scholarly journals TASK-1 (KCNK3) channels in the lung: from cell biology to clinical implications

2017 ◽  
Vol 50 (5) ◽  
pp. 1700754 ◽  
Author(s):  
Andrea Olschewski ◽  
Emma L. Veale ◽  
Bence M. Nagy ◽  
Chandran Nagaraj ◽  
Grazyna Kwapiszewska ◽  
...  
Keyword(s):  
Pulmonary Circulation ◽  
Cell Biology ◽  
Unsaturated Fatty Acids ◽  
Excitable Cells ◽  
Intracellular Signalling Pathways ◽  
Current State ◽  
Health And Disease ◽  
Pulmonary Arterial ◽  
Pore Domain

TWIK-related acid-sensitive potassium channel 1 (TASK-1 encoded by KCNK3) belongs to the family of two-pore domain potassium channels. This gene subfamily is constitutively active at physiological resting membrane potentials in excitable cells, including smooth muscle cells, and has been particularly linked to the human pulmonary circulation. TASK-1 channels are sensitive to a wide array of physiological and pharmacological mediators that affect their activity such as unsaturated fatty acids, extracellular pH, hypoxia, anaesthetics and intracellular signalling pathways. Recent studies show that modulation of TASK-1 channels, either directly or indirectly by targeting their regulatory mechanisms, has the potential to control pulmonary arterial tone in humans. Furthermore, mutations in KCNK3 have been identified as a rare cause of both familial and idiopathic pulmonary arterial hypertension. This review summarises our current state of knowledge of the functional role of TASK-1 channels in the pulmonary circulation in health and disease, with special emphasis on current advancements in the field.

scholarly journals 55th Bowditch Lecture: Effects of chronic hypoxia on the pulmonary circulation: Role of HIF-1

2012 ◽  
Vol 113 (9) ◽  
pp. 1343-1352 ◽  
Author(s):  
Larissa A. Shimoda
Keyword(s):  
Pulmonary Hypertension ◽  
Pulmonary Circulation ◽  
Vascular Remodeling ◽  
Chronic Hypoxia ◽  
Critical Role ◽  
Hypoxia Inducible Factor ◽  
Hypoxia Inducible Factor 1 ◽  
Pulmonary Arterial ◽  
Expression And Activity

When exposed to chronic hypoxia (CH), the pulmonary circulation responds with enhanced contraction and vascular remodeling, resulting in elevated pulmonary arterial pressures. Our work has identified CH-induced alterations in the expression and activity of several ion channels and transporters in pulmonary vascular smooth muscle that contribute to the development of hypoxic pulmonary hypertension and uncovered a critical role for the transcription factor hypoxia-inducible factor-1 (HIF-1) in mediating these responses. Current work is focused on the regulation of HIF in the chronically hypoxic lung and evaluation of the potential for pharmacological inhibitors of HIF to prevent, reverse, or slow the progression of pulmonary hypertension.

scholarly journals HDL Cholesterol as a Marker of Disease Severity and Prognosis in Patients with Pulmonary Arterial Hypertension

2019 ◽  
Vol 20 (14) ◽  
pp. 3514 ◽  
Author(s):  
Kamil Jonas ◽  
Grzegorz Kopeć
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Vascular Endothelium ◽  
Pulmonary Circulation ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Systemic Circulation ◽  
Pulmonary Arterial ◽  
The Impact

The impact of high-density lipoprotein (HDL) cholesterol on the development of atherosclerosis and diseases of systemic circulation has been well documented both in experimental and registry studies. Recent discoveries in pulmonary arterial hypertension (PAH) revealed a significant impact of HDL on pulmonary artery vasoreactivity and patients’ prognosis. The vasoprotective activity of HDL primarily involves vascular endothelium that also plays a central role in pulmonary arterial hypertension (PAH) pathobiology. However, the exact mechanism in which this lipoprotein fraction exerts its effect in pulmonary circulation is still under investigation. This paper reviews potential vasoprotective mechanisms of HDL in pulmonary circulation and presents current clinical reports on the role of HDL in PAH patients.

scholarly journals Monitoring of compound resting membrane potentials of cell cultures with ratiometric genetically encoded voltage indicators

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Philipp Rühl ◽  
Johanna M. Langner ◽  
Jasmin Reidel ◽  
Roland Schönherr ◽  
Toshinori Hoshi ◽  
...  
Keyword(s):  
Cell Cycle Progression ◽  
Ectopic Expression ◽  
Resting Membrane Potential ◽  
Excitable Cells ◽  
Cycle Progression ◽  
Cell Groups ◽  
Health And Disease ◽  
Term Monitoring

