Physiological researchPub Date : 2024-08-30Epub Date: 2024-06-05DOI: 10.33549/physiolres.935406
K Papoušková, K Černá, V Radova, O Zimmermannová
{"title":"The Role of Cornichons in the Biogenesis and Functioning of Monovalent-Cation Transport Systems.","authors":"K Papoušková, K Černá, V Radova, O Zimmermannová","doi":"10.33549/physiolres.935406","DOIUrl":"10.33549/physiolres.935406","url":null,"abstract":"<p><p>Monovalent-cation homeostasis, crucial for all living cells, is ensured by the activity of various types of ion transport systems located either in the plasma membrane or in the membranes of organelles. A key prerequisite for the functioning of ion-transporting proteins is their proper trafficking to the target membrane. The cornichon family of COPII cargo receptors is highly conserved in eukaryotic cells. By simultaneously binding their cargoes and a COPII-coat subunit, cornichons promote the incorporation of cargo proteins into the COPII vesicles and, consequently, the efficient trafficking of cargoes via the secretory pathway. In this review, we summarize current knowledge about cornichon proteins (CNIH/Erv14), with an emphasis on yeast and mammalian cornichons and their role in monovalent-cation homeostasis. Saccharomyces cerevisiae cornichon Erv14 serves as a cargo receptor of a large portion of plasma-membrane proteins, including several monovalent-cation transporters. By promoting the proper targeting of at least three housekeeping ion transport systems, Na+, K+/H+ antiporter Nha1, K+ importer Trk1 and K+ channel Tok1, Erv14 appears to play a complex role in the maintenance of alkali-metal-cation homeostasis. Despite their connection to serious human diseases, the repertoire of identified cargoes of mammalian cornichons is much more limited. The majority of current information is about the structure and functioning of CNIH2 and CNIH3 as auxiliary subunits of AMPAR multi-protein complexes. Based on their unique properties and easy genetic manipulation, we propose yeast cells to be a useful tool for uncovering a broader spectrum of human cornichons´ cargoes.</p>","PeriodicalId":20235,"journal":{"name":"Physiological research","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11412353/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141248042","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Physiological researchPub Date : 2024-08-30Epub Date: 2024-07-02DOI: 10.33549/physiolres.935401
M Neřoldová, A Stuchlík
{"title":"Chemogenetic Tools and their Use in Studies of Neuropsychiatric Disorders.","authors":"M Neřoldová, A Stuchlík","doi":"10.33549/physiolres.935401","DOIUrl":"10.33549/physiolres.935401","url":null,"abstract":"<p><p>Chemogenetics is a newly developed set of tools that allow for selective manipulation of cell activity. They consist of a receptor mutated irresponsive to endogenous ligands and a synthetic ligand that does not interact with the wild-type receptors. Many different types of these receptors and their respective ligands for inhibiting or excitating neuronal subpopulations were designed in the past few decades. It has been mainly the G-protein coupled receptors (GPCRs) selectively responding to clozapine-N-oxide (CNO), namely Designer Receptors Exclusively Activated by Designer Drugs (DREADDs), that have been employed in research. Chemogenetics offers great possibilities since the activity of the receptors is reversible, inducible on demand by the ligand, and non-invasive. Also, specific groups or types of neurons can be selectively manipulated thanks to the delivery by viral vectors. The effect of the chemogenetic receptors on neurons lasts longer, and even chronic activation can be achieved. That can be useful for behavioral testing. The great advantage of chemogenetic tools is especially apparent in research on brain diseases since they can manipulate whole neuronal circuits and connections between different brain areas. Many psychiatric or other brain diseases revolve around the dysfunction of specific brain networks. Therefore, chemogenetics presents a powerful tool for investigating the underlying mechanisms causing the disease and revealing the link between the circuit dysfunction and the behavioral or cognitive symptoms observed in patients. It could also contribute to the development of more effective treatments.</p>","PeriodicalId":20235,"journal":{"name":"Physiological research","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11412350/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141493048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Physiological researchPub Date : 2024-08-30Epub Date: 2024-05-15DOI: 10.33549/physiolres.935293
M Dzubanova, A Benova, M Ferencakova, R Coupeau, M Tencerova
