Search Results (81)

Background: Several mitochondrial abnormalities such as defective energy production, depletion of energy stores, Ca²⁺ accumulation, generation of reactive oxygen species, and impaired intracellular signaling are associated with cardiac dysfunction during the development of different heart diseases. Methods: A narrative review was compiled by a search for applicable literature in MEDLINE via PubMed. Results: Mitochondria generate ATP through the processes of electron transport and oxidative phosphorylation, which is used as energy for cardiac contractile function. Mitochondria, in fact, are the key subcellular organelle for the regulation of intracellular Ca²⁺ concentration and are considered to serve as a buffer to maintain Ca²⁺ homeostasis in cardiomyocytes. However, during the development of heart disease, the excessive accumulation of intracellular Ca²⁺ results in mitochondria Ca²⁺-overload, which, in turn, impairs mitochondrial energy production and induces cardiac dysfunction. Mitochondria also generate reactive oxygen species (ROS), including superoxide anion radicals and hydroxyl radicals as well as non-radical oxidants such as hydrogen peroxide, which promote lipid peroxidation and the subsequent disturbance of Ca²⁺ homeostasis, cellular damage, and death. Conclusion: These observations support the view that both oxidative stress and intracellular Ca²⁺-overload play a critical role in mitochondrial disruption during the pathogenesis of different cardiac pathologies. Full article

The inner ear and/or lateral line are responsible for hearing and balance of vertebrate. The otic sensory hair cells (HCs) employ cilium organelles, namely stereocilia and/or kinocilia, to mediate mechanical stimuli to electrical signal transition. Tektins (Tekts) are known as the cilium microtubule stabilizer and inner-space filler, and four Tekt(1-4)-encoding genes are identified in zebrafish HCs, but the subcellular location of Tekts in HCs remains unknown. In the present study, we first found that tekt3 is expressed in the inner ear and lateral line neuromast. Antibody staining revealed that Tekt3 is present in neuromast and utricular HCs. It is absent in the saccule, the authentic hearing end-organ of zebrafish and the crista of semi-circular canals. Furthermore, Tekt3 were enriched at the apical side of neuromast and utricular HCs, mainly in the cytosol. Similar subcellular distribution of Tekt3 was also evident in the outer HCs of mature mouse cochlea, which are not directly linked to the hearing sense. However, only neuromast HCs exerted morphological defect of kinocilia in tekt3 mutant. The disrupted or distorted HC kinocilia of mutant neuromast ultimately resulted in slower vital dye intake, delayed HC regeneration after neomycin treatment, and reduced startle response to vibration stimulation. All functional defects of tekt3 mutant were largely rescued by wild-type tekt3 mRNA. Our study thus suggests that zebrafish Tekt3 maintains the integrity and function of neuromast kinocilia to against surrounding and persistent low-frequency noises, perhaps via the intracellular distribution of Tekt3. Nevertheless, TEKT3/Tekt3 could be used to clarify HC sub-types in both zebrafish and mice, to highlight the non-hearing HCs. Full article

