Sulodexide attenuates endoplasmic reticulum stress induced by myocardial ischaemia/reperfusion by activating the PI3K/Akt pathway

Shen, Danhong; Chen, Ruiyao; Zhang, Lijing; Rao, Zhiheng; Ruan, Yongxue; Li, Lei; Chu, Maoping; Zhang, Yuanhai

doi:10.1111/jcmm.14367

Cited by 37 publications

(41 citation statements)

References 37 publications

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“…A stainless-steel injection catheter was then inserted (0.64 mm outer diameter) vertically into the puncture site, and gel was used on the surface of the skull to close the skin. The PI3K inhibitor LY294002 (Sigma-Aldrich, St. Louis, MO, United States; Shen et al, 2019; Zhan et al, 2019) was dissolved in dimethylsulfoxide (DMSO) at a concentration of 0.3 mg/ml and intracranially injected at a dose of 0.3 mg/kg at the beginning of hypoperfusion. In the Sham group, the bilateral common carotid arteries were separated from the nerves but not ligated, and 1 ml of 25% DMSO was intragastrically administered daily.…”

Section: Methodsmentioning

confidence: 99%

Resveratrol Activates Autophagy via the AKT/mTOR Signaling Pathway to Improve Cognitive Dysfunction in Rats With Chronic Cerebral Hypoperfusion

Wang¹,

He²,

Pan³

et al. 2019

Front. Neurosci.

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Chronic cerebral hypoperfusion (CCH) is a main cause of vascular dementia and is also an etiological factor of neurological diseases and mental disorders. However, few treatments are available for CCH, and new medications are needed. In the present study, we employed a rat model of CCH that was based on bilateral common carotid artery occlusion and investigated the therapeutic effects of resveratrol and its detailed mechanism of action. We evaluated neurological deficit scores and performed the Morris water maze test, hematoxylin and eosin staining, TUNEL staining, enzyme-linked immunosorbent assays, and Western blot. Resveratrol reduced neurological deficit scores in CCH rats and reduced pathological damage in the frontal cortex and hippocampus. Resveratrol activated autophagy and inhibited the expression of AKT/mechanistic target of rapamycin (mTOR) signaling pathway-related proteins. Treatment with a phosphoinositide-3 kinase inhibitor reversed the protective effect of resveratrol. These findings suggest that resveratrol improves cognitive function in a rat model of CCH and reduces oxidative stress-induced neuronal damage in the frontal cortex and hippocampus by activating autophagy and inhibiting neuronal apoptosis. These effects may be regulated by the AKT/mTOR signaling pathway.

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Section: Methodsmentioning

confidence: 99%

Resveratrol Activates Autophagy via the AKT/mTOR Signaling Pathway to Improve Cognitive Dysfunction in Rats With Chronic Cerebral Hypoperfusion

Wang¹,

He²,

Pan³

et al. 2019

Front. Neurosci.

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“…Finally, in regards to apoptosis, the inhibition of ER stress in in vitro and in vivo myocardial I/R models reveals beneficial effects on cardiac injury, myocardial apoptosis, and infarct area. Inhibition of ER stress increases the expression of superoxide dismutase (SOD) and Bcl-2, which, consequently, decreases the expression of Bax, resulting in the inhibition of apoptosis [73].…”

Section: Alterations Of Interactions Between the Er And Mitochondria mentioning

confidence: 99%

“…Another option is the utilization of metformin, a traditional anti-diabetic drug, which decreases ER stress-induced cardiac injury through the protection of mitochondria and attenuation of CHOP expression during cardiac I/R [100]. Moreover, sulodexide (SDX), a glycosaminoglycan, decreases cardiac injury, infarct area, and myocardial apoptosis during I/R through increased Bcl-2 and decreased Bax expression in a mouse model of I/R, suggesting that SDX has in vivo a cardioprotective role in the suppression of ER stress and apoptosis [73]. In addition, ER-mitochondrial cross talk can be regulated by exogenous H2S, which inhibits the activation of apoptotic pathways [88].…”

Section: Pharmacological Interventions-improved Interactions Between mentioning

confidence: 99%

Imbalance of ER and Mitochondria Interactions: Prelude to Cardiac Ageing and Disease?

