scholarly journals Recent Advances in Pharmacological and Non-Pharmacological Strategies of Cardioprotection

2019 ◽  
Vol 20 (16) ◽  
pp. 4002 ◽  
Author(s):  
Afonso Caricati-Neto ◽  
Paolo Ruggero Errante ◽  
Francisco Sandro Menezes-Rodrigues
Keyword(s):  
Intracellular Signaling ◽  
Molecular Mechanisms ◽  
Heart Diseases ◽  
Cardiac Cells ◽  
Ischemia And Reperfusion ◽  
Protective Response ◽  
Pharmacological Agents ◽  
Ischemic Heart Diseases ◽  
Intracellular Signaling Pathways ◽  
Recent Advances

Ischemic heart diseases (IHD) are the leading cause of death worldwide. Although the principal form of treatment of IHD is myocardial reperfusion, the recovery of coronary blood flow after ischemia can cause severe and fatal cardiac dysfunctions, mainly due to the abrupt entry of oxygen and ionic deregulation in cardiac cells. The ability of these cells to protect themselves against injury including ischemia and reperfusion (I/R), has been termed “cardioprotection”. This protective response can be stimulated by pharmacological agents (adenosine, catecholamines and others) and non-pharmacological procedures (conditioning, hypoxia and others). Several intracellular signaling pathways mediated by chemical messengers (enzymes, protein kinases, transcription factors and others) and cytoplasmic organelles (mitochondria, sarcoplasmic reticulum, nucleus and sarcolemma) are involved in cardioprotective responses. Therefore, advancement in understanding the cellular and molecular mechanisms involved in the cardioprotective response can lead to the development of new pharmacological and non-pharmacological strategies for cardioprotection, thus contributing to increasing the efficacy of IHD treatment. In this work, we analyze the recent advances in pharmacological and non-pharmacological strategies of cardioprotection.

scholarly journals Antioxidants in Sport Sarcopenia

Nutrients ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2869
Author(s):  
Maria Michela Cesare ◽  
Francesca Felice ◽  
Veronica Santini ◽  
Rossella Di Stefano
Keyword(s):  
Muscle Mass ◽  
Intracellular Signaling ◽  
Molecular Mechanisms ◽  
Physiological State ◽  
Experimental Models ◽  
Adaptive Responses ◽  
Master Athletes ◽  
Intracellular Signaling Pathways ◽  
Endogenous Protection ◽  
New Strategies

The decline of skeletal muscle mass and strength that leads to sarcopenia is a pathology that might represent an emergency healthcare issue in future years. Decreased muscle mass is also a condition that mainly affects master athletes involved in endurance physical activities. Skeletal muscles respond to exercise by reshaping the biochemical, morphological, and physiological state of myofibrils. Adaptive responses involve the activation of intracellular signaling pathways and genetic reprogramming, causing alterations in contractile properties, metabolic status, and muscle mass. One of the mechanisms leading to sarcopenia is an increase in reactive oxygen and nitrogen species levels and a reduction in enzymatic antioxidant protection. The present review shows the recent experimental models of sarcopenia that explore molecular mechanisms. Furthermore, the clinical aspect of sport sarcopenia will be highlighted, and new strategies based on nutritional supplements, which may contribute to reducing indices of oxidative stress by reinforcing natural endogenous protection, will be suggested.

scholarly journals Role of Calcium and EPAC in Norepinephrine-Induced Ghrelin Secretion

Endocrinology ◽  
2014 ◽  
Vol 155 (1) ◽  
pp. 98-107 ◽  
Author(s):  
Bharath K. Mani ◽  
Jen-Chieh Chuang ◽  
Lilja Kjalarsdottir ◽  
Ichiro Sakata ◽  
Angela K. Walker ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Intracellular Signaling ◽  
Endocrine Cells ◽  
Molecular Mechanisms ◽  
Phosphodiesterase Inhibitor ◽  
Intracellular Signaling Pathways ◽  
Ghrelin Secretion ◽  
Kinase A

