scholarly journals Mitochondrion as a Target of Astaxanthin Therapy in Heart Failure

2021 ◽  
Vol 22 (15) ◽  
pp. 7964
Author(s):  
Olga Krestinina ◽  
Yulia Baburina ◽  
Roman Krestinin
Keyword(s):  
Oxidative Damage ◽  
Mitochondrial Permeability Transition ◽  
Heart Diseases ◽  
Permeability Transition Pore ◽  
Chronic Administration ◽  
Permeability Transition ◽  
Pathological Conditions ◽  
Mitochondrial Target ◽  
Rat Heart Mitochondria ◽  
Mitochondrial Efficiency

Mitochondria are considered to be important organelles in the cell and play a key role in the physiological function of the heart, as well as in the pathogenesis and development of various heart diseases. Under certain pathological conditions, such as cardiovascular diseases, stroke, traumatic brain injury, neurodegenerative diseases, muscular dystrophy, etc., mitochondrial permeability transition pore (mPTP) is formed and opened, which can lead to dysfunction of mitochondria and subsequently to cell death. This review summarizes the results of studies carried out by our group of the effect of astaxanthin (AST) on the functional state of rat heart mitochondria upon direct addition of AST to isolated mitochondria and upon chronic administration of AST under conditions of mPTP opening. It was shown that AST exerted a protective effect under all conditions. In addition, AST treatment was found to prevent isoproterenol-induced oxidative damage to mitochondria and increase mitochondrial efficiency. AST, a ketocarotenoid, may be a potential mitochondrial target in therapy for pathological conditions associated with oxidative damage and mitochondrial dysfunction, and may be a potential mitochondrial target in therapy for pathological conditions.

Cardioprotective and Vasoprotective Effects of Corticotropin-Releasing Hormone and Urocortins: Receptors and Signaling

2021 ◽  
pp. 107424842098530
Author(s):  
Sergey V. Popov ◽  
Ekaterina S. Prokudina ◽  
Alexander V. Mukhomedzyanov ◽  
Natalia V. Naryzhnaya ◽  
Huijie Ma ◽  
...  
Keyword(s):  
Mitochondrial Permeability Transition ◽  
Vascular Endothelial Cells ◽  
Isolated Heart ◽  
Cardiac Contractility ◽  
Permeability Transition Pore ◽  
Chronic Administration ◽  
Permeability Transition ◽  
Janus Kinase ◽  
Corticotropin Releasing Hormone ◽  
Releasing Hormone

Despite the recent progress in research and therapy, cardiovascular diseases are still the most common cause of death worldwide, thus new approaches are still needed. The aim of this review is to highlight the cardioprotective potential of urocortins and corticotropin-releasing hormone (CRH) and their signaling. It has been documented that urocortins and CRH reduce ischemic and reperfusion (I/R) injury, prevent reperfusion ventricular tachycardia and fibrillation, and improve cardiac contractility during reperfusion. Urocortin-induced increase in cardiac tolerance to I/R depends mainly on the activation of corticotropin-releasing hormone receptor-2 (CRHR2) and its downstream pathways including tyrosine kinase Src, protein kinase A and C (PKA, PKCε) and extracellular signal-regulated kinase (ERK1/2). It was discussed the possibility of the involvement of interleukin-6, Janus kinase-2 and signal transducer and activator of transcription 3 (STAT3) and microRNAs in the cardioprotective effect of urocortins. Additionally, phospholipase-A2 inhibition, mitochondrial permeability transition pore (MPT-pore) blockade and suppression of apoptosis are involved in urocortin-elicited cardioprotection. Chronic administration of urocortin-2 prevents the development of postinfarction cardiac remodeling. Urocortin possesses vasoprotective and vasodilator effect; the former is mediated by PKC activation and prevents an impairment of endothelium-dependent coronary vasodilation after I/R in the isolated heart, while the latter includes both cAMP and cGMP signaling and its downstream targets. As CRHR2 is expressed by both cardiomyocytes and vascular endothelial cells. Urocortins mediate both endothelium-dependent and -independent relaxation of coronary arteries.

scholarly journals Astaxanthin Inhibits Mitochondrial Permeability Transition Pore Opening in Rat Heart Mitochondria

Antioxidants ◽  
2019 ◽  
Vol 8 (12) ◽  
pp. 576 ◽  
Author(s):  
Yulia Baburina ◽  
Roman Krestinin ◽  
Irina Odinokova ◽  
Linda Sotnikova ◽  
Alexey Kruglov ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Rat Heart ◽  
Mitochondrial Permeability Transition Pore ◽  
Mitochondrial Permeability Transition ◽  
Permeability Transition Pore ◽  
Permeability Transition ◽  
Heart Mitochondria ◽  
Inner Mitochondrial Membrane ◽  
Mitochondrial Permeability ◽  
Rat Heart Mitochondria

