ArticleCardiovascular diabetology2013
Protein kinase RNA-like endoplasmic reticulum kinase (PERK) signaling pathway plays a major role in reactive oxygen species (ROS)-mediated endoplasmic reticulum stress-induced apoptosis in diabetic cardiomyopathy.
Article in Cardiovascular diabetology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 116 papers, 1 of them a synthesis that pooled it.
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Who cites it
116 citing papers in PubMed, 1 synthesis or guideline pooled it, 205 citations in OpenAlex.
- MAM kinases: physiological roles, related diseases, and therapeutic perspectives-a systematic review.Cellular & molecular biology letters · 2025Pooled it
- Heavy metal toxicity as a driver of endoplasmic reticulum stress and dysfunction.The FEBS journal · 2026Review
- Single-cell transcriptomic profiling reveals PDK4 upregulation and impaired VEGF-C/VEGFR3 signaling in cardiac lymphatic endothelial cells in diabetic cardiomyopathy.Molecular medicine (Cambridge, Mass.) · 2026Article
- Organelle homeostasis disruption: A driving force in the progression of cardiomyopathy (Review).Experimental and therapeutic medicine · 2026Review
- In silico analysis of PERK interactions with engineered alpha lactalbumin peptides using molecular dynamics simulations.Scientific reports · 2026Article
- GULP1 protects against diabetic cardiomyopathy through IKIP/NF-κB-dependent improvement of mitochondrial function.Cardiovascular diabetology · 2026Article
- Lipid droplets beyond storage: Cellular metabolic modulator in the diabetic heart (Review).International journal of molecular medicine · 2026Review
- Targeting Mitochondria-Associated Endoplasmic Reticulum Membranes (MAMs): A Novel Therapeutic Strategy for Diabetic Complications.Diabetes, metabolic syndrome and obesity : targets and therapy · 2026Review
- Tangeretin prevents cardiac failure induced by reperfusion/ischaemia by inhibiting apoptosis, endoplasmic reticulum stress, and JNK/ERK pathway.Archives of medical science : AMS · 2026Article
- Hypoxia-triggered autophagy modulates cisplatin resistance in non-small cell lung Cancer via EIF2AK3-dependent PI3K/AKT signaling and mTOR-independent mechanisms.Cell death discovery · 2025Article
- Mitochondria-Associated Endoplasmic Reticulum Membranes as Potential Therapeutic Targets in Epilepsy.CNS neuroscience & therapeutics · 2025Review
- Hydrogen Sulfide (HAntioxidants (Basel, Switzerland) · 2025Article
- Metabolic Adaptations and Therapies in Cardiac Hypoxia: Mechanisms and Clinical Implications/ Potential Strategies.JACC. Basic to translational science · 2025Review
- Mechanisms and Targeted Therapeutic Strategies in Sepsis-Induced Myocardial Dysfunction: The Role of NLRP3 Inflammasome-Mediated Inflammation.Journal of inflammation research · 2025Review
- Identification and validation of endoplasmic reticulum stress-related diagnostic biomarkers for type 1 diabetic cardiomyopathy based on bioinformatics and machine learning.Frontiers in endocrinology · 2025Article
- Regulated Cell Death Pathways in Pathological Cardiac Hypertrophy.Reviews in cardiovascular medicine · 2024Review
- Redox regulation of UPR signalling and mitochondrial ER contact sites.Cellular and molecular life sciences : CMLS · 2024Review
- Harnessing the Synergy of SGLT2 Inhibitors and Continuous Ketone Monitoring (CKM) in Managing Heart Failure among Patients with Type 1 Diabetes.Healthcare (Basel, Switzerland) · 2024Review
- Mitochondria-associated endoplasmic reticulum membrane (MAM): a dark horse for diabetic cardiomyopathy treatment.Cell death discovery · 2024Review
- Relevance of the endoplasmic reticulum-mitochondria axis in cancer diagnosis and therapy.Experimental & molecular medicine · 2024Review
56 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundEndoplasmic reticulum (ER) stress is considered one of the mechanisms contributing to reactive oxygen species (ROS)-mediated cell apoptosis. In diabetic cardiomyopathy (DCM), cell apoptosis is generally accepted as the etiological factor and closely related to cardiac ROS generation. ER stress is proposed the link between ROS and cell apoptosis; however, the signaling pathways and their roles in participating ER stress-induced apoptosis in DCM are still unclear.
methodsIn this study, we investigated the signaling transductions in ROS-dependent ER stress-induced cardiomocyte apoptosis in animal model of DCM. Moreover, in order to clarify the roles of IRE1 (inositol-requiring enzyme-1), PERK (protein kinase RNA (PKR)-like ER kinase) and ATF6 (activating transcription factor-6) in conducting apoptotic signal in ROS- dependent ER stress-induced cardiomocyte apoptosis, we further investigated apoptosis in high-glucose incubated cardiomyocytes with IRE1, ATF6 and PERK-knocked down respectively.
resultswe demonstrated that the ER stress sensors, referred as PERK, IRE1 and ATF6, were activated in ROS-mediated ER stress-induced cell apoptosis in rat model of DCM which was characterized by cardiac pump and electrical dysfunctions. The deletion of PERK in myocytes exhibited stronger protective effect against apoptosis induced by high-glucose incubation than deletion of ATF6 or IRE in the same myocytes. By subcellular fractionation, rather than ATF6 and IRE1, in primary cardiomyocytes, PERK was found a component of MAMs (mitochondria-associated endoplasmic reticulum membranes) which was the functional and physical contact site between ER and mitochondria.
conclusionsROS-stimulated activation of PERK signaling pathway takes the major responsibility rather than IRE1 or ATF6 signaling pathways in ROS-medicated ER stress-induced myocyte apoptosis in DCM.
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