Delayed reperfusion of the ischemic heart (I/R) is known to impair the recovery of cardiac function and produce a wide variety of myocardial defects, including ultrastructural damage, metabolic alterations, subcellular Ca²⁺-handling abnormalities, activation of proteases, and changes in cardiac gene expression. Although I/R injury has been reported to induce the formation of reactive oxygen species (ROS), inflammation, and intracellular Ca²⁺ overload, the generation of oxidative stress is considered to play a critical role in the development of cardiac dysfunction. Increases in the production of superoxide, hydroxyl radicals, and oxidants, such as hydrogen peroxide and hypochlorous acid, occur in hearts subjected to I/R injury. In fact, mitochondria are a major source of the excessive production of ROS in I/R hearts due to impairment in the electron transport system as well as activation of xanthine oxidase and NADPH oxidase. Nitric oxide synthase, mainly present in the endothelium, is also activated due to I/R injury, leading to the production of nitric oxide, which, upon combination with superoxide radicals, generates nitrosative stress. Alterations in cardiac function, sarcolemma, sarcoplasmic reticulum Ca²⁺-handling activities, mitochondrial oxidative phosphorylation, and protease activation due to I/R injury are simulated upon exposing the heart to the oxyradical-generating system (xanthine plus xanthine oxidase) or H₂O₂. On the other hand, the activation of endogenous antioxidants such as superoxide dismutase, catalase, glutathione peroxidase, and the concentration of a transcription factor (Nrf2), which modulates the expression of various endogenous antioxidants, is depressed due to I/R injury in hearts. Furthermore, pretreatment of hearts with antioxidants such as catalase plus superoxide dismutase, N-acetylcysteine, and mercaptopropionylglycerine has been observed to attenuate I/R-induced subcellular Ca²⁺ handling and changes in Ca²⁺-regulatory activities; additionally, it has been found to depress protease activation and improve the recovery of cardiac function. These observations indicate that oxidative stress is intimately involved in the pathological effects of I/R injury and different antioxidants attenuate I/R-induced subcellular alterations and improve the recovery of cardiac function. Thus, we are faced with the task of developing safe and effective antioxidants as well as agents for upregulating the expression of endogenous antioxidants for the therapy of I/R injury. Full article

Passion fruit (Passiflora edulis), mainly distributed in tropical and subtropical regions, is popular for its unique flavor and health benefits. The actin cytoskeleton plays a crucial role in plant growth and development, and villin is a key regulator of actin dynamics. However, the mechanism underlying the actin filament regulation of reproductive development in passion fruit remains poorly understood. Here, we characterized a villin isovariant in passion fruit, Passiflora edulis VLN4 (PeVLN4), highly and preferentially expressed in pollen. Subcellular localization analysis showed that PeVLN4 decorated distinct filamentous structures in pollen tubes. We next introduced PeVLN4 into Arabidopsis villin mutants to explore its functions on the growing pollen tubes. PeVLN4 rescued defects in the elongation of villin mutant pollen tubes. Pollen tubes expressing PeVLN4 were revealed to be less sensitive to latrunculin B, and PeVLN4 partially rescued defects in the actin filament organization of villin mutant pollen tubes. Additionally, biochemical assays revealed that PeVLN4 bundles actin filaments in vitro. Thus, PeVLN4 is an important regulator of F-actin stability and is required for normal pollen tube growth in passion fruit. This study provides a new insight into the function of the actin regulator villin involved in the reproduction development of passion fruit. Full article

Unique genes refer to genes specific to a particular organism and play crucial roles in the biological functions, evolutionary processes, and adaptations to external environments. However, the roles of unique genes in plant pathogenic fungi remain largely unexplored. In this study, we identified a novel unique gene in the rice blast fungus Magnaporthe oryzae, named MoUNG (M. oryzae unique gene), through T-DNA insertion mutagenesis. The disruption of the MoUNG promoter region in the T-DNA insertion mutant (T30-104) led to an almost loss of MoUNG expression. MoUNG has no functional domains and lacks homologues in other organism. It is highly expressed during the early-infection stage between 16 and 32 h post-inoculation (HPI), in contrast to its expression in mycelia and at the later infection stage of 48 HPI. Notably, attempts to knock out MoUNG were unsuccessful, so we examined the T30-104 mutant and found it showed significantly reduced growth, conidiation, and pathogenicity. Introducing the full-length MoUNG with its promoter into T30-104 restored these phenotypic defects. Additionally, subcellular localization assays revealed that MoUNG exhibits a dot-like distribution within the cytoplasm of mycelium, conidium, appressorium, and invasive hypha. Furthermore, knock-down of MoUNG produced results similar to those observed with the insertion mutation. In conclusion, we identified a novel unique gene MoUNG in M. oryzae and demonstrated its involvement in growth, conidiation, and pathogenicity. Full article

