Competitive interaction between ATP and GTP regulates mitochondrial ATP-sensitive potassium channels.

Mitochondrial ATP-sensitive K channels (mitoKATP) have been recently characterized structurally, and possess a protein through which K enters mitochondria (MitoKIR), and a regulatory subunit (mitoSUR). The mitoSUR regulatory subunit is an ATP-binding cassette (ABC) protein isoform 8 (ABCB8). Opening these channels is known to be cardioprotective, but the molecular and physiological mechanisms that activate them are not fully known.

Effects of vitamin D (VD3) supplementation on the brain mitochondrial function of male rats, in the 6-OHDA-induced model of Parkinson's disease.

Mitochondria dysfunction is an important factor involved in PD pathogenesis. We reported neuroprotective actions of vitamin D (VD3) on a PD model, and now we investigated the VD3 effects on the brain mitochondrial function. We focused on oxygen consumption, respiratory control ratio (RCR), ADP/O ratio, mitochondria swelling, HO production, and SOD activity.

Calorie restriction changes lipidomic profiles and maintains mitochondrial function and redox balance during isoproterenol-induced cardiac hypertrophy.

Typically, healthy cardiac tissue utilizes more fat than any other organ. Cardiac hypertrophy induces a metabolic shift leading to a preferential consumption of glucose over fatty acids to support the high energetic demand. Calorie restriction is a dietary procedure that induces health benefits and lifespan extension in many organisms.

Pharmacological and molecular docking studies reveal that glibenclamide competitively inhibits diazoxide-induced mitochondrial ATP-sensitive potassium channel activation and pharmacological preconditioning.

Mitochondrial ATP-sensitive potassium channels (mitoKATP) locate in the inner mitochondrial membrane and possess protective cellular properties. mitoKATP opening-induced cardioprotection (using the pharmacological agent diazoxide) is preventable by antagonists, such as glibenclamide. However, the mechanisms of action of these drugs and how mitoKATP respond to them are poorly understood.

Cardiac hypertrophy drives PGC-1α suppression associated with enhanced O-glycosylation.

The peroxisome proliferator-activated receptor-gamma coactivator-1α (PGC-1α) regulates metabolism and is essential for normal cardiac function. Its activity is suppressed during pressure overload induced cardiac hypertrophy and such suppression at least partially contributes to the associated morbidity. The O-linked β-N-acetylglucosamine post-translational modification (O-GlcNAc) of proteins is a glucose-derived metabolic signal.

Quercetin treatment increases HO removal by restoration of endogenous antioxidant activity and blocks isoproterenol-induced cardiac hypertrophy.

Oxidative stress, characterized by the accumulation of reactive oxygen species (ROS), is implicated in the pathogenesis of several diseases, including cardiac hypertrophy. The flavonoid quercetin is a potent ROS scavenger, with several beneficial effects for the cardiovascular system, including antihypertrophic effects. Oxidative imbalance has been implicated in cardiac hypertrophy and heart failure.

Diazoxide Modulates Cardiac Hypertrophy by Targeting H2O2 Generation and Mitochondrial Superoxide Dismutase Activity.

Background: Cardiac hypertrophy involves marked wall thickening or chamber enlargement. If sustained, this condition will lead to dysfunctional mitochondria and oxidative stress. Mitochondria have ATP-sensitive K+ channels (mitoKATP) in the inner membrane that modulate the redox status of the cell.

Association between Epstein-Barr Virus and Oral Carcinoma: A Systematic Review with Meta-Analysis.

The purpose of this meta-analysis is to evaluate the association of Epstein-Barr virus (EBV) with oral squamous cell carcinoma (OSCC). We searched the electronic scientific databases of PubMed and Scopus and included a total of 53 studies that were published from 1990 to 2019. The analysis yielded a 45.

Calorie restriction attenuates hypertrophy-induced redox imbalance and mitochondrial ATP-sensitive K channel repression.

Oxidative stress has been implicated in the pathogenesis of cardiac hypertrophy and associated heart failure. Cardiac tissue grows in response to pressure or volume overload, leading to wall thickening or chamber enlargement. If sustained, this condition will lead to a dysfunctional cardiac tissue and oxidative stress.

Association between Epstein-Barr virus (EBV) and cervical carcinoma: A meta-analysis.

Objectives: Human papillomavirus (HPV) has been implicated as a major factor in cervical carcinogenesis. However, many pieces of evidence gathered over the last two decades suggest Epstein-Barr virus (EBV) plays a secondary role in this process. The purpose of the present meta-analysis was to determine whether the presence of EBV infection increases the risk of cervical carcinoma.

Diazoxide prevents reactive oxygen species and mitochondrial damage, leading to anti-hypertrophic effects.

Pathological cardiac hypertrophy is characterized by wall thickening or chamber enlargement of the heart in response to pressure or volume overload, respectively. This condition will, initially, improve the organ contractile function, but if sustained will render dysfunctional mitochondria and oxidative stress. Mitochondrial ATP-sensitive K channels (mitoKATP) modulate the redox status of the cell and protect against several cardiac insults.

High glucose induces mitochondrial dysfunction independently of protein O-GlcNAcylation.

Diabetes is characterized by hyperglycaemia and perturbations in intermediary metabolism. In particular, diabetes can augment flux through accessory pathways of glucose metabolism, such as the hexosamine biosynthetic pathway (HBP), which produces the sugar donor for the β-O-linked-N-acetylglucosamine (O-GlcNAc) post-translational modification of proteins. Diabetes also promotes mitochondrial dysfunction.