AbstractThe cellular resting membrane potential (Vm) not only determines electrical responsiveness of excitable cells but also plays pivotal roles in non-excitable cells, mediating membrane transport, cell-cycle progression, and tumorigenesis. Studying these processes requires estimation of Vm, ideally over long periods of time. Here, we introduce two ratiometric genetically encoded Vm indicators, rArc and rASAP, and imaging and analysis procedures for measuring differences in average resting Vm between cell groups. We investigated the influence of ectopic expression of K+ channels and their disease-causing mutations involved in Andersen-Tawil (Kir2.1) and Temple-Baraitser (KV10.1) syndrome on median resting Vm of HEK293T cells. Real-time long-term monitoring of Vm changes allowed to estimate a 40–50 min latency from induction of transcription to functional Kir2.1 channels in HEK293T cells. The presented methodology is readily implemented with standard fluorescence microscopes and offers deeper insights into the role of the resting Vm in health and disease.

scholarly journals The CLU-files: disentanglement of a mystery

2016 ◽  
Vol 7 (1) ◽  
pp. 1-15 ◽  
Author(s):  
Philipp Rohne ◽  
Hans Prochnow ◽  
Claudia Koch-Brandt
Keyword(s):  
Molecular Chaperone ◽  
Cell Biology ◽  
Protein S ◽  
Subcellular Location ◽  
Current State ◽  
Apolipoprotein J ◽  
Health And Disease ◽  
Molecular Cell Biology ◽  
And Function

AbstractThe multifaceted protein clusterin (CLU) has been challenging researchers for more than 35 years. The characterization of CLU as a molecular chaperone was one of the major breakthroughs in CLU research. Today, secretory clusterin (sCLU), also known as apolipoprotein J (apoJ), is considered one of the most important extracellular chaperones ever found. It is involved in a broad range of physiological and pathophysiological functions, where it exerts a cytoprotective role. Descriptions of various forms of intracellular CLU have led to further and even contradictory functions. To untangle the current state of knowledge of CLU, this review will combine old views in the field, with new discoveries to highlight the nature and function of this fascinating protein(s). In this review, we further describe the expression and subcellular location of various CLU forms. Moreover, we discuss recent insights into the structure of CLU and assess how structural properties as well as the redox environment determine the chaperone activity of CLU. Eventually, the review connects the biochemistry and molecular cell biology of CLU with medical aspects, to formulate a hypothesis of a CLU function in health and disease.

scholarly journals The Role of Proteases and Serpin Protease Inhibitors in β-Cell Biology and Diabetes

Biomolecules ◽  
2022 ◽  
Vol 12 (1) ◽  
pp. 67
Author(s):  
Yury Kryvalap ◽  
Jan Czyzyk
Keyword(s):  
Protease Inhibitors ◽  
Protease Activity ◽  
Cell Biology ◽  
Cysteine Proteases ◽  
Health Maintenance ◽  
Clade B ◽  
New Strategy ◽  
Health And Disease ◽  
Pancreatic Islet Biology

Regulation of the equilibrium between proteases and their inhibitors is fundamental to health maintenance. Consequently, developing a means of targeting protease activity to promote tissue regeneration and inhibit inflammation may offer a new strategy in therapy development for diabetes and other diseases. Specifically, recent efforts have focused on serine protease inhibitors, known as serpins, as potential therapeutic targets. The serpin protein family comprises a broad range of protease inhibitors, which are categorized into 16 clades that are all extracellular, with the exception of Clade B, which controls mostly intracellular proteases, including both serine- and papain-like cysteine proteases. This review discusses the most salient, and sometimes opposing, views that either inhibition or augmentation of protease activity can bring about positive outcomes in pancreatic islet biology and inflammation. These potential discrepancies can be reconciled at the molecular level as specific proteases and serpins regulate distinct signaling pathways, thereby playing equally distinct roles in health and disease development.

scholarly journals Beyond Thrombosis: the Role of Platelets in Pulmonary Hypertension

2020 ◽  
Vol 2 (4) ◽  
pp. 243-271
Author(s):  
Salina Nicoleau ◽  
Beata Wojciak-Stothard
Keyword(s):  
Pulmonary Hypertension ◽  
Pulmonary Arterial Pressure ◽  
Right Heart Failure ◽  
Inflammatory Cells ◽  
The Past ◽  
Current State ◽  
Wide Range ◽  
Pulmonary Arterial