Acid invertases (Ac-Invs) are crucial enzymes in plant physiology, regulating sucrose metabolism and hydrolyzing sucrose into glucose and fructose. These sugars serve not only as energy sources and structural components but also as signaling molecules, influencing diverse developmental processes, including seed and fruit growth, flowering, and stress responses. Ac-Invs are classified into cell wall invertases (CWINs) and vacuolar invertases (VINs) based on their subcellular localization, with both playing distinct roles in sucrose unloading, osmotic regulation, and sugar accumulation. Recent studies have also highlighted their involvement in abiotic stress adaptation and hormonal regulation, emphasizing their central role in plant resilience and productivity. However, gaps remain in understanding their regulatory mechanisms, particularly their interactions with plant hormones, defective invertases, and responses to environmental stresses. This review summarizes the biochemical characteristics, functions, and regulatory mechanisms of Ac-Invs, providing insights into their evolutionary significance and potential applications in crop improvement. Future research directions are proposed to elucidate unresolved questions and leverage Ac-Invs for enhancing agricultural sustainability. Full article

Heart failure is a complex syndrome characterized by cardiac hypertrophy, fibrosis, and diastolic/systolic dysfunction. These changes share many pathological features with significant inflammatory responses in the myocardium. Among the various regulatory systems that impact on these heterogeneous pathological processes, angiotensin II (Ang II)-activated macrophages play a pivotal role in the induction of subcellular defects and cardiac adverse remodeling during the progression of heart failure. Ang II stimulates macrophages via its AT1 receptor to release oxygen-free radicals, cytokines, chemokines, and other inflammatory mediators in the myocardium, and upregulates the expression of integrin adhesion molecules on both monocytes and endothelial cells, leading to monocyte-endothelial cell-cell interactions. The transendothelial migration of monocyte-derived macrophages exerts significant biological effects on the proliferation of fibroblasts, deposition of extracellular matrix proteins, induction of perivascular/interstitial fibrosis, and development of hypertension, cardiac hypertrophy and heart failure. Inhibition of macrophage activation using Ang II AT1 receptor antagonist or depletion of macrophages from the peripheral circulation has shown significant inhibitory effects on Ang II-induced vascular and myocardial injury. The purpose of this review is to discuss the current understanding in Ang II-induced maladaptive cardiac remodeling and dysfunction, particularly focusing on molecular signaling pathways involved in macrophages-mediated hypertension, cardiac hypertrophy, fibrosis, and failure. In addition, the challenges remained in translating these findings to the treatment of heart failure patients are also addressed. Full article

The plant-specific IDD transcription factors (TFs) are vital for regulating plant growth and developmental processes. However, the characteristics and biological roles of the IDD gene family in tomato (Solanum lycopersicum) are still largely unexplored. In this study, 17 SlIDD genes were identified in the tomato genome and classified into seven subgroups according to the evolutionary relationships of IDD proteins. Analysis of exon–intron structures and conserved motifs reflected the evolutionary conservation of SlIDDs in tomato. Collinearity analysis revealed that segmental duplication promoted the expansion of the SlIDD family. Ka/Ks analysis indicated that SlIDD gene orthologs experienced predominantly purifying selection throughout evolution. The analysis of cis-acting elements revealed that the promoters of SlIDD genes contain numerous elements associated with light, plant hormones, and abiotic stresses. The RNA-seq data and qRT-PCR experimental results showed that the SlIDD genes exhibited tissue-specific expression. Additionally, Group A members from Arabidopsis thaliana and rice are known to play a role in regulating plant shoot gravitropism. QRT-PCR analysis confirmed that the expression level of SlIDD15 in Group A was high in the hypocotyls and stems. Subcellular localization demonstrated that the SlIDD15 protein was localized in the nucleus. Surprisingly, the loss-of-function of SlIDD15 by CRISPR/Cas9 gene editing technology did not display obvious gravitropic response defects, implying the existence of functional redundant factors within SlIDD15. Taken together, this study offers foundational insights into the tomato IDD gene family and serves as a valuable guide for exploring their molecular mechanisms in greater detail. Full article

