heart.Frontiers in cardiovascular medicine · 2019Review
- Enhanced anti-tumor effect of liposomal Fasudil on hepatocellular carcinoma in vitro and in vivo.PloS one · 2019Article
- Hydrogen-rich solution attenuates myocardial injury caused by cardiopulmonary bypass in rats via the Janus-activated kinase 2/signal transducer and activator of transcription 3 signaling pathway.Oncology letters · 2018Article
- Compound K Induces Endoplasmic Reticulum Stress and Apoptosis in Human Liver Cancer Cells by Regulating STAT3.Molecules (Basel, Switzerland) · 2018Article
- PPARα activation alleviates damage to the cytoskeleton during acute myocardial ischemia/reperfusion in rats.Molecular medicine reports · 2018Article
- Protective effects of N(2)‑L‑alanyl‑L‑glutamine mediated by the JAK2/STAT3 signaling pathway on myocardial ischemia reperfusion.Molecular medicine reports · 2018Article
- Rho kinase signaling and cardiac physiology.Current opinion in physiology · 2018Article
- Fasudil, a Rho-Kinase Inhibitor, Exerts Cardioprotective Function in Animal Models of Myocardial Ischemia/Reperfusion Injury: A Meta-Analysis and Review of Preclinical Evidence and Possible Mechanisms.Frontiers in pharmacology · 2018Article
- Activation of γ2-AMPK Suppresses Ribosome Biogenesis and Protects Against Myocardial Ischemia/Reperfusion Injury.Circulation research · 2017Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Disordered calcium homeostasis can lead to endoplasmic reticulum (ER) stress. Our previous data showed that time course activation of ER stress contributes to time-related increase in ischemia-reperfusion (I/R) injury. However, it has not been tested whether PI3K/Akt and JAK2/STAT3 pathways play differential roles in reducing ER stress to protect the heart. In the present study, using fasudil which is a specific inhibitor of ROCK, we aimed to investigate whether improved SERCA expression and activity accounts for reduced ER stress by ROCK inhibition, specifically whether PI3K/Akt and JAK2/STAT3 pathways are differentially involved in modulating SERCA activity to reduce ER stress and hence I/R injury. The results showed that during the reperfusion period following 45 min of coronary ligation the infarct size (IS) increased from 3 h of reperfusion (45.4±5.57%) to 24 h reperfusion (64.21±5.43, P<0.05), which was associated with ER stress dependent apoptosis signaling activation including CHOP, Caspase-12 and JNK (P<0.05, respectively).The dynamic ER stress activation was also related to impaired SERCA activity at 24 h of reperfusion. Administration of fasudil at 10 mg/Kg significantly attenuated ROCK activation during reperfusion and resulted in an improved SERCA activity which was closely associated with decreases in temporal activation of ER stress and IS changes. Interestingly, while both PI3K/Akt and JAK2/STAT3 signaling pathways played equal role in the protection offered by ROCK inhibition at 3 h of reperfusion, the rescued SERCA expression and activity at 24 h of reperfusion by fasudil was mainly due to JAK2/STAT3 activation, in which PI3K/Akt signaling shared much less roles.
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