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Plant Physiology and Biochemistry : PPB Feb 2024Abiotic stress is one of the main threats affecting crop growth and production. Nitric oxide (NO), an important signaling molecule involved in wide range of plant growth... (Review)
Review
Abiotic stress is one of the main threats affecting crop growth and production. Nitric oxide (NO), an important signaling molecule involved in wide range of plant growth and development as well as in response to abiotic stress. NO can exert its biological functions through protein S-nitrosylation, a redox-based posttranslational modification by covalently adding NO moiety to a reactive cysteine thiol of a target protein to form an S-nitrosothiol (SNO). Protein S-nitrosylation is an evolutionarily conserved mechanism regulating multiple aspects of cellular signaling in plant. Recently, emerging evidence have elucidated protein S-nitrosylation as a modulator of plant in responses to abiotic stress, including salt stress, extreme temperature stress, light stress, heavy metal and drought stress. In addition, significant mechanism has been made in functional characterization of protein S-nitrosylated candidates, such as changing protein conformation, and the subcellular localization of proteins, regulating protein activity and influencing protein interactions. In this study, we updated the data related to protein S-nitrosylation in plants in response to adversity and gained a deeper understanding of the functional changes of target proteins after protein S-nitrosylation.
Topics: Plants; Nitric Oxide; Plant Development; Signal Transduction; Stress, Physiological; Protein Processing, Post-Translational
PubMed: 38184883
DOI: 10.1016/j.plaphy.2023.108329 -
Frontiers in Neuroscience 2020Manganese (Mn), an essential micronutrient, acts as a cofactor for multiple enzymes. Epidemiological investigations have shown that an excessive level of Mn is an... (Review)
Review
Manganese (Mn), an essential micronutrient, acts as a cofactor for multiple enzymes. Epidemiological investigations have shown that an excessive level of Mn is an important environmental factor involved in neurotoxicity. Frequent pollution of air and water by Mn is a serious threat to the health of the population. Overexposure to Mn is particularly detrimental to the central nervous system, leading to symptoms similar to several neurological disorders. Many different mechanisms have been implicated in Mn-induced neurotoxicity, including oxidative/nitrosative stress, toxic protein aggregation, endoplasmic reticulum (ER) stress, mitochondrial dysfunction, dysregulation of autophagy, and the apoptotic cascade, which together promote the progressive neurodegeneration of nerve cells. As a compensatory regulatory mechanism, autophagy plays dual roles in various biological activities under pathological stress conditions. Dysregulation of autophagy is involved in the development of neurodegenerative disorders, with recent emerging evidence indicating a strong, complex relationship between autophagy and Mn-induced neurotoxicity. This review discusses the connection between autophagy and Mn-induced neurotoxicity, especially alpha-synuclein oligomerization, ER stress, and aberrated protein S-nitrosylation, which will provide new insights to profoundly explore the precise mechanisms of Mn-induced neurotoxicity.
PubMed: 33041767
DOI: 10.3389/fnins.2020.574750 -
Ageing Research Reviews Apr 2022Hydrogen sulfide (HS) and hydrogen polysulfides (HS) are essential regulatory signaling molecules generated by the entire body, including the central nervous system.... (Review)
Review
Hydrogen sulfide (HS) and hydrogen polysulfides (HS) are essential regulatory signaling molecules generated by the entire body, including the central nervous system. Researchers have focused on the classical HS signaling from the past several decades, whereas the last decade has shown the emergence of HS-induced protein S-sulfhydration signaling as a potential therapeutic approach. Cysteine S-persulfidation is a critical paradigm of post-translational modification in the process of HS signaling. Additionally, studies have shown the cross-relationship between S-sulfhydration and other cysteine-induced post-translational modifications, namely nitrosylation and carbonylation. In the central nervous system, S-sulfhydration is involved in the cytoprotection through various signaling pathways, viz. inflammatory response, oxidative stress, endoplasmic reticulum stress, atherosclerosis, thrombosis, and angiogenesis. Further, studies have demonstrated HS-induced S-sulfhydration in regulating different biological processes, such as mitochondrial integrity, calcium homeostasis, blood-brain permeability, cerebral blood flow, and long-term potentiation. Thus, protein S-sulfhydration becomes a crucial regulatory molecule in cerebrovascular and neurodegenerative diseases. Herein, we first described the generation of intracellular HS followed by the application of HS in the regulation of cerebral blood flow and blood-brain permeability. Further, we described the involvement of S-sulfhydration in different biological and cellular functions, such as inflammatory response, mitochondrial integrity, calcium imbalance, and oxidative stress. Moreover, we highlighted the importance of S-sulfhydration in cerebrovascular and neurodegenerative diseases.
Topics: Brain; Calcium; Cysteine; Humans; Hydrogen Sulfide; Prospective Studies; Protein S
PubMed: 35124235
DOI: 10.1016/j.arr.2022.101579 -
Clinical Laboratory Aug 2022Protein S is a central regulator of coagulation as it critically participates in down-regulation of both extrinsic and intrinsic pathways of the coagulation cascade. In... (Review)
Review
BACKGROUND
Protein S is a central regulator of coagulation as it critically participates in down-regulation of both extrinsic and intrinsic pathways of the coagulation cascade. In this review, we aim to provide an update on protein S and its anticoagulant functions as a central hemostatic regulator.