Jin

Zhang

Brundel

et al. 2019

Cells

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Cardiac disease is still the leading cause of morbidity and mortality worldwide, despite some exciting and innovative improvements in clinical management. In particular, atrial fibrillation (AF) and heart failure show a steep increase in incidence and healthcare costs due to the ageing population. Although research revealed novel insights in pathways driving cardiac disease, the exact underlying mechanisms have not been uncovered so far. Emerging evidence indicates that derailed proteostasis (i.e., the homeostasis of protein expression, function and clearance) is a central component driving cardiac disease. Within proteostasis derailment, key roles for endoplasmic reticulum (ER) and mitochondrial stress have been uncovered. Here, we describe the concept of ER and mitochondrial stress and the role of interactions between the ER and mitochondria, discuss how imbalance in the interactions fuels cardiac ageing and cardiac disease (including AF), and finally assess the potential of drugs directed at conserving the interaction as an innovative therapeutic target to improve cardiac function. of 15including the ubiquitin-proteasomal system (UPS) and autophagy [9]. In general, cellular stress, including stress caused by cardiac disease, activates multiple stress pathways, including the cytosolic heat shock response, the endoplasmic reticulum (ER) unfolded protein response (UPR ER ), and the mitochondrial UPR (UPR mt ) [10][11][12].Within the PQC, the ER and mitochondria play a critical role in the regulation of protein homeostasis and the maintenance of normal cellular function. The ER is an essential organelle involved in protein synthesis, folding, and trafficking. As protein folding is an error-prone process, the PQC system of the ER is specialized in optimizing this process, thereby preserving cardiac protein quality and homeostasis [13]. As approximately 30% of the cardiomyocyte volume is comprised of mitochondria, the maintenance of a healthy and functional mitochondrial PQC system, which includes molecular chaperones (e.g., HSP60 and HSP10) and proteases (e.g., ClpP), is critical to conserve the energy balance and cardiomyocyte function. The PQC system in mitochondria activates, upon stress, protein folding assistance mechanisms and promotes clearance of misfolded proteins to preserve mitochondrial function [14,15].Thus, a healthy proteostasis in cardiomyocytes safeguards the proper contractile function in the heart. The ER and mitochondria are essential organelles for regulating protein homeostasis, thereby guaranteeing cardiomyocyte function and survival. Therefore, a deeper understanding of ER and mitochondrial function during health and cardiac disease is required to ultimately develop novel therapeutic strategies. Role of the ER in Cardiac HealthThe ER is an essential organelle supporting multiple cellular processes such as protein synthesis, protein folding, regulation of Ca 2+ homeostasis, and contribution to the generation of autophagosomes and peroxisomes [16]. The ER lumen constitutes of a specialized fol...

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“…Serum stimulation was performed by switching the culture medium to 10% FBS after serum starvation. TBHP is an oxidant for I/R injury in various cultured cells, including renal epithelial cells (Paller and Manivel, 1992;Wu et al, 2017;Chen et al, 2018;Shen et al, 2019). In order to determine the effect of FGF2 on TBHP-induced ER stress, NRK-52E cells were divided into six groups randomly: (a) Vehicle group: NRK-52E cells were cultured in complete medium without any supplement; (b) FGF2 group: NRK-52E cells were cultured in complete medium and treated with recombinant human FGF2 (100 ng/ml) for 2 h; (c) TBHP group: NRK-52E cells were cultured in complete medium, and then TBHP (200 µmol/L) was added for an additional 12 h; (d) TBHP-FGF2 group: NRK-52E cells were pretreated with recombinant human FGF2 (100 ng/ml) for 2 h, and then TBHP (200 µmol/L) was added for an additional 12 h; (e) LY294002 group: NRK-52E cells were pretreated for 2 h with specific Akt pathway inhibitor LY294002 (20 µmol/L), and then cells were treated as in the TBHP + FGF2 group.…”

Section: Cell Culturementioning

confidence: 99%

Fibroblast Growth Factor 2 Attenuates Renal Ischemia-Reperfusion Injury via Inhibition of Endoplasmic Reticulum Stress

Tan

Tao

et al. 2020

Front. Cell Dev. Biol.

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Acute kidney injury (AKI) is a serious clinical disease that is mainly caused by renal ischemia-reperfusion (I/R) injury, sepsis, and nephrotoxic drugs. The pathologic mechanism of AKI is very complex and may involve oxidative stress, inflammatory response, autophagy, apoptosis, and endoplasmic reticulum (ER) stress. The basic fibroblast growth factor (FGF2) is a canonic member of the FGF family that plays a crucial role in various cellular processes, including organ development, wound healing, and tissue regeneration. However, few studies have reported the potential therapeutic effect of FGF2 in the repair of renal ischemic injury in the past two decades. In the present study, we investigated the protective effect of FGF2 on renal I/R injury using Sprague-Dawley and NRK-52E cells. Our results showed that FGF2 significantly attenuates the apoptosis of kidney tissues after I/R injury through the inhibition of excessive ER stress. Moreover, FGF2 also alleviated the excessive ER stress and apoptosis in cultured NRK-52E cells injured by tert-Butyl hydroperoxide (TBHP). Significantly, phosphatidylinositol 3-kinase (PI3K)-selective inhibitor LY294002 and mitogen-activated protein kinase kinase (MEK)-selective inhibitor U0126 were utilized in the present study to examine the protective mechanism of FGF2. Our in vitro experimental results confirmed that both LY294002 and U0126 largely abolished the protective effect of FGF2. Taken together, the findings of the present study indicated that FGF2 attenuates I/R-induced renal epithelial apoptosis by suppressing excessive ER stress via the activation of the PI3K/AKT and MEK-ERK1/2 signaling pathways.

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Sulodexide attenuates endoplasmic reticulum stress induced by myocardial ischaemia/reperfusion by activating the PI3K/Akt pathway

Cited by 37 publications

References 37 publications

Resveratrol Activates Autophagy via the AKT/mTOR Signaling Pathway to Improve Cognitive Dysfunction in Rats With Chronic Cerebral Hypoperfusion

Resveratrol Activates Autophagy via the AKT/mTOR Signaling Pathway to Improve Cognitive Dysfunction in Rats With Chronic Cerebral Hypoperfusion

Imbalance of ER and Mitochondria Interactions: Prelude to Cardiac Ageing and Disease?

Fibroblast Growth Factor 2 Attenuates Renal Ischemia-Reperfusion Injury via Inhibition of Endoplasmic Reticulum Stress

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