Low neuronal metabolism during isoflurane-induced burst suppression is related to synaptic inhibition while neurovascular coupling and mitochondrial function remain intact

Deep anaesthesia may impair neuronal, vascular and mitochondrial function facilitating neurological complications, such as delirium and stroke. On the other hand, deep anaesthesia is performed for neuroprotection in critical brain diseases such as status epilepticus or traumatic brain injury. Since the commonly used anaesthetic propofol causes mitochondrial dysfunction, we investigated the impact of the alternative anaesthetic isoflurane on neuro-metabolism. In deeply anaesthetised Wistar rats (burst suppression pattern), we measured increased cortical tissue oxygen pressure (ptiO2), a ∼35% drop in regional cerebral blood flow (rCBF) and burst-associated neurovascular responses. In vitro, 3% isoflurane blocked synaptic transmission and impaired network oscillations, thereby decreasing the cerebral metabolic rate of oxygen (CMRO2). Concerning mitochondrial function, isoflurane induced a reductive shift in flavin adenine dinucleotide (FAD) and decreased stimulus-induced FAD transients as Ca2+ influx was reduced by ∼50%. Computer simulations based on experimental results predicted no direct effects of isoflurane on mitochondrial complexes or ATP-synthesis. We found that isoflurane-induced burst suppression is related to decreased ATP consumption due to inhibition of synaptic activity while neurovascular coupling and mitochondrial function remain intact. The neurometabolic profile of isoflurane thus appears to be superior to that of propofol which has been shown to impair the mitochondrial respiratory chain.

Download Full-text

Abstract 355: Effect of Poloxamer 188 on Rat Brain Isolated Mitochondria After Exposure to Hydrogen Peroxide

Circulation ◽

10.1161/circ.140.suppl_2.355 ◽

2019 ◽

Vol 140 (Suppl_2) ◽

Author(s):

Johannes A Pille ◽

Michele M Salzman ◽

Anna A Sonju ◽

Felicia P Lotze ◽

Josephine E Hees ◽

...

Keyword(s):

Hydrogen Peroxide ◽

Oxygen Consumption ◽

Mitochondrial Function ◽

Complex I ◽

Room Temperature ◽

In Vitro Model ◽

Atp Synthesis ◽

Complex Ii ◽

Vitro Model

Introduction: In a pig model of myocardial infarction (MI), intracoronary delivered Poloxamer (P) 188 significantly reduces ischemia/reperfusion (IR) injury when given immediately upon reperfusion, with improved mitochondrial function as a predominant effect. As mitochondria are heavily damaged during IR, a direct effect of P188 on mitochondria may lead to better therapy options during reperfusion. To show not only a similar reduction of IR injury by P188 in the brain, but also a direct P188 effect on mitochondria, we established an in-vitro model of IR that consists of damaging isolated rat brain mitochondria with hydrogen peroxide (H 2 O 2 ), one component of ischemia, then applying P188, and analyzing mitochondrial function. Methods: Male Sprague-Dawley rat brains were removed, and the mitochondria isolated by differential centrifugation and Percoll gradients, then kept on ice to slow their bioenergetics prior to any experimental treatments. Mitochondria were exposed to 200 μM H 2 O 2 for 10 min at room temperature with slight agitation; controls received no H 2 O 2 . Samples were then diluted ½ with buffer ± P188 (250 μM after dilution) to simulate reperfusion and treatment, and kept at room temperature for 10 further minutes. ATP synthesis was measured in a luminometer using a luciferase enzymatic assay. Oxygen consumption was measured by closed cell respirometry with an oxygen meter. In both assays, Complex I and Complex II were examined; Complex I substrates glutamate and malate, Complex II substrate succinate plus the Complex I inhibitor rotenone. Statistics: Data are expressed as mean ± SEM. One-Way ANOVA, SNK-Test; Kruskal-Wallis-Test; α=0.05, * vs control. Results: In both Complex I and II, mitochondrial function was significantly impaired by H 2 O 2 , with ATP synthesis affected more at Complex I and oxygen consumption affected more at Complex II. Addition of P188 did not provide any significant improvement in mitochondrial function. Conclusions: Although P188 significantly reduced IR injury when given during reperfusion in a pig model of MI, it does not appear to provide direct protection to mitochondria in this in-vitro model. Whether the exposure to H 2 O 2 causes the appropriate injury for P188 to become effective remains to be elucidated.

