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":" ","pages":"S401-S412"},"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":" ","pages":"S139-S152"},"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":" ","pages":"S435-S448"},"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":" ","pages":"S279-S294"},"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":" ","pages":"S67-S82"},"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":" ","pages":"S83-S103"},"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}
J Kristek, E Sticova, J Chlupac, H Cermakova, J Maluskova, L Janousek, M Olausson, J Fronek
{"title":"Corrigendum for: Early Uterine Transplant Graft Loss Due to Thrombosis: Single-Center Experience With Causes, Prevention, Diagnosis, and Treatment.","authors":"J Kristek, E Sticova, J Chlupac, H Cermakova, J Maluskova, L Janousek, M Olausson, J Fronek","doi":"10.33549/physiolres.930000.73.485","DOIUrl":"10.33549/physiolres.930000.73.485","url":null,"abstract":"<p><p>On the basis of author's request the publisher of Physiological Research decided to change the license of the article to CC BY license.</p>","PeriodicalId":20235,"journal":{"name":"Physiological research","volume":"73 3","pages":"485"},"PeriodicalIF":1.9,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141724246","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Maternal-Fetal Microchimerism: Impacts on Offspring's Immune Development and Transgenerational Immune Memory Transfer.","authors":"N Malinská, V Grobárová, K Knížková, J Černý","doi":"10.33549/physiolres.935296","DOIUrl":"10.33549/physiolres.935296","url":null,"abstract":"<p><p>Maternal-fetal microchimerism is a fascinating phenomenon in which maternal cells migrate to the tissues of the offspring during both pregnancy and breastfeeding. These cells primarily consist of leukocytes and stem cells. Remarkably, these maternal cells possess functional potential in the offspring and play a significant role in shaping their immune system development. T lymphocytes, a cell population mainly found in various tissues of the offspring, have been identified as the major cell type derived from maternal microchimerism. These T lymphocytes not only exert effector functions but also influence the development of the offspring's T lymphocytes in the thymus and the maturation of B lymphocytes in the lymph nodes. Furthermore, the migration of maternal leukocytes also facilitates the transfer of immune memory across generations. Maternal microchimerism has also been observed to address immunodeficiencies in the offspring. This review article focuses on investigating the impact of maternal cells transported within maternal microchimerism on the immune system development of the offspring, as well as elucidating the effector functions of maternal cells that migrate through the placenta and breast milk to reach the offspring.</p>","PeriodicalId":20235,"journal":{"name":"Physiological research","volume":"73 3","pages":"315-332"},"PeriodicalIF":1.9,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11299782/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141724301","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":"Neurophysiological Assessment of H-Reflex Alterations in Compressive Radiculopathy.","authors":"P Šádek, E Hrušková, S Ostrý, J Otáhal","doi":"10.33549/physiolres.935325","DOIUrl":"10.33549/physiolres.935325","url":null,"abstract":"<p><p>This study aimed to investigate changes in the H-reflex recruitment curve in compressive radiculopathy, specifically assessing differences between symptomatic and asymptomatic limbs in patients with unilateral S1 radiculopathy through derived parameters. A total of 24 volunteers (15 male and 9 female, aged between 22 and 60 years) with confirmed nerve root compression in the L5/S1 segment participated. Nerve root compression was verified through clinical MRI examination and attributed to disc protrusion, spinal canal stenosis, or isthmic spondylolisthesis of L5/S1. Analysis revealed no difference in M-wave threshold intensity between symptomatic and non-symptomatic limbs. However, the H-reflex exhibited a trend toward increased threshold intensity in the symptomatic limb. Notably, a significant decrease in the slope of the H-reflex was observed on the symptomatic side, and the maximal H-reflex amplitude proved to be markedly different between the two limbs. The Hmax/Mmax ratio demonstrated a significant decrease in the symptomatic limb, indicating reduced effectiveness of signal translation. In conclusion, our findings emphasize the importance of H-reflex parameters in evaluating altered recruitment curves, offering valuable insights for neurological examinations. The observed differences in maximal values of M-wave, H-reflex, and their ratio in affected and unaffected limbs can enhance the diagnostic process for lumbosacral unilateral radiculopathy and contribute to a standardized approach in clinical assessments.</p>","PeriodicalId":20235,"journal":{"name":"Physiological research","volume":"73 3","pages":"427-433"},"PeriodicalIF":1.9,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11299786/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141724335","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":"Biological Mediators and Partial Regulatory Mechanisms on Neuropathic Pain Associated With Chemotherapeutic Agents.","authors":"Z Liu, S Liu, Y Zhao, Q Wang","doi":"10.33549/physiolres.935162","DOIUrl":"10.33549/physiolres.935162","url":null,"abstract":"<p><p>One of the most common issues caused by antineoplastic agents is chemotherapy-induced peripheral neuropathy (CIPN). In patients, CIPN is a sensory neuropathy accompanied by various motor and autonomic changes. With a high prevalence of cancer patients, CIPN is becoming a major problem for both cancer patients and for their health care providers. Nonetheless, there are lacking effective interventions preventing CIPN and treating the CIPN symptoms. A number of studies have demonstrated the cellular and molecular signaling pathways leading to CIPN using experimental models and the beneficial effects of some interventions on the CIPN symptoms related to those potential mechanisms. This review will summarize results obtained from recent human and animal studies, which include the abnormalities in mechanical and temperature sensory responses following chemotherapy such as representative bortezomib, oxaliplatin and paclitaxel. The underlying mechanisms of CIPN at cellular and molecular levels will be also discussed for additional in-depth studies needed to be better explored. Overall, this paper reviews the basic picture of CIPN and the signaling mechanisms of the most common antineoplastic agents in the peripheral and central nerve systems. A better understanding of the risk factors and fundamental mechanisms of CIPN is needed to develop effective preventive and therapeutic strategies.</p>","PeriodicalId":20235,"journal":{"name":"Physiological research","volume":"73 3","pages":"333-341"},"PeriodicalIF":1.9,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11299781/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141724244","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}