ArticleJournal of cellular physiology2011
PKCε promotes cardiac mitochondrial and metabolic adaptation to chronic hypobaric hypoxia by GSK3β inhibition.
Article in Journal of cellular physiology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
15 citing papers in PubMed, 23 citations in OpenAlex.
- Zapotin mitigates breast cancer progression by targeting PKCε mediated glycolytic pathway regulation.BMC cancer · 2025Article
- Exosomal Preconditioning of Human iPSC-Derived Cardiomyocytes Beneficially Alters Cardiac Electrophysiology and Micro RNA Expression.International journal of molecular sciences · 2024Article
- PKCε inhibition prevents ischemia‑induced dendritic spine impairment in cultured primary neurons.Experimental and therapeutic medicine · 2023Article
- The effect of an adaptation to hypoxia on cardiac tolerance to ischemia/reperfusion.Journal of biomedical research · 2022Article
- Adaptive Cardiac Metabolism Under Chronic Hypoxia: Mechanism and Clinical Implications.Frontiers in cell and developmental biology · 2021Review
- The involvement of protein kinases in the cardioprotective effect of chronic hypoxia.Physiological research · 2020Review
- Nox2 Upregulation and p38α MAPK Activation in Right Ventricular Hypertrophy of Rats Exposed to Long-Term Chronic Intermittent Hypobaric Hypoxia.International journal of molecular sciences · 2020Article
- Oxidative Stress, Kinase Activity and Inflammatory Implications in Right Ventricular Hypertrophy and Heart Failure under Hypobaric Hypoxia.International journal of molecular sciences · 2020Review
- Cardioprotection by intermittent hypoxia conditioning: evidence, mechanisms, and therapeutic potential.American journal of physiology. Heart and circulatory physiology · 2018Review
- Atorvastatin Attenuates Myocardial Hypertrophy Induced by Chronic Intermittent Hypoxia In Vitro Partly through miR-31/PKCε Pathway.Current medical science · 2018Article
- On the pivotal role of PPARα in adaptation of the heart to hypoxia and why fat in the diet increases hypoxic injury.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2016Article
- Increased expression of estrogen-related receptor β during adaptation of adult cardiomyocytes to sustained hypoxia.American journal of cardiovascular disease · 2016Article
- Effect of regional muscle location but not adiposity on mitochondrial biogenesis-regulating proteins.European journal of applied physiology · 2016Article
- Mechanism for reduced pericardial adhesion formation in hypercholesterolemic swine supplemented with alcohol.European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery · 2013Article
- Impaired cardiac ischemic tolerance in spontaneously hypertensive rats is attenuated by adaptation to chronic and acute stress.Experimental and clinical cardiology · 2011Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
PKCε is central to cardioprotection. Sub-proteome analysis demonstrated co-localization of activated cardiac PKCε (aPKCε) with metabolic, mitochondrial, and cardioprotective modulators like hypoxia-inducible factor 1α (HIF-1α). aPKCε relocates to the mitochondrion, inactivating glycogen synthase kinase 3β (GSK3β) to modulate glycogen metabolism, hypertrophy and HIF-1α. However, there is no established mechanistic link between PKCε, p-GSK3β and HIF1-α. Here we hypothesized that cardiac-restricted aPKCε improves mitochondrial response to hypobaric hypoxia by altered substrate fuel selection via a GSK3β/HIF-1α-dependent mechanism. aPKCε and wild-type (WT) mice were exposed to 14 days of hypobaric hypoxia (45 kPa, 11% O(2)) and cardiac metabolism, functional parameters, p-GSK3β/HIF-1α expression, mitochondrial function and ultrastructure analyzed versus normoxic controls. Mitochondrial ADP-dependent respiration, ATP production and membrane potential were attenuated in hypoxic WT but maintained in hypoxic aPKCε mitochondria (P < 0.005, n = 8). Electron microscopy revealed a hypoxia-associated increase in mitochondrial number with ultrastructural disarray in WT versus aPKCε hearts. Concordantly, left ventricular work was diminished in hypoxic WT but not aPKCε mice (glucose only perfusions). However, addition of palmitate abrogated this (P < 0.05 vs. WT). aPKCε hearts displayed increased glucose utilization at baseline and with hypoxia. In parallel, p-GSK3β and HIF1-α peptide levels were increased in hypoxic aPKCε hearts versus WT. Our study demonstrates that modest, sustained PKCε activation blunts cardiac pathophysiologic responses usually observed in response to chronic hypoxia. Moreover, we propose that preferential glucose utilization by PKCε hearts is orchestrated by a p-GSK3β/HIF-1α-mediated mechanism, playing a crucial role to sustain contractile function in response to chronic hypobaric hypoxia.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.