Download Full-text

Asymmetric Arginine Dimethylation Modulates Mitochondrial Energy Metabolism and Homeostasis in Caenorhabditis elegans

Molecular and Cellular Biology ◽

10.1128/mcb.00504-16 ◽

2016 ◽

Vol 37 (6) ◽

Cited By ~ 6

Author(s):

Liang Sha ◽

Hiroaki Daitoku ◽

Sho Araoi ◽

Yuta Kaneko ◽

Yuta Takahashi ◽

...

Keyword(s):

Caenorhabditis Elegans ◽

Mitochondrial Function ◽

Atp Synthesis ◽

Subcellular Fractionation ◽

Mitochondrial Energy Metabolism ◽

Content Type ◽

Liquid Chromatography Tandem Mass ◽

Protein Arginine Methyltransferase 1

ABSTRACT Protein arginine methyltransferase 1 (PRMT-1) catalyzes asymmetric arginine dimethylation on cellular proteins and modulates various aspects of biological processes, such as signal transduction, DNA repair, and transcriptional regulation. We have previously reported that the null mutant of prmt-1 in Caenorhabditis elegans exhibits a slightly shortened life span, but the physiological significance of PRMT-1 remains largely unclear. Here we explored the role of PRMT-1 in mitochondrial function as hinted by a two-dimensional Western blot-based proteomic study. Subcellular fractionation followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis showed that PRMT-1 is almost entirely responsible for asymmetric arginine dimethylation on mitochondrial proteins. Importantly, isolated mitochondria from prmt-1 mutants represent compromised ATP synthesis in vitro, and whole-worm respiration in prmt-1 mutants is decreased in vivo. Transgenic rescue experiments demonstrate that PRMT-1-dependent asymmetric arginine dimethylation is required to prevent mitochondrial reactive oxygen species (ROS) production, which consequently causes the activation of the mitochondrial unfolded-protein response. Furthermore, the loss of enzymatic activity of prmt-1 induces food avoidance behavior due to mitochondrial dysfunction, but treatment with the antioxidant N-acetylcysteine significantly ameliorates this phenotype. These findings add a new layer of complexity to the posttranslational regulation of mitochondrial function and provide clues for understanding the physiological roles of PRMT-1 in multicellular organisms.

Download Full-text

The effects in vitro of TNF-α and its antagonist ‘etanercept’ on ejaculated human sperm

Reproduction Fertility and Development ◽

10.1071/rd16090 ◽

2017 ◽

Vol 29 (6) ◽

pp. 1169 ◽

Cited By ~ 4

Author(s):

Nicola A. Pascarelli ◽

Antonella Fioravanti ◽

Elena Moretti ◽

Giacomo M. Guidelli ◽

Lucia Mazzi ◽

...

Keyword(s):

Mitochondrial Function ◽

In Vitro Study ◽

Human Sperm ◽

Dna Integrity ◽

Sperm Function ◽

Sperm Viability ◽

Tnf Α ◽

The Impact

Tumour necrosis factor (TNF)-α is primarily involved in the regulation of cell proliferation and apoptosis; in addition it possesses pro-inflammatory properties. Anti-TNF-α strategies involve either administration of anti-TNF-α antibody or soluble TNF receptor to mop up circulating TNF-α. Etanercept, a recombinant human TNF-α receptor, was found to be effective in the treatment of rheumatoid arthritis. The impact of TNF-α inhibitors on human fertility is of notable interest. This in vitro study investigated the effect of different concentrations of TNF-α and etanercept used alone or in combination on sperm viability, motility, mitochondrial function, percentage of apoptosis and chromatin integrity in swim-up selected human spermatozoa. A negative effect of TNF-α (300 and 500 ng mL–1) and etanercept (from 800 µg mL–1 to 2000 µg mL–1) individually on sperm viability, motility, mitochondrial function, percentage of apoptotic spermatozoa and sperm DNA integrity was demonstrated. However, at concentrations of 100 and 200 µg mL–1, etanercept can block, in a significant way, the toxic effects of TNF-α (500 ng mL–1) on studied sperm characteristics. Our results confirm that TNF-α has a detrimental effect on sperm function and suggest, for the first time, that etanercept may counteract the in vitro toxic action of TNF-α. This data appears to be quite promising, although further studies, both in vivo and in vitro, are needed to understand the exact mechanism of action of TNF-α and TNF-α antagonists on sperm function.

