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 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 Serine protease inhibitors and human wellbeing interplay: new insights for old friends

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e7224 ◽  
Author(s):  
Héla Mkaouar ◽  
Nizar Akermi ◽  
Aicha Kriaa ◽  
Anne-Laure Abraham ◽  
Amin Jablaoui ◽  
...  
Keyword(s):  
Serine Protease ◽  
Protease Inhibitors ◽  
Structural Data ◽  
Ecological Niches ◽  
Serine Protease Inhibitors ◽  
New Therapeutic Approaches ◽  
Physiological Processes ◽  
Health And Disease ◽  
And Function

Serine Protease Inhibitors (Serpins) control tightly regulated physiological processes and their dysfunction is associated to various diseases. Thus, increasing interest is given to these proteins as new therapeutic targets. Several studies provided functional and structural data about human serpins. By comparison, only little knowledge regarding bacterial serpins exists. Through the emergence of metagenomic studies, many bacterial serpins were identified from numerous ecological niches including the human gut microbiota. The origin, distribution and function of these proteins remain to be established. In this report, we shed light on the key role of human and bacterial serpins in health and disease. Moreover, we analyze their function, phylogeny and ecological distribution. This review highlights the potential use of bacterial serpins to set out new therapeutic approaches.

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.

scholarly journals Scrapie Protein Degradation by Cysteine Proteases in CD11c+ Dendritic Cells and GT1-1 Neuronal Cells

2004 ◽  
Vol 78 (9) ◽  
pp. 4776-4782 ◽  
Author(s):  
Katarina M. Luhr ◽  
Elin K. Nordström ◽  
Peter Löw ◽  
Hans-Gustaf Ljunggren ◽  
Albert Taraboulos ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Protease Inhibitors ◽  
Cysteine Protease ◽  
Prion Proteins ◽  
Neuronal Cell ◽  
Cysteine Proteases ◽  
Proteinase K ◽  
Cysteine Protease Inhibitors

ABSTRACT Dendritic cells (DC) of the CD11c+ myeloid phenotype have been implicated in the spread of scrapie in the host. Previously, we have shown that CD11c+ DC can cause a rapid degradation of proteinase K-resistant prion proteins (PrPSc) in vitro, indicating a possible role of these cells in the clearance of PrPSc. To determine the mechanisms of PrPSc degradation, CD11c+ DC that had been exposed to PrPSc derived from a neuronal cell line (GT1-1) infected with scrapie (ScGT1-1) were treated with a battery of protease inhibitors. Following treatment with the cysteine protease inhibitors (2S,3S)-trans-epoxysuccinyl-l-leucylamido-3-methylbutane (E-64c), its ethyl ester (E-64d), and leupeptin, the degradation of PrPSc was inhibited, while inhibitors of serine and aspartic and metalloproteases (aprotinin, pepstatin, and phosphoramidon) had no effect. An endogenous degradation of PrPSc in ScGT1-1 cells was revealed by inhibiting the expression of cellular PrP (PrPC) by RNA interference, and this degradation could also be inhibited by the cysteine protease inhibitors. Our data show that PrPSc is proteolytically cleaved preferentially by cysteine proteases in both CD11c+ DC and ScGT1-1 cells and that the degradation of PrPSc by proteases is different from that of PrPC. Interference by protease inhibitors with DC-induced processing of PrPSc has the potential to modify prion spread, clearance, and immunization in a host.

The role of compulsory periodical medical examination in employee’s dental health maintenance

2020 ◽  
pp. 678-678
Author(s):  
E. Y. Leontyeva ◽  
T. Y. Bykovskaya
Keyword(s):  
Oral Cavity ◽  
Dental Health ◽  
Medical Examination ◽  
Health Maintenance

The analysis of the appealability for the rehabilitation of the oral cavity of staff subject to mandatory periodic examinations at the dentist. The growth of indicators characterizing the dental activity of employees was noted. Subject to the principle of continuity, annual mandatory periodic examinations can be one of the factors in maintaining the dental health of employees.

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