Stenotaphrum secundatum is an excellent shade-tolerant warm-season turfgrass. Its poor cold resistance severely limits its promotion and application in temperate regions. Mining cold resistance genes is highly important for the cultivation of cold-resistant Stenotaphrum secundatum. Although there have been many reports on the role of the Shaker potassium channel family under abiotic stress, such as drought and salt stress, there is still a lack of research on their role in cold resistance. In this study, the transcriptome database of Stenotaphrum secundatum was aligned with the whole genome of Setaria italica, and eight members of the Shaker potassium channel family in Stenotaphrum secundatum were identified and named SsKAT1.1, SsKAT1.2, SsKAT2.1, SsKAT2.2, SsAKT1.1, SsAKT2.1, SsAKT2.2, and SsKOR1. The KAT3-like gene, KOR2 homologous gene, and part of the AKT-type weakly inwardly rectifying channel have not been identified in the Stenotaphrum secundatum transcriptome database. A bioinformatics analysis revealed that the potassium channels of Stenotaphrum secundatum are highly conserved in terms of protein structure but have more homologous members in the same group than those of other species. Among the three species of Oryza sativa, Arabidopsis thaliana, and Setaria italica, the potassium channel of Stenotaphrum secundatum is more closely related to the potassium channel of Setaria italica, which is consistent with the taxonomic results of these species belonging to Paniceae. Subcellular location experiments demonstrate that SsKAT1.1 is a plasma membrane protein. The expression of SsKAT1.1 reversed the growth defect of the potassium absorption-deficient yeast strain R5421 under a low potassium supply, indicating that SsKAT1.1 is a functional potassium channel. The transformation of SsKAT1.1 into the cold-sensitive yeast strain INVSC1 increased the cold resistance of the yeast, indicating that SsKAT1.1 confers cold resistance. The transformation of SsKAT1.1 into the salt-sensitive yeast strain G19 increased the resistance of yeast to salt, indicating that SsKAT1.1 is involved in salt tolerance. These results suggest that the manipulation of SsKAT1.1 will improve the cold and salt stress resistance of Stenotaphrum secundatum. Full article

An Arabidopsis sterol mutant, smt2 smt3, defective in sterolmethyltransferase2 (SMT2), exhibits severe growth abnormalities. The loss of C-24 ethyl sterols, maintaining the biosynthesis of C-24 methyl sterols and brassinosteroids, suggests specific roles of C-24 ethyl sterols. We characterized the subcellular localizations of fluorescent protein-fused sterol biosynthetic enzymes, such as SMT2-GFP, and found these enzymes in the endoplasmic reticulum during interphase and identified their movement to the division plane during cytokinesis. The mobilization of endoplasmic reticulum-localized SMT2-GFP was independent of the polarized transport of cytokinetic vesicles to the division plane. In smt2 smt3, SMT2-GFP moved to the abnormal division plane, and unclear cell plate ends were surrounded by hazy structures from SMT2-GFP fluorescent signals and unincorporated cellulose debris. Unusual cortical microtubule organization and impaired cytoskeletal function accompanied the failure to determine the cortical division site and division plane formation. These results indicated that both endoplasmic reticulum membrane remodeling and cytokinetic vesicle transport during cytokinesis were impaired, resulting in the defects of cell wall generation. The cell wall integrity was compromised in the daughter cells, preventing the correct determination of the subsequent cell division site. We discuss the possible roles of C-24 ethyl sterols in the interaction between the cytoskeletal network and the plasma membrane. Full article