METHODS
Electronic databases including, Google, Google Scholar, PMC, PubMed, Science Direct, and Scopus were rigorously searched using the terms protein S, hemostasis, natural anticoagulants, regulators of coagulation, and coagulation inhibitors for the completion of this descriptive review.
RESULTS
Literature review shows that protein S is a potent cofactor for activated protein C (APC) in the regulation of the intrinsic pathway and a cofactor for tissue factor pathway inhibitor (TFPI) in the regulation of the extrinsic pathway. The strong association between protein S deficiency either hereditary or acquired and increased risk for venous thrombosis indicates the important and central role of protein S in controlling the initiation and propagation phase of coagulation cascade and that protein S is an important determinant for optimal activity of both APC and TFPI in coagulation regulation.
CONCLUSIONS
Available evidence suggests that the role of protein S in the down-regulation of blood coagulation is mainly mediated through its high affinity binding to negatively charged phospholipid surfaces. This high affinity binding to negatively charged phospholipids helps bring the anticoagulant proteins to the membranes, resulting in efficient and targeted regulation of coagulation. In the shade of current COVID-19 pandemic, protein S deficiency has been found to be a leading cause of thrombotic complications associated with COVID-19.
Topics: Anticoagulants; Blood Coagulation; COVID-19; Humans; Protein S; Protein S Deficiency
PubMed: 35975485
DOI: 10.7754/Clin.Lab.2021.211010 -
Journal of the American Heart... Feb 2022Background Five classic thrombophilias have been recognized: factor V Leiden (rs6025), the prothrombin G20210A variant (rs1799963), and protein C, protein S, and...
Background Five classic thrombophilias have been recognized: factor V Leiden (rs6025), the prothrombin G20210A variant (rs1799963), and protein C, protein S, and antithrombin deficiencies. This study aimed to determine the thrombotic risk of classic thrombophilias in a cohort of middle-aged and older adults. Methods and Results Factor V Leiden, prothrombin G20210A and protein-coding variants in the (protein C), (protein S), and (antithrombin) anticoagulant genes were determined in 29 387 subjects (born 1923-1950, 60% women) who participated in the Malmö Diet and Cancer study (1991-1996). The Human Gene Mutation Database was used to define 68 disease-causing mutations. Patients were followed up from baseline until the first event of venous thromboembolism (VTE), death, or Dec 31, 2018. Carriership (n=908, 3.1%) for disease-causing mutations in the , , and genes was associated with incident VTE: Hazard ratio (HR) was 1.6 (95% CI, 1.3-1.9). Variants not in Human Gene Mutation Database were not linked to VTE (HR, 1.1; 95% CI, 0.8-1.5). Heterozygosity for rs6025 and rs1799963 was associated with incident VTE: HR, 1.8 (95% CI, 1.6-2.0) and HR, 1.6 (95% CI, 1.3-2.0), respectively. The HR for carrying 1 classical thrombophilia variant was 1.7 (95% CI, 1.6-1.9). HR was 3.9 (95% CI, 3.1-5.0) for carriers of ≥2 thrombophilia variants. Conclusions The 5 classic thrombophilias are associated with a dose-graded risk of VTE in middle-aged and older adults. Disease-causing variants in the , , and genes were more common than the rs1799963 variant but the conferred genetic risk was comparable with the rs6025 and rs1799963 variants.
Topics: Aged; Anticoagulants; Antithrombins; Cohort Studies; Factor V; Female; Humans; Male; Middle Aged; Mutation; Protein C; Protein S; Prothrombin; Risk Factors; Thrombophilia; Thrombosis; Venous Thromboembolism
PubMed: 35112923
DOI: 10.1161/JAHA.121.023018 -
Antioxidants (Basel, Switzerland) Dec 2021Ischemia-reperfusion injury (IRI) is a process in which damage is induced in hypoxic tissue when oxygen supply is resumed after ischemia. During IRI, restoration of... (Review)
Review
Ischemia-reperfusion injury (IRI) is a process in which damage is induced in hypoxic tissue when oxygen supply is resumed after ischemia. During IRI, restoration of reduced nitric oxide (NO) levels may alleviate reperfusion injury in ischemic organs. The protective mechanism of NO is due to anti-inflammatory effects, antioxidant effects, and the regulation of cell signaling pathways. On the other hand, it is generally known that S-nitrosylation (SNO) mediates the detrimental or protective effect of NO depending on the action of the nitrosylated target protein, and this is also applied in the IRI process. In this review, the effect of each change of NO and SNO during the IRI process was investigated.
PubMed: 35052559
DOI: 10.3390/antiox11010057 -
Frontiers in Cardiovascular Medicine 2021Plasma levels of the anticoagulant cofactor protein S and PROS1 mutation are reported to impart increased risk of thromboembolism in European and south east Asian...