Download Full-text

THE IMPACT OF CARDIOVASCULAR AND BRONCHOPULMONARY DISEASES ON COENZYME Q10 PLASMA CONCENTRATION

Sechenov Medical Journal ◽

10.47093/22187332.2019.1.16-21 ◽

2019 ◽

Vol 10 (1) ◽

pp. 16-21

Author(s):

V. I. Zozina ◽

E. S. Melnikov ◽

L. M. Krasnykh ◽

O. A. Goroshko ◽

V. G. Kukes

Keyword(s):

Coenzyme Q10 ◽

High Performance ◽

Sharp Decrease ◽

Atp Synthesis ◽

Mitochondrial Respiratory Chain ◽

Pulmonary Diseases ◽

Main Function ◽

Bronchopulmonary Diseases ◽

The Impact ◽

The Relationship

Introduction. Coenzyme Q10 plays an important role in the human body. Its main function is not only the transfer of electrons in the mitochondrial respiratory chain for the ATP synthesis, but it is also one of the most powerful antioxidants in the body.The aim of research is to monitor the relationship between cardiovascular and pulmonary diseases, and the concentration of coenzyme Q10 in the blood plasma.Materials and methods. Coenzyme Q10 was determined using high performance liquid chromatography with mass spectrometric detection.Results and discussion. During the study, it was found that the concentration of coenzyme Q10 in plasma is aﬀected not only by the main diseases, but also by comorbidities, as well as by the therapy. A sharp decrease in plasma coenzyme Q10 concentration was noted in patients with cardiovascular pathologies, especially in those with concomitant endocrine diseases. Also, it was recorded a decrease in the concentration of coenzyme Q10 in the plasma of patients with pneumonia. Conclusion. During the experiment, the coenzyme Q10 concentration was found to be dependent on cardiovascular and pulmonary diseases.

Download Full-text

Mitochondrial respiratory chain inhibition and Na+K+ATPase dysfunction are determinant factors modulating the toxicity of nickel in the brain of indian catfish Clarias batrachus L.

Interdisciplinary Toxicology ◽

10.2478/intox-2018-0030 ◽

2018 ◽

Vol 11 (4) ◽

pp. 306-315 ◽

Cited By ~ 1

Author(s):

Arpan Kumar Maiti ◽

Nimai Chandra Saha ◽

Goutam Paul ◽

Kishore Dhara

Keyword(s):

Respiratory Chain ◽

Mitochondrial Function ◽

Mitochondrial Respiratory Chain ◽

Clarias Batrachus ◽

Contributing Factors ◽

Functional Changes ◽

Partial Inhibition ◽

Mitochondrial Functions ◽

The Impact ◽

Mitochondrial Respiratory

Abstract Nickel is a potential neurotoxic pollutant inflicting damage in living organisms, including fish, mainly through oxidative stress. Previous studies have demonstrated the impact of nickel toxicity on mitochondrial function, but there remain lacunae on the damage inflicted at mitochondrial respiratory level. Deficient mitochondrial function usually affects the activities of important adenosinetriphosphatases responsible for the maintenance of normal neuronal function, namely Na+K+ATPase, as explored in our study. Previous reports demonstrated the dysfunction of this enzyme upon nickel exposure but the contributing factors for the inhibition of this enzyme remained unexplored. The main purpose of this study was to elucidate the impact of nickel neurotoxicity on mitochondrial respiratory complexes and Na+K+ATPase in the piscine brain and to determine the contributing factors that had an impact on the same. Adult Clarias batrachus were exposed to nickel treated water at 10% and 20% of the 96 h LC50 value (41 mg.l−1) respectively and sampled on 20, 40 and 60 days. Exposure of fish brain to nickel led to partial inhibition of complex IV of mitochondrial respiratory chain, however, the activities of complex I, II and III remained unaltered. This partial inhibition of mitochondrial respiratory chain might have been sufficient to lower mitochondrial energy production in mitochondria that contributed to the partial dysfunction of Na+K+ATPase. Besides energy depletion other contributing factors were involved in the dysfunction of this enzyme, like loss of thiol groups for enzyme activity and lipid peroxidation-derived end products that might have induced conformational and functional changes. However, providing direct evidence for such conformational and functional changes of Na+K+ATPase was beyond the scope of the present study. In addition, immunoblotting results also showed a decrease in Na+K+ATPase protein expression highlighting the impact of nickel neurotoxicity on the expression of the enzyme itself. The implication of the inhibition of mitochondrial respiration and Na+K+ATPase dysfunction was the neuronal death as evidenced by enhanced caspase-3 and caspase-9 activities. Thus, this study established the deleterious impact of nickel neurotoxicity on mitochondrial functions in the piscine brain and identified probable contributing factors that can act concurrently in the inhibition of Na+K+ATPase. This study also provided a vital clue about the specific areas that the therapeutic agents should target to counter nickel neurotoxicity.