Ghrelin is an orexigenic hormone secreted principally from a distinct population of gastric endocrine cells. Molecular mechanisms regulating ghrelin secretion are mostly unknown. Recently, norepinephrine (NE) was shown to enhance ghrelin release by binding to β1-adrenergic receptors on ghrelin cells. Here, we use an immortalized stomach-derived ghrelin cell line to further characterize the intracellular signaling pathways involved in NE-induced ghrelin secretion, with a focus on the roles of Ca2+ and cAMP. Several voltage-gated Ca2+ channel (VGCC) family members were found by quantitative PCR to be expressed by ghrelin cells. Nifedipine, a selective L-type VGCC blocker, suppressed both basal and NE-stimulated ghrelin secretion. NE induced elevation of cytosolic Ca2+ levels both in the presence and absence of extracellular Ca2+. Ca2+-sensing synaptotagmins Syt7 and Syt9 were also highly expressed in ghrelin cell lines, suggesting that they too help mediate ghrelin secretion. Raising cAMP with the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine also stimulated ghrelin secretion, although such a cAMP-mediated effect likely does not involve protein kinase A, given the absence of a modulatory response to a highly selective protein kinase A inhibitor. However, pharmacological inhibition of another target of cAMP, exchange protein-activated by cAMP (EPAC), did attenuate both basal and NE-induced ghrelin secretion, whereas an EPAC agonist enhanced basal ghrelin secretion. We conclude that constitutive ghrelin secretion is primarily regulated by Ca2+ influx through L-type VGCCs and that NE stimulates ghrelin secretion predominantly through release of intracellular Ca2+. Furthermore, cAMP and its downstream activation of EPAC are required for the normal ghrelin secretory response to NE.

scholarly journals An Update of Molecular Basis of Telomere Biology Diseases

2021 ◽  
Author(s):  
Eleonora Vertecchi ◽  
Angela Iuzzolino ◽  
Erica Salvati
Keyword(s):  
Intracellular Signaling ◽  
Genome Stability ◽  
Molecular Mechanisms ◽  
Recent Literature ◽  
Telomere Attrition ◽  
Intracellular Signaling Pathways ◽  
Cycle Arrest ◽  
Damage Repair ◽  
Human Disorders ◽  
Telomere Biology

Telomeres are crucial structures that preserve genome stability. Their progressive erosion over rounds of DNA duplication determines senescence of cells and organisms. In a classic view, telomere biology impinges on intracellular signaling pathways regulating DNA damage repair and cell cycle arrest, but new roles of telomeric proteins and transcripts emerge from recent literature. Telomere biology diseases are human disorders associated to telomere attrition. This review wants to overview the recent findings in the field of telomere’s metabolism and to deepen molecular mechanisms of inherited and acquired telomeropathies, explaining new critical connections between telomeric factors and disease pathogenesis

scholarly journals Molecular and genetic mechanisms of heterotopic ossification

2020 ◽  
pp. 102-110
Author(s):  
И.А. Степанов ◽  
В.А. Белобородов ◽  
М.А. Шамеева
Keyword(s):  
Heterotopic Ossification ◽  
Intracellular Signaling ◽  
Molecular Mechanisms ◽  
Soft Tissues ◽  
Experimental Studies ◽  
Therapeutic Approaches ◽  
Intracellular Signaling Pathways ◽  
Treatment And Prevention ◽  
Genetic Mechanisms ◽  
Molecular Therapeutic

В обзоре освещены данные современной литературы, посвященные изучению молекулярно-генетических механизмов гетеротопической оссификации (ГО). ГО представляет собой процесс образования пластинчатой кости в мягких тканях, не имеющих остеогенных свойств. В патогенезе формирования очагов ГО важнейшую роль играет ряд внутриклеточных сигнальных путей, ответственных за направление дифференцировки мезенхимальных стволовых клеток по пути остеогенеза. Представлен анализ экспериментальных исследований, изучающих молекулярные механизмы ГО. Авторами изложены современные данные о молекулярных терапевтических подходах к лечению и профилактике ГО. Обозначены актуальные, остающиеся нерешенными вопросы, что диктует необходимость проведения дальнейших экспериментальных и клинических исследований проблемы гетеротопической оссификации. This review addressed molecular and genetic mechanisms of heterotopic ossification (HO). HO is a process of lamellar bone formation in soft tissues lacking osteogenic properties. Several intracellular signaling pathways for differentiation of mesenchymal stem cells along with the osteogenesis pathway play an important role in the pathogenesis of HO formation. This review analyzed experimental studies of HO molecular mechanisms. The authors presented state-of-the-art information about molecular therapeutic approaches in HO treatment and prevention and identified relevant but still unresolved issues, which warrant further experimental and clinical studies.