{"title":"Nutrition and Bone Marrow Adiposity in Relation to Bone Health.","authors":"M Dzubanova, A Benova, M Ferencakova, R Coupeau, M Tencerova","doi":"10.33549/physiolres.935293","DOIUrl":"10.33549/physiolres.935293","url":null,"abstract":"<p><p>Bone remodeling is energetically demanding process. Energy coming from nutrients present in the diet contributes to function of different cell type including osteoblasts, osteocytes and osteoclasts in bone marrow participating in bone homeostasis. With aging, obesity and osteoporosis the function of key building blocks, bone marrow stromal cells (BMSCs), changes towards higher accumulation of bone marrow adipose tissue (BMAT) and decreased bone mass, which is affected by diet and sex dimorphism. Men and women have unique nutritional needs based on physiological and hormonal changes across the life span. However, the exact molecular mechanisms behind these pathophysiological conditions in bone are not well-known. In this review, we focus on bone and BMAT physiology in men and women and how this approach has been taken by animal studies. Furthermore, we discuss the different diet interventions and impact on bone and BMAT in respect to sex differences. We also discuss the future perspective on precision nutrition with a consideration of sex-based differences which could bring better understanding of the diet intervention in bone health and weight management.</p>","PeriodicalId":20235,"journal":{"name":"Physiological research","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11412336/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140944551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Physiological researchPub Date : 2024-08-30Epub Date: 2024-04-22DOI: 10.33549/physiolres.935292
J Janáček
{"title":"Mathematical Models of Diffusion in Physiology.","authors":"J Janáček","doi":"10.33549/physiolres.935292","DOIUrl":"10.33549/physiolres.935292","url":null,"abstract":"<p><p>Diffusion is a mass transport phenomenon caused by chaotic thermal movements of molecules. Studying the transport in specific domain is simplified by using evolutionary differential equations for local concentration of the molecules instead of complete information on molecular paths [1]. Compounds in a fluid mixture tend to smooth out its spatial concentration inhomogeneities by diffusion. Rate of the transport is proportional to the concentration gradient and coefficient of diffusion of the compound in ordinary diffusion. The evolving concentration profile c(x,t) is then solution of evolutionary partial differential equation deltac/deltat=DDeltac where D is diffusion coefficient and Delta is Laplacian operator. Domain of the equation may be a region in space, plane or line, a manifold, such as surface embedded in space, or a graph. The Laplacian operates on smooth functions defined on given domain. We can use models of diffusion for such diverse tasks as: a) design of method for precise measurement of receptors mobility in plasmatic membrane by confocal microscopy [2], b) evaluation of complex geometry of trabeculae in developing heart [3] to show that the conduction pathway within the embryonic ventricle is determined by geometry of the trabeculae.</p>","PeriodicalId":20235,"journal":{"name":"Physiological research","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11412344/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140874780","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Physiological researchPub Date : 2024-08-30Epub Date: 2024-04-22DOI: 10.33549/physiolres.935306
V Obsilova, T Obsil
{"title":"Look for the Scaffold: Multifaceted Regulation of Enzyme Activity by 14-3-3 Proteins.","authors":"V Obsilova, T Obsil","doi":"10.33549/physiolres.935306","DOIUrl":"10.33549/physiolres.935306","url":null,"abstract":"<p><p>Enzyme activity is regulated by several mechanisms, including phosphorylation. Phosphorylation is a key signal transduction process in all eukaryotic cells and is thus crucial for virtually all cellular processes. In addition to its direct effect on protein structure, phosphorylation also affects protein-protein interactions, such as binding to scaffolding 14-3-3 proteins, which selectively recognize phosphorylated motifs. These interactions then modulate the catalytic activity, cellular localisation and interactions of phosphorylated enzymes through different mechanisms. The aim of this mini-review is to highlight several examples of 14-3-3 protein-dependent mechanisms of enzyme regulation previously studied in our laboratory over the past decade. More specifically, we address here the regulation of the human enzymes ubiquitin ligase Nedd4-2, procaspase-2, calcium-calmodulin dependent kinases CaMKK1/2, and death-associated protein kinase 2 (DAPK2) and yeast neutral trehalase Nth1.</p>","PeriodicalId":20235,"journal":{"name":"Physiological research","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11412345/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140865702","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Physiological researchPub Date : 2024-08-30Epub Date: 2024-04-22DOI: 10.33549/physiolres.935259