The mitochondrion is the main organelle of oxidative stress in cells. Increased permeability of the inner mitochondrial membrane is a key phenomenon in cell death. Changes in membrane permeability result from the opening of the mitochondrial permeability transition pore (mPTP), a large-conductance channel that forms after the overload of mitochondria with Ca2+ or in response to oxidative stress. The ketocarotenoid astaxanthin (AST) is a potent antioxidant that is capable of maintaining the integrity of mitochondria by preventing oxidative stress. In the present work, the effect of AST on the functioning of mPTP was studied. It was found that AST was able to inhibit the opening of mPTP, slowing down the swelling of mitochondria by both direct addition to mitochondria and administration. AST treatment changed the level of mPTP regulatory proteins in isolated rat heart mitochondria. Consequently, AST can protect mitochondria from changes in the induced permeability of the inner membrane. AST inhibited serine/threonine protein kinase B (Akt)/cAMP-responsive element-binding protein (CREB) signaling pathways in mitochondria, which led to the prevention of mPTP opening. Since AST improves the resistance of rat heart mitochondria to Ca2+-dependent stress, it can be assumed that after further studies, this antioxidant will be considered an effective tool for improving the functioning of the heart muscle in general under normal and medical conditions.

scholarly journals The Functions of Mitochondrial 2′,3′-Cyclic Nucleotide-3′-Phosphodiesterase and Prospects for Its Future

2020 ◽  
Vol 21 (9) ◽  
pp. 3217 ◽  
Author(s):  
Krestinina Olga ◽  
Baburina Yulia ◽  
Papadopoulos Vassilios
Keyword(s):  
Cyclic Nucleotide ◽  
Mitochondrial Permeability Transition Pore ◽  
Mitochondrial Permeability Transition ◽  
Permeability Transition Pore ◽  
Permeability Transition ◽  
Pathological Conditions ◽  
Phosphodiester Hydrolysis ◽  
Apoptosis And Necrosis ◽  
Hydrolysis Of

2′,3′-cyclic nucleotide-3′-phosphodiesterase (CNPase) is a myelin-associated enzyme that catalyzes the phosphodiester hydrolysis of 2’,3’-cyclic nucleotides to 2’-nucleotides. However, its presence is also found in unmyelinated cells and other cellular structures. Understanding of its specific physiological functions, particularly in unmyelinated cells, is still incomplete. This review concentrates on the role of mitochondrial CNPase (mtCNPase), independent of myelin. mtCNPase is able to regulate the functioning of the mitochondrial permeability transition pore (mPTP), and thus is involved in the mechanisms of cell death, both apoptosis and necrosis. Its participation in the development of various diseases and pathological conditions, such as aging, heart disease and alcohol dependence, is also reviewed. As such, mtCNPase can be considered as a potential target for the development of therapeutic strategies in the treatment of mitochondria-related diseases.

scholarly journals Isoproterenol-Induced Permeability Transition Pore-Related Dysfunction of Heart Mitochondria Is Attenuated by Astaxanthin

Biomedicines ◽  
2020 ◽  
Vol 8 (10) ◽  
pp. 437
Author(s):  
Roman Krestinin ◽  
Yulia Baburina ◽  
Irina Odinokova ◽  
Alexey Kruglov ◽  
Irina Fadeeva ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Rat Heart ◽  
Mitochondrial Permeability Transition ◽  
Permeability Transition Pore ◽  
Permeability Transition ◽  
Antioxidant Defense System ◽  
Heart Mitochondria ◽  
Main Function ◽  
Retention Capacity ◽  
Rat Heart Mitochondria

Mitochondria are key organelles of the cell because their main function is the capture of energy-rich substrates from the cytoplasm and oxidative cleavage with the generation of carbon dioxide and water, processes that are coupled with the synthesis of ATP. Mitochondria are subject to oxidative stress through the formation of the mitochondrial permeability transition pore (mPTP). Various antioxidants are used to reduce damage caused by oxidative stress and to improve the protection of the antioxidant system. Astaxanthin (AST) is considered to be a dietary antioxidant, which is able to reduce oxidative stress and enhance the antioxidant defense system. In the present investigation, the effect of AST on the functional state of rat heart mitochondria impaired by isoproterenol (ISO) under mPTP functioning was examined. It was found that AST raised mitochondrial respiration, the Ca2+ retention capacity (CRC), and the rate of TPP+ influx in rat heart mitochondria (RHM) isolated from ISO-injected rats. However, the level of reactive oxygen species (ROS) production increased. In addition, the concentrations of cardiolipin (CL), Mn-SOD2, and the proteins regulating mPTP rose after the injection of ISO in RHM pretreated with AST. Based on the data obtained, we suggest that AST has a protective effect in rat heart mitochondria.