Cardiac ATP-sensitive K+ channels: regulation by intracellular nucleotides and K+ channel-opening drugs

1995 ◽  
Vol 269 (3) ◽  
pp. C525-C545 ◽  
Author(s):  
A. Terzic ◽  
A. Jahangir ◽  
Y. Kurachi
Keyword(s):  
Katp Channel ◽  
Molecular Mechanisms ◽  
Enzymatic Reaction ◽  
Katp Channels ◽  
Cardiac Cells ◽  
K Channel ◽  
Channel Activity ◽  
Pharmacological Agents ◽  
Channel Opening ◽  
Main Regulator

ATP-sensitive K+ (KATP) channels are present at high density in membranes of cardiac cells where they regulate cardiac function during cellular metabolic impairment. KATP channels have been implicated in the shortening of the action potential duration and the cellular loss of K+ that occurs during metabolic inhibition. KATP channels have been associated with the cardioprotective mechanism of ischemia-related preconditioning. Intracellular ATP (ATPi) is the main regulator of KATP channels. ATPi has two functions: 1) to close the channel (ligand function) and 2) in the presence of Mg2+, to maintain the activity of KATP channels (presumably through an enzymatic reaction). KATP channel activity is modulated by intracellular nucleoside diphosphates that antagonize the ATPi-induced inhibition of channel opening or induce KATP channels to open. How nucleotides will affect KATP channels depends on the state of the channel. K+ channel-opening drugs are pharmacological agents that enhance KATP channel activity through different mechanisms and have great potential in the management of cardiovascular conditions. KATP channel activity is also modulated by neurohormones. Adenosine, through the activation of a GTP-binding protein, antagonizes the ATPi-induced channel closure. Understanding the molecular mechanisms that underlie KATP channel regulation should prove essential to further define the function of KATP channels and to elucidate the pharmacological regulation of this channel protein. Since the molecular structure of the KATP channel has now become available, it is anticipated that major progress in the KATP channel field will be achieved.

scholarly journals FSH directly regulates chondrocyte dedifferentiation and cartilage development

2020 ◽  
Author(s):  
Yan Wang ◽  
Mengqi Zhang ◽  
Zhikun Huan ◽  
Shanshan Shao ◽  
Xiujuan Zhang ◽  
...  
Keyword(s):  
Intracellular Signaling ◽  
Molecular Mechanisms ◽  
Cell Loss ◽  
Type Ii Collagen ◽  
Cartilage Destruction ◽  
Intracellular Signaling Pathways ◽  
Cartilage Development ◽  
Cytoskeleton Reorganization ◽  
Important Regulator ◽  
And Cartilage

Previous studies suggest that postmenopausal osteoarthritis is linked to a decrease in estrogen levels. However, whether follicle-stimulating hormone (FSH), the upstream hormone of estrogen, affects cartilage destruction and thus contributes to the onset of osteoarthritis has never been explored. To evaluate the potential involvement of FSH in joint degeneration and to identify the molecular mechanisms through which FSH influences chondrocytes, mouse cartilage chondrocytes and the ATDC5 chondrocyte cell line were treated with FSH and inhibitors of intracellular signaling pathways. We observed that FSH induces chondrocyte dedifferentiation by decreasing type II collagen (Coll-II) synthesis. Chondrocyte cytoskeleton reorganization was also observed after FSH treatment. The FSH-induced decrease in Coll-II was rescued by ERK-1/2 inhibition but aggravated by p38 inhibition. In addition, knocking down the FSH receptor (Fshr) by using Fshr siRNA abolished chondrocyte dedifferentiation, as indicated by the increased expression of Coll-II. Inhibition of the protein Gαi by pertussis toxin (PTX) also restored FSH-inhibited Coll-II, suggesting that Gαi is downstream of FSHR in chondrocyte dedifferentiation. FSHβ antibody blockade prevented cartilage destruction and cell loss in mice. Moreover, decreased Coll-II staining due to the progression of aging could be rescued by blocking FSH. Thus, we suggest that high circulating FSH, independent of estrogen, is an important regulator in chondrocyte dedifferentiation and cartilage destruction.