Download Full-text

Dihydromyricetin Attenuates Dexamethasone-Induced Muscle Atrophy by Improving Mitochondrial Function via the PGC-1α Pathway

Cellular Physiology and Biochemistry ◽

10.1159/000493040 ◽

2018 ◽

Vol 49 (2) ◽

pp. 758-779 ◽

Cited By ~ 15

Author(s):

Yujie Huang ◽

Ka Chen ◽

Qingbo Ren ◽

Long Yi ◽

Jundong Zhu ◽

...

Keyword(s):

Muscle Atrophy ◽

Mitochondrial Function ◽

Chain Complex ◽

Mitochondrial Respiratory Chain ◽

Mitochondrial Morphology ◽

Cross Sectional ◽

Mitochondrial Respiratory Chain Complex ◽

Underlying Mechanisms ◽

Complex Activities

Background/Aims: Skeletal muscle atrophy is an important health issue and can impose tremendous economic burdens on healthcare systems. Glucocorticoids (GCs) are well-known factors that result in muscle atrophy observed in numerous pathological conditions. Therefore, the development of effective and safe therapeutic strategies for GC-induced muscle atrophy has significant clinical implications. Some natural compounds have been shown to effectively prevent muscle atrophy under several wasting conditions. Dihydromyricetin (DM), the most abundant flavonoid in Ampelopsis grossedentata, has a broad range of health benefits, but its effects on muscle atrophy are unclear. The purpose of this study was to evaluate the effects and underlying mechanisms of DM on muscle atrophy induced by the synthetic GC dexamethasone (Dex). Methods: The effects of DM on Dex-induced muscle atrophy were assessed in Sprague-Dawley rats and L6 myotubes. Muscle mass and myofiber cross-sectional areas were analyzed in gastrocnemius muscles. Muscle function was evaluated by a grip strength test. Myosin heavy chain (MHC) content and myotube diameter were measured in myotubes. Mitochondrial morphology was observed by transmission electron microscopy and confocal laser scanning microscopy. Mitochondrial DNA (mtDNA) was quantified by real-time PCR. Mitochondrial respiratory chain complex activities were examined using the MitoProfile Rapid Microplate Assay Kit, and mitochondrial membrane potential was assessed by JC-1 staining. Protein levels of mitochondrial biogenesis and dynamics markers were detected by western blotting. Myotubes were transfected with siRNAs targeting peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), mitochondrial transcription factor A (TFAM) and mitofusin-2 (mfn2) to determine the underlying mechanisms. Results: In vivo, DM preserved muscles from weight and average fiber cross-sectional area losses and improved grip strength. In vitro, DM prevented the decrease in MHC content and myotube diameter. Moreover, DM stimulated mitochondrial biogenesis and promoted mitochondrial fusion, rescued the reduced mtDNA content, improved mitochondrial morphology, prevented the collapse in mitochondrial membrane potential and enhanced mitochondrial respiratory chain complex activities; these changes restored mitochondrial function and improved protein metabolism, contributing to the prevention of Dex-induced muscle atrophy. Furthermore, the protective effects of DM on mitochondrial function and muscle atrophy were alleviated by PGC-1α siRNA, TFAM siRNA and mfn2 siRNA transfection in vitro. Conclusion: DM attenuated Dex-induced muscle atrophy by reversing mitochondrial dysfunction, which was partially mediated by the PGC-1α/TFAM and PGC-1α/mfn2 signaling pathways. Our findings may open new avenues for identifying natural compounds that improve mitochondrial function as promising candidates for the management of muscle atrophy.