scholarly journals The Role of Mitochondrial Functional Proteins in ROS Production in Ischemic Heart Diseases

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Haifeng Pei ◽  
Yi Yang ◽  
Heng Zhao ◽  
Xiuchuan Li ◽  
Dachun Yang ◽  
...  
Keyword(s):  
Cell Injury ◽  
Mitochondrial Permeability Transition ◽  
Heart Diseases ◽  
Coronary Vessels ◽  
Permeability Transition Pore ◽  
Permeability Transition ◽  
Ischemic Heart ◽  
Ros Production ◽  
Mitochondrial Dynamic ◽  
Ischemic Heart Diseases

Ischemic heart diseases (IHD) have become the leading cause of death around the world, killing more than 7 million people annually. In IHD, the blockage of coronary vessels will cause irreversible cell injury and even death. As the “powerhouse” and “apoptosis center” in cardiomyocytes, mitochondria play critical roles in IHD. Ischemia insult can reduce myocardial ATP content, resulting in energy stress and overproduction of reactive oxygen species (ROS). Thus, mitochondrial abnormality has been identified as a hallmark of multiple cardiovascular disorders. To date, many studies have suggested that these mitochondrial proteins, such as electron transport chain (ETC) complexes, uncoupling proteins (UCPs), mitochondrial dynamic proteins, translocases of outer membrane (Tom) complex, and mitochondrial permeability transition pore (MPTP), can directly or indirectly influence mitochondria-originated ROS production, consequently determining the degree of mitochondrial dysfunction and myocardial impairment. Here, the focus of this review is to summarize the present understanding of the relationship between some mitochondrial functional proteins and ROS production in IHD.

scholarly journals Effects of pinacidil and calcium on succinate-energized rat heart mitochondria in the presence of rotenone

2019 ◽  
Vol 487 (4) ◽  
pp. 460-464
Author(s):  
S. M. Korotkov ◽  
I. V. Brailovskaya ◽  
V. P. Nesterov ◽  
S. I. Soroko
Keyword(s):  
Rat Heart ◽  
Mitochondrial Permeability Transition Pore ◽  
Mitochondrial Permeability Transition ◽  
Ischemia Reperfusion ◽  
Permeability Transition Pore ◽  
Permeability Transition ◽  
Heart Mitochondria ◽  
Inner Membrane ◽  
Muscle Ischemia ◽  
Rat Heart Mitochondria

The effect of pinacidil was studied on calcium-loaded rat heart mitochondria (RHM) in the presence of succinate and rotenone. In experiments with pinacidil, the swelling of these mitochondria increased in media with NH4NO3 or K‑acetate, but the inner membrane potential DΨmito and state 3 or 2,4-dinitrophenol-uncoupled respiration of these organelles were decreased due to opening of the mitochondrial permeability transition pore in the inner membrane. These effects were inhibited by cyclosporin A and ADP. It was concluded that the protective effect of pinacidil in the cardiac muscle ischemia/reperfusion may be associated with stimulation mitochondrial swelling and a decrease in RHM calcium overload resulted in a decrease in DΨmito due to the soft uncoupling pinacidil effect.

scholarly journals Molecular Mechanisms of Melatonin-Mediated Cell Protection and Signaling in Health and Disease

Pharmaceutics ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 129
Author(s):  
Dalia M. Kopustinskiene ◽  
Jurga Bernatoniene
Keyword(s):  
Mitochondrial Membrane ◽  
Molecular Mechanisms ◽  
Mitochondrial Permeability Transition ◽  
Permeability Transition Pore ◽  
Permeability Transition ◽  
Membrane Phospholipids ◽  
Cell Protection ◽  
Cytochrome C Release ◽  
Pathological Conditions ◽  
Beneficial Action

Melatonin, an endogenously synthesized indolamine, is a powerful antioxidant exerting beneficial action in many pathological conditions. Melatonin protects from oxidative stress in ischemic/reperfusion injury, neurodegenerative diseases, and aging, decreases inflammation, modulates the immune system, inhibits proliferation, counteracts the Warburg effect, and promotes apoptosis in various cancer models. Melatonin stimulates antioxidant enzymes in the cells, protects mitochondrial membrane phospholipids, especially cardiolipin, from oxidation thus preserving integrity of the membranes, affects mitochondrial membrane potential, stimulates activity of respiratory chain enzymes, and decreases the opening of mitochondrial permeability transition pore and cytochrome c release. This review will focus on the molecular mechanisms of melatonin effects in the cells during normal and pathological conditions and possible melatonin clinical applications.

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