B Holendová, Š Benáková, M Křivonosková, L Plecitá-Hlavatá
{"title":"Redox Status as a Key Driver of Healthy Pancreatic Beta-Cells.","authors":"B Holendová, Š Benáková, M Křivonosková, L Plecitá-Hlavatá","doi":"10.33549/physiolres.935259","DOIUrl":"10.33549/physiolres.935259","url":null,"abstract":"<p><p>Redox status plays a multifaceted role in the intricate physiology and pathology of pancreatic beta-cells, the pivotal regulators of glucose homeostasis through insulin secretion. They are highly responsive to changes in metabolic cues where reactive oxygen species are part of it, all arising from nutritional intake. These molecules not only serve as crucial signaling intermediates for insulin secretion but also participate in the nuanced heterogeneity observed within the beta-cell population. A central aspect of beta-cell redox biology revolves around the localized production of hydrogen peroxide and the activity of NADPH oxidases which are tightly regulated and serve diverse physiological functions. Pancreatic beta-cells possess a remarkable array of antioxidant defense mechanisms although considered relatively modest compared to other cell types, are efficient in preserving redox balance within the cellular milieu. This intrinsic antioxidant machinery operates in concert with redox-sensitive signaling pathways, forming an elaborate redox relay system essential for beta-cell function and adaptation to changing metabolic demands. Perturbations in redox homeostasis can lead to oxidative stress exacerbating insulin secretion defect being a hallmark of type 2 diabetes. Understanding the interplay between redox signaling, oxidative stress, and beta-cell dysfunction is paramount for developing effective therapeutic strategies aimed at preserving beta-cell health and function in individuals with type 2 diabetes. Thus, unraveling the intricate complexities of beta-cell redox biology presents exciting avenues for advancing our understanding and treatment of metabolic disorders.</p>","PeriodicalId":20235,"journal":{"name":"Physiological research","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11412338/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140857279","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Physiological researchPub Date : 2024-08-30Epub Date: 2024-07-02DOI: 10.33549/physiolres.935371
D Spicarova, J Palecek
{"title":"Anandamide-Mediated Modulation of Nociceptive Transmission at the Spinal Cord Level.","authors":"D Spicarova, J Palecek","doi":"10.33549/physiolres.935371","DOIUrl":"10.33549/physiolres.935371","url":null,"abstract":"<p><p>Three decades ago, the first endocannabinoid, anandamide (AEA), was identified, and its analgesic effect was recognized in humans and preclinical models. However, clinical trial failures pointed out the complexity of the AEA-induced analgesia. The first synapses in the superficial laminae of the spinal cord dorsal horn represent an important modulatory site in nociceptive transmission and subsequent pain perception. The glutamatergic synaptic transmission at these synapses is strongly modulated by two primary AEA-activated receptors, cannabinoid receptor 1 (CB1) and transient receptor potential vanilloid 1 (TRPV1), both highly expressed on the presynaptic side formed by the endings of primary nociceptive neurons. Activation of these receptors can have predominantly inhibitory (CB1) and excitatory (TRPV1) effects that are further modulated under pathological conditions. In addition, dual AEA-mediated signaling and action may occur in primary sensory neurons and dorsal horn synapses. AEA application causes balanced inhibition and excitation of primary afferent synaptic input on superficial dorsal horn neurons in normal conditions, whereas peripheral inflammation promotes AEA-mediated inhibition. This review focuses mainly on the modulation of synaptic transmission at the spinal cord level and signaling in primary nociceptive neurons by AEA via CB1 and TRPV1 receptors. Furthermore, the spinal analgesic effect in preclinical studies and clinical aspects of AEA-mediated analgesia are considered.</p>","PeriodicalId":20235,"journal":{"name":"Physiological research","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11412359/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141493047","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Physiological researchPub Date : 2024-08-30Epub Date: 2024-05-15DOI: 10.33549/physiolres.935361
K Bardova, P Janovska, A Vavrova, J Kopecky, P Zouhar