Download Full-text

Abstract 330: No Direct Mitochondrial Protection Against Ischemia Reperfusion Injury in Rat Isolated Hearts by P188 Postconditioning

Circulation ◽

10.1161/circ.142.suppl_4.330 ◽

2020 ◽

Vol 142 (Suppl_4) ◽

Author(s):

Josephine Eskaf ◽

Luise J Meyer ◽

William J Cleveland ◽

Zhu Li ◽

Matthias L Riess

Keyword(s):

Oxygen Consumption ◽

Mitochondrial Function ◽

Ischemia Reperfusion Injury ◽

Ex Vivo ◽

Ischemia Reperfusion ◽

Atp Synthesis ◽

Protective Effects ◽

Sprague Dawley ◽

Retention Capacity

Introduction: Myocardial infarction and cardiac arrest lead to ischemia-reperfusion (IR) injury in the heart. Timely reperfusion through percutaneous coronary intervention and cardiopulmonary resuscitation, respectively, reduces ischemia but also exacerbates myocardial injury. Maintaining mitochondrial function is crucial in maintaining cardiomyocyte function in IR injury. Poloxamer 188 (P188) is a triblock copolymer that has shown protective effects in in-vitro, ex-vivo and in-vivo myocardial IR models. P188 is thought to improve cellular and mitochondrial function during IR by stabilizing membranes. Hypothesis: P188 postconditioning has direct protective effects on mitochondrial function as assessed by ATP synthesis, oxygen consumption and calcium retention capacity (CRC). Methods: After approval by the local authorities, hearts of 42 adult male Sprague-Dawley rats were isolated and perfused ex-vivo with oxygenated Krebs Buffer (KB) for 20 min before 30 min of no-flow ischemia. Hearts were reperfused for 10 min with KB. Cardiac mitochondria were isolated with 1 mM P188 vs 1 mM polyethylene glycol (PEG) vs vehicle by differential centrifugation. Mitochondrial function was assessed for complex I and II substrates of the respiratory chain. Statistics: Kruskal-Wallis with Dunn’s posthoc testing; alpha=0.05. Results: Mitochondrial function decreased significantly after ischemia and showed improvement with reperfusion. P188 did not result in significant improvements in mitochondrial ATP synthesis, oxygen consumption and CRC function after IR, and neither did PEG. Conclusions: P188 does not have a direct protective effect on mitochondria in this model. This might be owed to the fact that no additional damage could be observed after reperfusion which is the type of injury targeted by P188 post-conditioning.

Download Full-text

Age-Related EEG Features of Bursting Activity During Anesthetic-Induced Burst Suppression

Frontiers in Systems Neuroscience ◽

10.3389/fnsys.2020.599962 ◽

2020 ◽

Vol 14 ◽

Author(s):

Stephan Kratzer ◽

Michael Schneider ◽

David P. Obert ◽

Gerhard Schneider ◽

Paul S. García ◽

...

Keyword(s):

Burst Suppression ◽

Synaptic Activity ◽

Permutation Entropy ◽

Anesthesia Care ◽

Alpha Band ◽

Old Patients ◽

Initial Burst ◽

Band Power ◽

Age Related ◽

The Impact

Electroencephalographic (EEG) Burst Suppression (BSUPP) is a discontinuous pattern characterized by episodes of low voltage disrupted by bursts of cortical synaptic activity. It can occur while delivering high-dose anesthesia. Current research suggests an association between BSUPP and the occurrence of postoperative delirium in the post-anesthesia care unit (PACU) and beyond. We investigated burst micro-architecture to further understand how age influences the neurophysiology of this pharmacologically-induced state. We analyzed a subset of EEG recordings (n = 102) taken from a larger data set previously published. We selected the initial burst that followed a visually identified “silent second,” i.e., at least 1 s of iso-electricity of the EEG during propofol induction. We derived the (normalized) power spectral density [(n)PSD], the alpha band power, the maximum amplitude, the maximum slope of the EEG as well as the permutation entropy (PeEn) for the first 1.5 s of the initial burst of each patient. In the old patients >65 years, we observed significantly lower (p < 0.001) EEG power in the 1–15 Hz range. In general, their EEG contained a significantly higher amount of faster oscillations (>15 Hz). Alpha band power (p < 0.001), EEG amplitude (p = 0.001), and maximum EEG slope (p = 0.045) all significantly decreased with age, whereas PeEn increased (p = 0.008). Hence, we can describe an age-related change in features during EEG burst suppression. Sub-group analysis revealed no change in results based on pre-medication. These EEG changes add knowledge to the impact of age on cortical synaptic activity. In addition to a reduction in EEG amplitude, age-associated burst features can complicate the identification of excessive anesthetic administration in patients under general anesthesia. Knowledge of these neurophysiologic changes may not only improve anesthesia care through improved detection of burst suppression but might also provide insight into changes in neuronal network organization in patients at risk for age-related neurocognitive problems.