In order to investigate the subcellular mechanisms underlying the beneficial effects of sarpogrelate—a 5-HT_2A receptor antagonist—on diabetic cardiomyopathy, diabetes was induced in rats by injecting streptozotocin (65 mg/kg). Diabetic animals were treated with or without sarpogrelate (5 mg/kg daily) for 6 weeks; diabetic animals were also treated with insulin (10 units/kg daily) for comparison. Elevated plasma levels of glucose and lipids, depressed insulin levels, hemodynamic alterations and cardiac dysfunction in diabetic animals were partially or fully attenuated by sarpogrelate or insulin treatment. Diabetes-induced changes in myocardial high-energy phosphate stores, as well as depressed mitochondrial oxidative phosphorylation and Ca²⁺-uptake activities, were significantly prevented by these treatments. Reductions in sarcolemma Na⁺-K⁺ ATPase, Na⁺-Ca²⁺ exchange, Ca²⁺-channel density and Ca²⁺-uptake activities were also attenuated by treatments with sarpogrelate and insulin. In addition, decreases in diabetes-induced sarcoplasmic reticulum Ca²⁺-uptake, Ca²⁺-release and Ca²⁺-stimulated ATPase activities, myofibrillar Mg²⁺-ATPase and Ca²⁺-stimulated ATPase activities, and myosin Mg²⁺-ATPase and Ca²⁺-ATPase activities were fully or partially prevented by sarpogrelate and insulin treatments. Marked alterations in different biomarkers of oxidative stress, such as malondialdehyde, superoxide dismutase and glutathione peroxidase, in diabetic hearts were also attenuated by treating the animals with sarpogrelate or insulin. These observations suggest that therapy with sarpogrelate, like that with insulin, may improve cardiac function by preventing subcellular and metabolic defects as a consequence of a reduction in oxidative stress. Full article

SARS-CoV-2 infection has been recently shown to induce cellular senescence in vivo. A senescence-like phenotype has been reported in cystic fibrosis (CF) cellular models. Since the previously published data highlighted a low impact of SARS-CoV-2 on CFTR-defective cells, here we aimed to investigate the senescence hallmarks in SARS-CoV-2 infection in the context of a loss of CFTR expression/function. We infected WT and CFTR KO 16HBE14o-cells with SARS-CoV-2 and analyzed both the p21 and Ki67 expression using immunohistochemistry and viral and p21 gene expression using real-time PCR. Prior to SARS-CoV-2 infection, CFTR KO cells displayed a higher p21 and lower Ki67 expression than WT cells. We detected lipid accumulation in CFTR KO cells, identified as lipolysosomes and residual bodies at the subcellular/ultrastructure level. After SARS-CoV-2 infection, the situation reversed, with low p21 and high Ki67 expression, as well as reduced viral gene expression in CFTR KO cells. Thus, the activation of cellular senescence pathways in CFTR-defective cells was reversed by SARS-CoV-2 infection while they were activated in CFTR WT cells. These data uncover a different response of CF and non-CF bronchial epithelial cell models to SARS-CoV-2 infection and contribute to uncovering the molecular mechanisms behind the reduced clinical impact of COVID-19 in CF patients. Full article

Heart failure is the common concluding pathway for a majority of cardiovascular diseases and is associated with cardiac dysfunction. Since heart failure is invariably preceded by adaptive or maladaptive cardiac hypertrophy, several biochemical mechanisms have been proposed to explain the development of cardiac hypertrophy and progression to heart failure. One of these includes the activation of different neuroendocrine systems for elevating the circulating levels of different vasoactive hormones such as catecholamines, angiotensin II, vasopressin, serotonin and endothelins. All these hormones are released in the circulation and stimulate different signal transduction systems by acting on their respective receptors on the cell membrane to promote protein synthesis in cardiomyocytes and induce cardiac hypertrophy. The elevated levels of these vasoactive hormones induce hemodynamic overload, increase ventricular wall tension, increase protein synthesis and the occurrence of cardiac remodeling. In addition, there occurs an increase in proinflammatory cytokines and collagen synthesis for the induction of myocardial fibrosis and the transition of adaptive to maladaptive hypertrophy. The prolonged exposure of the hypertrophied heart to these vasoactive hormones has been reported to result in the oxidation of catecholamines and serotonin via monoamine oxidase as well as the activation of NADPH oxidase via angiotensin II and endothelins to promote oxidative stress. The development of oxidative stress produces subcellular defects, Ca²⁺-handling abnormalities, mitochondrial Ca²⁺-overload and cardiac dysfunction by activating different proteases and depressing cardiac gene expression, in addition to destabilizing the extracellular matrix upon activating some metalloproteinases. These observations support the view that elevated levels of various vasoactive hormones, by producing hemodynamic overload and activating their respective receptor-mediated signal transduction mechanisms, induce cardiac hypertrophy. Furthermore, the occurrence of oxidative stress due to the prolonged exposure of the hypertrophied heart to these hormones plays a critical role in the progression of heart failure. Full article