Pulmonary Hypertension (PH) is a multifactorial and lethal disease, characterised by elevated pulmonary arterial pressure and progressive right heart failure. PH pathobiology rests on four pillars: vascular remodelling, vasoconstriction, inflammation and thrombosis. While vascular and inflammatory cells have been the focus of PH research over the past decades, platelets have received relatively less attention, despite their associations with key pathophysiological processes of the disease. Platelets contain a wide range of vasoactive, inflammatory and pro-thrombotic mediators, likely to promote PH development and progression. There is currently no cure for PH, and platelet-associated pathways may help identify new therapeutic strategies. This review summarises available evidence on the role of platelets in different forms of PH, and comments on the current state of platelet-targeting therapies. It also describes the latest advances in the in vitro technologies that enable exploration of platelet function under dynamic and physiologically relevant conditions. Doi: 10.28991/SciMedJ-2020-0204-7 Full Text: PDF

scholarly journals The biochemical basis of disease

2018 ◽  
Vol 62 (5) ◽  
pp. 619-642 ◽  
Author(s):  
Alastair J. Barr
Keyword(s):  
Liver Disease ◽  
Global Health ◽  
Cell Biology ◽  
Biochemical Basis ◽  
New Developments ◽  
Biochemical Pathways ◽  
Causes Of Disease ◽  
Health And Disease ◽  
Insight Into

This article gives the reader an insight into the role of biochemistry in some of the current global health and disease problems. It surveys the biochemical causes of disease in an accessible and succinct form while also bringing in aspects of pharmacology, cell biology, pathology and physiology which are closely aligned with biochemistry. The discussion of the selected diseases highlights exciting new developments and illuminates key biochemical pathways and commonalities. The article includes coverage of diabetes, atherosclerosis, cancer, microorganisms and disease, nutrition, liver disease and Alzheimer’s disease, but does not attempt to be comprehensive in its coverage of disease, since this is beyond its remit and scope. Consequently there are many fascinating biochemical aspects of diseases, both common and rare, that are not addressed here that can be explored in the further reading cited. Techniques and biochemical procedures for studying disease are not covered in detail here, but these can be found readily in a range of biochemical methods sources.

scholarly journals The Role of β-Arrestins in Regulating Stem Cell Phenotypes in Normal and Tumorigenic Cells

2020 ◽  
Vol 21 (23) ◽  
pp. 9310
Author(s):  
Georgios Kallifatidis ◽  
Kenza Mamouni ◽  
Bal L. Lokeshwar
Keyword(s):  
Stem Cell ◽  
G Protein ◽  
Cell Biology ◽  
Myeloproliferative Neoplasms ◽  
Stem Cell Maintenance ◽  
Health And Disease ◽  
Stem Cell Populations ◽  
Cell Phenotypes ◽  
Cell Maintenance

β-Arrestins (ARRBs) are ubiquitously expressed scaffold proteins that mediate inactivation of G-protein-coupled receptor signaling, and in certain circumstances, G-protein independent pathways. Intriguingly, the two known ARRBs, β-arrestin1 (ARRB1) and β-Arrestin2 (ARRB2), seem to have opposing functions in regulating signaling cascades in several models in health and disease. Recent evidence suggests that ARRBs are implicated in regulating stem cell maintenance; however, their role, although crucial, is complex, and there is no universal model for ARRB-mediated regulation of stem cell characteristics. For the first time, this review compiles information on the function of ARRBs in stem cell biology and will discuss the role of ARRBs in regulating cell signaling pathways implicated in stem cell maintenance in normal and malignant stem cell populations. Although promising targets for cancer therapy, the ubiquitous nature of ARRBs and the plethora of functions in normal cell biology brings challenges for treatment selectivity. However, recent studies show promising evidence for specifically targeting ARRBs in myeloproliferative neoplasms.

Testosterone Potentiation of Ionophore and ADP Induced Platelet Aggregation : Relationship to Arachidonic Acid Metabolism

1981 ◽  
Vol 46 (02) ◽  
pp. 538-542 ◽  
Author(s):  
R Pilo ◽  
D Aharony ◽  
A Raz
Keyword(s):  
Arachidonic Acid ◽  
Platelet Aggregation ◽  
Unsaturated Fatty Acids ◽  
Human Platelet ◽  
Platelet Rich Plasma ◽  
Arachidonic Acid Metabolism ◽  
Ionophore A23187 ◽  
Low Concentrations ◽  
Induced Aggregation

SummaryThe role of arachidonic acid oxygenated products in human platelet aggregation induced by the ionophore A23187 was investigated. The ionophore produced an increased release of both saturated and unsaturated fatty acids and a concomitant increased formation of TxA2 and other arachidonate products. TxA2 (and possibly other cyclo oxygenase products) appears to have a significant role in ionophore-induced aggregation only when low concentrations (<1 μM) of the ionophore are employed.Testosterone added to rat or human platelet-rich plasma (PRP) was shown previously to potentiate platelet aggregation induced by ADP, adrenaline, collagen and arachidonic acid (1, 2). We show that testosterone also potentiates ionophore induced aggregation in washed platelets and in PRP. This potentiation was dose and time dependent and resulted from increased lipolysis and concomitant generation of TxA2 and other prostaglandin products. The testosterone potentiating effect was abolished by preincubation of the platelets with indomethacin.

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