HASF is a stem cell paracrine factor that activates PKC epsilon mediated cytoprotection.

Despite advances in the treatment of acute tissue ischemia significant challenges remain in effective cytoprotection from ischemic cell death. It has been documented that injected stem cells, such as mesenchymal stem cells (MSCs), can confer protection to ischemic tissue through the release of paracrine factors. The study of these factors is essential for understanding tissue repair and the development of new therapeutic approaches for regenerative medicine.

O-GlcNAc signaling is essential for NFAT-mediated transcriptional reprogramming during cardiomyocyte hypertrophy.

The regulation of cardiomyocyte hypertrophy is a complex interplay among many known and unknown processes. One specific pathway involves the phosphatase calcineurin, which regulates nuclear translocation of the essential cardiac hypertrophy transcription factor, nuclear factor of activated T-cells (NFAT). Although metabolic dysregulation is frequently described during cardiac hypertrophy, limited insights exist regarding various accessory pathways.

O-linked β-N-acetylglucosamine transferase is indispensable in the failing heart.

The failing heart is subject to elevated metabolic demands, adverse remodeling, chronic apoptosis, and ventricular dysfunction. The interplay among such pathologic changes is largely unknown. Several laboratories have identified a unique posttranslational modification that may have significant effects on cardiovascular function.

Augmented O-GlcNAc signaling attenuates oxidative stress and calcium overload in cardiomyocytes.

O-linked β-N-acetylglucosamine (O-GlcNAc) is an inducible, dynamically cycling and reversible post-translational modification of Ser/Thr residues of nucleocytoplasmic and mitochondrial proteins. We recently discovered that O-GlcNAcylation confers cytoprotection in the heart via attenuating the formation of mitochondrial permeability transition pore (mPTP) and the subsequent loss of mitochondrial membrane potential. Because Ca(2+) overload and reactive oxygen species (ROS) generation are prominent features of post-ischemic injury and favor mPTP formation, we ascertained whether O-GlcNAcylation mitigates mPTP formation via its effects on Ca(2+) overload and ROS generation.

O-GlcNAc signaling in the cardiovascular system.

Cardiovascular function is regulated at multiple levels. Some of the most important aspects of such regulation involve alterations in an ever-growing list of posttranslational modifications. One such modification orchestrates input from numerous metabolic cues to modify proteins and alter their localization and/or function.

Unique hexosaminidase reduces metabolic survival signal and sensitizes cardiac myocytes to hypoxia/reoxygenation injury.

Metabolic signaling through the posttranslational linkage of N-acetylglucosamine (O-GlcNAc) to cellular proteins represents a unique signaling paradigm operative during lethal cellular stress and a pathway that we and others have recently shown to exert cytoprotective effects in vitro and in vivo. Accordingly, the present work addresses the contribution of the hexosaminidase responsible for removing O-GlcNAc (ie, O-GlcNAcase) from proteins. We used pharmacological inhibition, viral overexpression, and RNA interference of O-GlcNAcase in isolated cardiac myocytes to establish its role during acute hypoxia/reoxygenation.

Non-canonical glycosyltransferase modulates post-hypoxic cardiac myocyte death and mitochondrial permeability transition.

O-linked beta-N-acetylglucosamine (O-GlcNAc) is a dynamic, inducible, and reversible post-translational modification of nuclear and cytoplasmic proteins on Ser/Thr amino acid residues. In addition to its putative role as a nutrient sensor, we have recently shown pharmacologic elevation of O-GlcNAc levels positively affected myocyte survival during oxidant stress. However, no rigorous assessment of the contribution of O-GlcNAc transferase has been performed, particularly in the post-hypoxic setting.

Mitochondrial ATP-sensitive K+ channels are redox-sensitive pathways that control reactive oxygen species production.

Pharmacological mitochondrial ATP-sensitive K(+) channel (mitoK(ATP)) opening protects against ischemic damage and mimics ischemic preconditioning. However, physiological and pathological signaling events that open this channel are still not fully understood. We found that catalase, which removes H(2)O(2), is capable of reversing the beneficial effects of ischemic preconditioning but not of mitoK(ATP) agonist diazoxide.

Ischemic preconditioning requires increases in reactive oxygen release independent of mitochondrial K+ channel activity.

Mitochondrial ATP-sensitive K+ channels (mitoKATP) mediate ischemic preconditioning, a cardioprotective procedure. MitoKATP activity has been proposed to either enhance or prevent the release of reactive oxygen species. This study tested the redox effects of mitoKATP in order to clarify the role of these channels during preconditioning.

Tissue protection mediated by mitochondrial K+ channels.

Two distinct K+ uniporters have been described in mitochondria, ATP-sensitive and Ca2+-activated. Both are capable of protecting tissues against ischemia and other forms of injury when active. These findings indicate a central role for mitochondrial K+ uptake in tissue protection.

Mitochondrial ATP-sensitive K+ channels prevent oxidative stress, permeability transition and cell death.

Ischemia followed by reperfusion results in impairment of cellular and mitochondrial functionality due to opening of mitochondrial permeability transition pores. On the other hand, activation of mitochondrial ATP-sensitive K(+) channels (mitoK(ATP)) protects the heart against ischemic damage. This study examined the effects of mitoK(ATP) and mitochondrial permeability transition on isolated rat heart mitochondria and cardiac cells submitted to simulated ischemia and reperfusion (cyanide/aglycemia).