The Mechanisms Behind the Biological Activity of Flavonoids

2019 ◽  
Vol 26 (39) ◽  
pp. 6976-6990 ◽  
Author(s):  
Ana María González-Paramás ◽  
Begoña Ayuda-Durán ◽  
Sofía Martínez ◽  
Susana González-Manzano ◽  
Celestino Santos-Buelga
Keyword(s):  
Gene Expression ◽  
Biological Activity ◽  
Phenolic Compounds ◽  
Intracellular Signaling ◽  
Molecular Mechanisms ◽  
Radical Scavenging ◽  
Model Organism ◽  
Stress Theory ◽  
Radical Scavenging Properties

: Flavonoids are phenolic compounds widely distributed in the human diet. Their intake has been associated with a decreased risk of different diseases such as cancer, immune dysfunction or coronary heart disease. However, the knowledge about the mechanisms behind their in vivo activity is limited and still under discussion. For years, their bioactivity was associated with the direct antioxidant and radical scavenging properties of phenolic compounds, but nowadays this assumption is unlikely to explain their putative health effects, or at least to be the only explanation for them. New hypotheses about possible mechanisms have been postulated, including the influence of the interaction of polyphenols and gut microbiota and also the possibility that flavonoids or their metabolites could modify gene expression or act as potential modulators of intracellular signaling cascades. This paper reviews all these topics, from the classical view as antioxidants in the context of the Oxidative Stress theory to the most recent tendencies related with the modulation of redox signaling pathways, modification of gene expression or interactions with the intestinal microbiota. The use of C. elegans as a model organism for the study of the molecular mechanisms involved in biological activity of flavonoids is also discussed.

Recent Advances in Rational Diagnosis and Treatment of Normal Pressure Hydrocephalus: A Critical Appraisal on Novel Diagnostic, Therapy Monitoring and Treatment Modalities

2019 ◽  
Vol 20 (10) ◽  
pp. 1041-1057 ◽  
Author(s):  
Lei Zhang ◽  
Zahid Hussain ◽  
Zhuanqin Ren
Keyword(s):  
Cerebrospinal Fluid ◽  
Normal Pressure Hydrocephalus ◽  
Critical Appraisal ◽  
Therapy Monitoring ◽  
Normal Pressure ◽  
Treatment Modalities ◽  
Pharmacological Agents ◽  
Recent Advances ◽  
Rational Diagnosis ◽  
Neuroimaging Techniques

Background:Normal pressure hydrocephalus (NPH) is a critical brain disorder in which excess Cerebrospinal Fluid (CSF) is accumulated in the brain’s ventricles causing damage or disruption of the brain tissues. Amongst various signs and symptoms, difficulty in walking, slurred speech, impaired decision making and critical thinking, and loss of bladder and bowl control are considered the hallmark features of NPH.Objective:The current review was aimed to present a comprehensive overview and critical appraisal of majorly employed neuroimaging techniques for rational diagnosis and effective monitoring of the effectiveness of the employed therapeutic intervention for NPH. Moreover, a critical overview of recent developments and utilization of pharmacological agents for the treatment of hydrocephalus has also been appraised.Results:Considering the complications associated with the shunt-based surgical operations, consistent monitoring of shunting via neuroimaging techniques hold greater clinical significance. Despite having extensive applicability of MRI and CT scan, these conventional neuroimaging techniques are associated with misdiagnosis or several health risks to patients. Recent advances in MRI (i.e., Sagittal-MRI, coronal-MRI, Time-SLIP (time-spatial-labeling-inversion-pulse), PC-MRI and diffusion-tensor-imaging (DTI)) have shown promising applicability in the diagnosis of NPH. Having associated with several adverse effects with surgical interventions, non-invasive approaches (pharmacological agents) have earned greater interest of scientists, medical professional, and healthcare providers. Amongst pharmacological agents, diuretics, isosorbide, osmotic agents, carbonic anhydrase inhibitors, glucocorticoids, NSAIDs, digoxin, and gold-198 have been employed for the management of NPH and prevention of secondary sensory/intellectual complications.Conclusion:Employment of rational diagnostic tool and therapeutic modalities avoids misleading diagnosis and sophisticated management of hydrocephalus by efficient reduction of Cerebrospinal Fluid (CSF) production, reduction of fibrotic and inflammatory cascades secondary to meningitis and hemorrhage, and protection of brain from further deterioration.

Sign in / Sign up

Export Citation Format

Share Document