Plasma levels of the anticoagulant cofactor protein S and PROS1 mutation are reported to impart increased risk of thromboembolism in European and south east Asian populations, but the relationship is not yet documented in Han Chinese in population-based study. Therefore, we undertook a case-control study of this relationship among patients with venous thromboembolism, and probed the genetic factors contributing to low protein S deficiency. Among the 603 consecutively recruited venous thromboembolism patients, 51 (8.5%) proved to be deficient in free protein S antigen (lower than 38.6 U/dl), among whom 30 cases were identified to have a causative mutation by direct sequencing. In contrast, six cases (1.0%) of the 584 healthy controls had low free antigen levels, among whom direct sequencing confirmed disease-causing gene mutations in four controls (0.7%). After adjusting for age and gender, the odds ratio of developing venous thromboembolism in individuals with protein S deficiency based on free protein S tests was 8.1 (95% CI = 3.6-19.9, < 0.001). Gene sequencing yielded 24 different heterozygous mutations in the 34 participants, of which 13 were newly described. 17 (50%) of the 34 mutations in our study cohort occurred in exons 12 and 13, indicating the LGR2 domain to be a hotspot mutation region for the protein. These findings are conducive to the clinical application of protein S assays for the molecular diagnosis of thrombophilia.
PubMed: 35815065
DOI: 10.3389/fcvm.2021.796755 -
Seminars in Thrombosis and Hemostasis May 2024Although inherited thrombophilias are lifelong risk factors for a first thrombotic episode, progression to thrombosis is multifactorial and not all individuals with...
Although inherited thrombophilias are lifelong risk factors for a first thrombotic episode, progression to thrombosis is multifactorial and not all individuals with inherited thrombophilia develop thrombosis in their lifetimes. Consequently, indiscriminate screening in patients with idiopathic thrombosis is not recommended, since presence of a thrombophilia does not necessarily predict recurrence or influence management, and testing should be selective. It follows that a decision to undertake laboratory detection of thrombophilia should be aligned with a concerted effort to identify any significant abnormalities, because it will inform patient management. Deficiencies of antithrombin and protein C are rare and usually determined using phenotypic assays assessing biological activities, whereas protein S deficiency (also rare) is commonly detected with antigenic assays for the free form of protein S since available activity assays are considered to lack specificity. In each case, no single phenotypic assay is capable of detecting every deficiency, because the various mutations express different molecular characteristics, rendering thrombophilia screening repertoires employing one assay per potential deficiency, of limited effectiveness. Activated protein C resistance (APCR) is more common than discrete deficiencies of antithrombin, protein C, and protein S and also often detected initially with phenotypic assays; however, some centres perform only genetic analysis for factor V Leiden, as this is responsible for most cases of hereditary APCR, accepting that acquired APCR and rare mutations conferring APCR will go undetected if only factor V Leiden is evaluated. All phenotypic assays have interferences and limitations, which must be factored into decisions about if, and when, to test, and be given consideration in the laboratory during assay performance and interpretation. This review looks in detail at performance and limitations of routine phenotypic thrombophilia assays.
PubMed: 38733983
DOI: 10.1055/s-0044-1786807 -
The FEBS Journal Feb 2022The lipid post-translational modification S-palmitoylation is a vast developing field, with the modification itself and the enzymes that catalyse the reversible reaction... (Review)
Review
The lipid post-translational modification S-palmitoylation is a vast developing field, with the modification itself and the enzymes that catalyse the reversible reaction implicated in a number of diseases. In this review, we discuss the past and recent advances in the experimental tools used in this field, including pharmacological tools, animal models and techniques to understand how palmitoylation controls protein localisation and function. Additionally, we discuss the obstacles to overcome in order to advance the field, particularly to the point at which modulating palmitoylation may be achieved as a therapeutic strategy.
Topics: Animals; Humans; Lipid Metabolism; Lipids; Lipoylation; Protein S
PubMed: 33624421
DOI: 10.1111/febs.15781 -
Journal of Proteome Research Jan 2021Protein -acylation (commonly known as palmitoylation) is a widespread reversible lipid modification, which plays critical roles in regulating protein localization,... (Review)
Review
Protein -acylation (commonly known as palmitoylation) is a widespread reversible lipid modification, which plays critical roles in regulating protein localization, activity, stability, and complex formation. The deregulation of protein -acylation contributes to many diseases such as cancer and neurodegenerative disorders. The past decade has witnessed substantial progress in proteomic analysis of protein -acylation, which significantly advanced our understanding of -acylation biology. In this review, we summarized the techniques for the enrichment of -acylated proteins or peptides, critically reviewed proteomic studies of protein -acylation at eight different levels, and proposed major challenges for the -acylproteomics field. In summary, proteome-scale analysis of protein -acylation comes of age and will play increasingly important roles in discovering new disease mechanisms, biomarkers, and therapeutic targets.
Topics: Acylation; Lipoylation; Protein S; Proteome; Proteomics
PubMed: 33253586
DOI: 10.1021/acs.jproteome.0c00409