ischemia and endoplasmic reticulum and autophagy

AIMS: Mitochondria-associated endoplasmic reticulum membranes (MAMs) serve as a crucial bridge connecting the endoplasmic reticulum (ER) and mitochondria within cells. Vesicle-associated membrane protein-associated protein B (VAPB) and protein tyrosine phosphatase interacting protein 51 (PTPIP51) are responsible for the formation and stability of MAMs, which have been implicated in the pathogenesis of various diseases. However, the role of MAMs in ischemic stroke (IS) remains unclear...

Many pathologic states can lead to the accumulation of unfolded/misfolded proteins in cells. This causes endoplasmic reticulum (ER) stress and triggers the unfolded protein response (UPR), which encompasses three main adaptive branches. One of these UPR branches is mediated by protein kinase RNA-like ER kinase (PERK), an ER stress sensor. The primary consequence of PERK activation is the suppression of global protein synthesis, which reduces ER workload and facilitates the recovery of ER function. Ischemic stroke induces ER stress and activates the UPR...

Tyrosine kinase inhibitors (TKIs) have been recognized as crucial agents for treating various tumors, and one of their key targets is the intracellular site of the vascular endothelial growth factor receptor (VEGFR). While TKIs have demonstrated their effectiveness in solid tumor patients and increased life expectancy, they can also lead to adverse cardiovascular effects including hypertension, thromboembolism, cardiac ischemia, and left ventricular dysfunction. Among the TKIs, sorafenib was the first approved agent and it exerts anti-tumor effects on hepatocellular carcinoma (HCC) and renal cell carcinoma (RCC) by inhibiting angiogenesis and tumor cell proliferation through targeting VEGFR and RAF...

Myocardial ischemia-reperfusion injury (MIRI) poses a significant threat to patients with coronary heart disease. Adenosine A2A receptors have been known as a protective role in MIRI by regulating autophagy, so we assumed that activation of adenosine A2B receptor (A2BAR) might exert a similar effect during MIRI and underlying mechanism be related to proteostasis maintenance as well. In situ hearts were subjected to 30 min of ischemia and 120 min of reperfusion (IR), while in vitro cardiomyocytes from neonatal rats experienced 6 h of oxygen-glucose deprivation followed by 12 h of reoxygenation (OGDR)...

BACKGROUND: Ischemia/reperfusion injury (IRI) can lead to acute kidney injury and result in high disability and mortality rates. Cystathionine γ-lyase (CSE)-produced hydrogen sulfide (H2 S) has been confirmed to play a protective role in renal IRI. While autophagy is involved in renal IRI, its role in the regulation by endoplasmic reticulum stress (ERS) has not been considered. Our study explored the role of CSE/H2 S in protecting against renal IRI by regulating ERS-induced autophagy...

Ischemia-reperfusion injury is an event concerning any organ under a procedure of transplantation. The early result of ischemia is hypoxia, which causes malfunction of mitochondria and decrease in cellular ATP. This leads to disruption of cellular metabolism. Reperfusion also results in cell damage due to reoxygenation and increased production of reactive oxygen species, and later by induced inflammation. In damaged and hypoxic cells, the endoplasmic reticulum (ER) stress pathway is activated by increased amount of damaged or misfolded proteins, accumulation of free fatty acids and other lipids due to inability of their oxidation (lipotoxicity)...

Calcium overload is the key trigger in cardiac microvascular ischemia-reperfusion (I/R) injury, and calreticulin (CRT) is a calcium buffering protein located in the endoplasmic reticulum (ER). Additionally, the role of pinacidil, an antihypertensive drug, in protecting cardiac microcirculation against I/R injury has not been investigated. Hence, this study aimed to explore the benefits of pinacidil on cardiac microvascular I/R injury with a focus on endothelial calcium homeostasis and CRT signaling. Cardiac vascular perfusion and no-reflow area were assessed using FITC-lectin perfusion assay and Thioflavin-S staining...

In recent years, the incidence of intestinal ischemia-reperfusion injury (II/RI), inflammatory bowel disease (IBD), and colorectal cancer (CRC) has been gradually increasing, posing significant threats to human health. Autophagy and endoplasmic reticulum stress (ERS) play important roles in II/RI. Damage caused by ischemia and cellular stress can activate ERS, which in turn initiates autophagy to clear damaged organelles and abnormal proteins, thereby alleviating ERS and maintaining the intestinal environment...

BACKGROUND: Cerebral ischemia-reperfusion injury (CIRI) is a complex pathophysiological process that typically occurs during the treatment of ischemia, with limited therapeutic options. Autophagy plays a vital role during the reperfusion phase and is a potential therapeutic target for preventing and treating cerebral ischemia-reperfusion injury. METHODS: We conducted a comprehensive search of the Web of Science Core Collection for publications related to cerebral ischemia-reperfusion injury with autophagy, published between January 1, 2008, and January 1, 2023...

Autophagy involves the sequestration and delivery of cytoplasmic materials to lysosomes, where proteins, lipids, and organelles are degraded and recycled. According to the way the cytoplasmic components are engulfed, autophagy can be divided into macroautophagy, microautophagy, and chaperone-mediated autophagy. Recently, many studies have found that autophagy plays an important role in neurological diseases, including Alzheimer's disease, Parkinson's disease, Huntington's disease, neuronal excitotoxicity, and cerebral ischemia...