Down syndrome (DS) is the most common form of inherited intellectual disability caused by trisomy of chromosome 21, presenting with intellectual impairment, craniofacial abnormalities, cardiac defects, and gastrointestinal disorders. The Ts65Dn mouse model replicates many abnormalities of DS. We hypothesized that investigation of the cerebral cortex of fluoxetine-treated trisomic mice may provide proteomic signatures that identify therapeutic targets for DS. Subcellular fractionation of synaptosomes from cerebral cortices of age- and brain-area-matched samples from fluoxetine-treated vs. water-treated trisomic and euploid male mice were subjected to HPLC-tandem mass spectrometry. Analysis of the data revealed enrichment of trisomic risk genes that participate in regulation of synaptic vesicular traffic, pre-synaptic and post-synaptic development, and mitochondrial energy pathways during early brain development. Proteomic analysis of trisomic synaptic fractions revealed significant downregulation of proteins involved in synaptic vesicular traffic, including vesicular endocytosis (CLTA, CLTB, CLTC), synaptic assembly and maturation (EXOC1, EXOC3, EXOC8), anterograde axonal transport (EXOC1), neurotransmitter transport to PSD (SACM1L), endosomal-lysosomal acidification (ROGDI, DMXL2), and synaptic signaling (NRXN1, HIP1, ITSN1, YWHAG). Additionally, trisomic proteomes revealed upregulation of several trafficking proteins, involved in vesicular exocytosis (Rab5B), synapse elimination (UBE3A), scission of endocytosis (DBN1), transport of ER in dendritic spines (MYO5A), presynaptic activity-dependent bulk endocytosis (FMR1), and NMDA receptor activity (GRIN2A). Chronic fluoxetine treatment of Ts65Dn mice rescued synaptic vesicular abnormalities and prevented abnormal proteomic changes in adult Ts65Dn mice, pointing to therapeutic targets for potential treatment of DS. Full article

Peptidoglycan hydrolases are enzymes responsible for breaking the peptidoglycan present in the bacterial cell wall, facilitating cell growth, cell division and peptidoglycan turnover. Xanthomonas citri subsp. citri (X. citri), the causal agent of citrus canker, encodes an Escherichia coli M23 peptidase EnvC homolog. EnvC is a LytM factor essential for cleaving the septal peptidoglycan, thereby facilitating the separation of daughter cells. In this study, the investigation focused on EnvC contribution to the virulence and cell separation of X. citri. It was observed that disruption of the X. citri envC gene (ΔenvC) led to a reduction in virulence. Upon inoculation into leaves of Rangpur lime (Citrus limonia Osbeck), the X. citri ΔenvC exhibited a delayed onset of citrus canker symptoms compared with the wild-type X. citri. Mutant complementation restored the wild-type phenotype. Sub-cellular localization confirmed that X. citri EnvC is a periplasmic protein. Moreover, the X. citri ΔenvC mutant exhibited elongated cells, indicating a defect in cell division. These findings support the role of EnvC in the regulation of cell wall organization, cell division, and they clarify the role of this peptidase in X. citri virulence. Full article