{"title":"Adaptive Induction of Nonshivering Thermogenesis in Muscle Rather Than Brown Fat Could Counteract Obesity.","authors":"K Bardova, P Janovska, A Vavrova, J Kopecky, P Zouhar","doi":"10.33549/physiolres.935361","DOIUrl":"10.33549/physiolres.935361","url":null,"abstract":"<p><p>Warm-blooded animals such as birds and mammals are able to protect stable body temperature due to various thermogenic mechanisms. These processes can be facultative (occurring only under specific conditions, such as acute cold) and adaptive (adjusting their capacity according to long-term needs). They can represent a substantial part of overall energy expenditure and, therefore, affect energy balance. Classical mechanisms of facultative thermogenesis include shivering of skeletal muscles and (in mammals) non-shivering thermogenesis (NST) in brown adipose tissue (BAT), which depends on uncoupling protein 1 (UCP1). Existence of several alternative thermogenic mechanisms has been suggested. However, their relative contribution to overall heat production and the extent to which they are adaptive and facultative still needs to be better defined. Here we focus on comparison of NST in BAT with thermogenesis in skeletal muscles, including shivering and NST. We present indications that muscle NST may be adaptive but not facultative, unlike UCP1-dependent NST. Due to its slow regulation and low energy efficiency, reflecting in part the anatomical location, induction of muscle NST may counteract development of obesity more effectively than UCP1-dependent thermogenesis in BAT.</p>","PeriodicalId":20235,"journal":{"name":"Physiological research","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11412341/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140944482","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Epilepsy Research in the Institute of Physiology of the Czech Academy of Sciences in Prague.","authors":"P Mareš","doi":"10.33549/physiolres.935391","DOIUrl":"10.33549/physiolres.935391","url":null,"abstract":"<p><p>Starting from simple clinical statistics, the spectrum of methods used in epilepsy research in the Institute of Physiology of the Czechoslovak (now Czech) Academy of Sciences progressively increased. Professor Servít used electrophysiological methods for study of brain activity in lower vertebrates, neuropathology was focused on electronmicroscopic study of cortical epileptic focus and ion-sensitive microelectrodes were used for studies of cortical direct current potentials. Developmental studies used electrophysiological methods (activity and projection of cortical epileptic foci, EEG under the influence of convulsant drugs, hippocampal, thalamic and cortical electrical stimulation for induction of epileptic afterdischarges and postictal period). Extensive pharmacological studies used seizures elicited by convulsant drugs (at first pentylenetetrazol but also other GABA antagonists as well as agonists of glutamate receptors). Motor performance and behavior were also studied during brain maturation. The last but not least molecular biology was included into the spectrum of methods. Many original data were published making a background of position of our laboratory in the first line of laboratories interested in brain development.</p>","PeriodicalId":20235,"journal":{"name":"Physiological research","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11412343/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140944583","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Physiological researchPub Date : 2024-08-30Epub Date: 2024-07-02DOI: 10.33549/physiolres.935414
F Vyskočil
{"title":"From Frog Muscle to Brain Neurons: Joys and Sorrows in Neuroscience.","authors":"F Vyskočil","doi":"10.33549/physiolres.935414","DOIUrl":"10.33549/physiolres.935414","url":null,"abstract":"<p><p>One element, potassium, can be identified as the connecting link in the research of Czech neurophysiologist Prof. František Vyskočil. It accompanied him from the first student experiments on the frog muscle (Solandt effect) via sodium-potassium pump and quantum and non-quantum release of neurotransmitters (e.g. acetylcholine) to the most appreciated work on the reversible leakage of K+ from brain neurons during the Leao´s spreading cortical depression, often preceding migraine. He used a wide range of methods at the systemic, cellular and genetic levels. The electrophysiology and biochemistry of nerve-muscle contacts and synapses in the muscles and brain led to a range of interesting findings and discoveries on normal, denervated and hibernating laboratory mammals and in tissue cultures. Among others, he co-discovered the facilitating effects of catecholamines (adrenaline in particular) by end-plate synchronization of individual evoked quanta. This helps to understand the general effectiveness of nerve-muscle performance during actual stress. After the transition of the Czech Republic to capitalism, together with Dr. Josef Zicha from our Institute, he was an avid promoter of scientometry as an objective system of estimating a scientist´s success in basic research (journal Vesmír, 69: 644-645, 1990 in Czech).</p>","PeriodicalId":20235,"journal":{"name":"Physiological research","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11412337/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141493049","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}