This study aimed to determine whether endoplasmic reticulum (ER) stress is involved in impaired autophagy after myocardial ischemia/reperfusion I/R (M-I/R) and elucidate the underlying mechanisms. The expression levels of STING and IRF3 phosphorylation increased in M-I/R heart tissues and hypoxia/reoxygenation (H/R)-treated H9c2 cells. The ER stress inhibitor 4-phenylbutyric acid (4-PBA)significantly suppressed the stimulation of STING-IRF3 transcription and alleviatedcardiac dysfunction caused by M-I/R injury...

BACKGROUND: Neuroprotective effects have been the main focus of new treatment modalities for ischemic stroke. Phenothiazines, or chlorpromazine plus promethazine (C + P), are known to prevent the generation of free radicals and uptake of Ca2+ by plasma membrane; they have a potential as a treatment for acute ischemic stroke (AIS). This study aims to investigate the role of endoplasmic reticulum (ER) stress-associated PERK-eIF2α pathway underlying the phenothiazine-induced neuroprotective effects after cerebral ischemia/reperfusion (I/R) injury...

Botulinum toxin type A (BTXA) previously protected endothelial cells in free skin flaps from ischemia/reperfusion injury by inducing autophagy. Endoplasmic reticulum (ER) stress-autophagy activation may have a role in BTXA-antagonized ischemia/reperfusion damage in human dermal microvascular endothelial cells (HDMECs), however, this has yet to be proven. HDMECs were pretreated with BTXA at various concentrations for 12 h before being subjected to hypoxia and reoxygenation (H/R). Cell Count Kit 8 (CCK8) and Western blot (WB) data showed that H/R treatment significantly increased the expression of ER stress (GRP78, CHOP) and autophagy (LC3II/I, Beclin-1) proteins...

Hepatic ischemia-reperfusion injury (HIRI) usually occurs during subtotal hepatectomy and severely damages liver function during the perioperative period. Endoplasmic reticulum stress (ERS) dependent apoptosis has been suggested to play a crucial role in HIRI progression. The present study focused on the regulatory effect of autophagy activation induced by ischemic preconditioning (IPC) on ERS-dependent apoptosis of hepatocytes in HIRI. A HIRI mouse model and oxygen-glucose deprivation/reperfusion (OGD/R) AML-12 hepatocyte cell lines were constructed to evaluate the protective effect of IPC in vivo and in vitro...

Kidney damage due to ischemia or rejection results in the accumulation of unfolded and misfolded proteins in the endoplasmic reticulum (ER) lumen, a condition known as "ER stress." Inositol-requiring enzyme 1α (IRE1α), the first ER stress sensor found, is a type I transmembrane protein with kinase and endoribonuclease activity. On activation, IRE1α nonconventionally splices an intron from unspliced X-box-binding protein 1 (XBP1) mRNA to produce XBP1s mRNA that encodes the transcription factor, XBP1s, for the expression of genes encoding proteins that mediate the unfolded protein response...

Cerebral ischemia/reperfusion (I/R) injury can result in different levels of cerebral impairment, and in severe cases, death. Curcumin, an essential bioactive component of turmeric, has a rich history as a traditional medicine for various ailments in numerous countries. Experimental and clinical research has established that curcumin offers a protective effect against cerebral I/R injury. Curcumin exerts its protective effects by acting on specific mechanisms such as antioxidant, anti-inflammatory, inhibition of ferroptosis and pyroptosis, protection of mitochondrial function and structure, reduction of excessive autophagy, and improvement of endoplasmic reticulum (ER) stress, which ultimately help to preserve the blood-brain barrier (BBB) and reducing apoptosis...

BACKGROUND: The pathological basis for many retinal diseases, retinal ischemia is also one of the most common causes of visual impairment. Numerous ocular diseases have been linked to Endoplasmic reticulum(ER)stress. However, there is still no clear understanding of the relationship between ER stress and Müller glial cells during retinal ischemia and hypoxia. This study examined the effects of ER stress on autophagy and apoptosis-related proteins, as well as the microtubule-related protein tau in rMC-1 cells...

Ischemic stroke is a leading cause of disability worldwide. There is no simple treatment to alleviate ischemic brain injury, as thrombolytic therapy is applicable within a narrow time window. During the last years, the ketogenic diet (KD) and the exogenous administration of the ketone body β-hydroxybutyrate (BHB) have been proposed as therapeutic tools for acute neurological disorders and both can reduce ischemic brain injury. However, the mechanisms involved are not completely clear. We have previously shown that the D enantiomer of BHB stimulates the autophagic flux in cultured neurons exposed to glucose deprivation (GD) and in the brain of hypoglycemic rats...

OBJECTIVES: Ischemia-reperfusion injury is a complicated pathologic process that involves multiple factors including oxidative stress, endoplasmic reticulum stress, calcium overload, inflammatory response, disturbances in energy metabolism, apoptosis, and some newly-described forms of programmed cell death (e.g., necroptosis, autophagy, pyroptosis, patanatos, and ferroptosis). Chinese herbal monomers (CHMs) have long been applied to treat ischemia-reperfusion injury based on a solid research foundation...

Cardiovascular diseases (CVDs) have been established as a major cause of mortality globally. However, the exact pathogenesis remains obscure. N6-methyladenosine (m6 A) methylation is the most common epigenetic modification on mRNAs regulated by methyltransferase complexes (writers), demethylase transferases (erasers) and binding proteins (readers). It is now understood that m6 A is a major player in physiological and pathological cardiac processes. m6 A methylation are potentially involved in many mechanisms, for instance, regulation of calcium homeostasis, endothelial function, different forms of cell death, autophagy, endoplasmic reticulum stress, macrophage response and inflammation...