Download Full-text

Larix laricina, an Antidiabetic Alternative Treatment from the Cree of Northern Quebec Pharmacopoeia, Decreases Glycemia and Improves Insulin SensitivityIn Vivo

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2012/296432 ◽

2012 ◽

Vol 2012 ◽

pp. 1-10 ◽

Cited By ~ 10

Author(s):

Despina Harbilas ◽

Diane Vallerand ◽

Antoine Brault ◽

Ammar Saleem ◽

John T. Arnason ◽

...

Keyword(s):

Mitochondrial Function ◽

Treatment Protocol ◽

Atp Synthesis ◽

Larix Laricina ◽

Prevention Study ◽

Promising Alternative ◽

Bay Area ◽

Obesity And Diabetes ◽

Traditional Pharmacopoeia

Larix laricinaK. Koch is a medicinal plant belonging to traditional pharmacopoeia of the Cree of Eeyou Istchee (Eastern James Bay area of Canada).In vitroscreening studies revealed that, like metformin and rosiglitazone, it increases glucose uptake and adipogenesis, activates AMPK, and uncouples mitochondrial function. The objective of this study was to evaluate the antidiabetic and antiobesity potential ofL. laricinain diet-induced obese (DIO) C57BL/6 mice. Mice were subjected for eight or sixteen weeks to a high fat diet (HFD) or HFD to whichL. laricinawas incorporated at 125 and 250 mg/kg either at onset (prevention study) or in the last 8 of the 16 weeks of administration of the HFD (treatment study).L. laricinaeffectively decreased glycemia levels, improved insulin resistance, and slightly decreased abdominal fat pad and body weights. This occurred in conjunction with increased energy expenditure as demonstrated by elevated skin temperature in the prevention study and improved mitochondrial function and ATP synthesis in the treatment protocol.L. laricinais thus a promising alternative and complementary therapeutic approach for the treatment and care of obesity and diabetes among the Cree.

Download Full-text

Capsaicin Alleviates the Deteriorative Mitochondrial Function by Upregulating 14-3-3η in Anoxic or Anoxic/Reoxygenated Cardiomyocytes

Oxidative Medicine and Cellular Longevity ◽

10.1155/2020/1750289 ◽

2020 ◽

Vol 2020 ◽

pp. 1-16 ◽

Cited By ~ 1

Author(s):

Yang Qiao ◽

Tianhong Hu ◽

Bin Yang ◽

Hongwei Li ◽

Tianpeng Chen ◽

...

Keyword(s):

Mitochondrial Function ◽

Complex I ◽

Redox Homeostasis ◽

Redox Status ◽

Neonatal Rat ◽

Ros Generation ◽

Consumption Rates ◽

Vitro Model ◽

The Impact

Reactive oxygen species (ROS) are byproducts of a defective electron transport chain (ETC). The redox couples, GSH/GSSG and NAD+/NADH, play an essential role in physiology as internal defenses against excessive ROS generation by facilitating intracellular/mitochondrial (mt) redox homeostasis. Anoxia alone and anoxia/reoxygenation (A/R) are dissimilar pathological processes. In this study, we measured the impact of capsaicin (Cap) on these pathological processes using a primary cultured neonatal rat cardiomyocyte in vitro model. The results showed that overproduction of ROS was tightly associated with disturbed GSH/GSSG and NAD+/NADH suppressed mt complex I and III activities, decreased oxygen consumption rates, and elevated extracellular acidification rates. During anoxia or A/R period, these indices interact with each other causing the mitochondrial function to worsen. Cap protected cardiomyocytes against the different stages of A/R injury by rescuing NAD+/NADH, GSH/GSSG, and mt complex I/III activities and cellular energy metabolism. Importantly, Cap-mediated upregulation of 14-3-3η, a protective phosphoserine-binding protein in cardiomyocytes, ameliorated mt function caused by a disruptive redox status and an impaired ETC. In conclusion, redox pair, mt complex I/III, and metabolic equilibrium were significantly different in anoxia alone and A/R injury; Cap through upregulating 14-3-3η plays a protection against the above injury in cardiomyocyte.

Download Full-text