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Archives of Biochemistry and Biophysics Jun 2024It has been previously demonstrated that the maintenance of ischemic acidic pH or the delay of intracellular pH recovery at the onset of reperfusion decreases...
BACKGROUND
It has been previously demonstrated that the maintenance of ischemic acidic pH or the delay of intracellular pH recovery at the onset of reperfusion decreases ischemic-induced cardiomyocyte death.
OBJECTIVE
To examine the role played by nitric oxide synthase (NOS)/NO-dependent pathways in the effects of acidic reperfusion in a regional ischemia model METHODS: Isolated rat hearts perfused by Langendorff technique were submitted to 40 min of left coronary artery occlusion followed by 60 min of reperfusion (IC). A group of hearts received an acid solution (pH=6.4) during the first 2 min of reperfusion (AR) in absence or in presence of L-NAME (NOS inhibitor). Infarct size (IS) and myocardial function were determined. In cardiac homogenates, the expression of P-Akt, P-endothelial and inducible isoforms of NOS (P-eNOS and iNOS) and the level of 3-nitrotyrosine were measured. In isolated cardiomyocytes, the intracellular NO production was assessed by confocal microscopy, under control and acidic conditions. Mitochondrial swelling after Ca addition and mitochondrial membrane potential (Δψ) were also determined under control and acidosis RESULTS: AR decreased IS, improved postischemic myocardial function recovery, increased P-Akt and P-eNOS, and decreased iNOS and 3-nitrotyrosine. NO production increased while mitochondrial swelling and Δψ decreased in acidic conditions. L-NAME prevented the beneficial effects of AR CONCLUSIONS: Our data strongly supports that a brief acidic reperfusion protects the myocardium against the ischemia-reperfusion injury through eNOS/NO-dependent pathways.
PubMed: 38936683
DOI: 10.1016/j.abb.2024.110059 -
European Journal of Pharmacology Jun 2024The use of NPS compounds is increasing, and impairment in spatial learning and memory is a growing concern. Alpha-pyrrolidinovalerophenone (α-PVP) consumption, as a...
The use of NPS compounds is increasing, and impairment in spatial learning and memory is a growing concern. Alpha-pyrrolidinovalerophenone (α-PVP) consumption, as a commonly used NPS, can impair spatial learning and memory through brain mitochondrial dysfunction mechanisem. Liraglutide, one of the most well-known Glucagon-like peptide 1 (GLP-1) agonist used as an anti-diabetic and anti-obesity drug. According to current research, Liraglutide likely ameliorate cognitive impairment in neurodegenerative conditions and also substance use disorders. Hence, the purpose of this study is examining the effect of Liraglutide on α-PVP induced spatial learning and memory problems due to brain mitochondrial dysfunction. Wistar rats (8 in each group) received α-PVP (20 mg/kg/d for 10 consecutive days, intraperitoneally (I.P.)). Then, Liraglutide was administered at 47 and 94 μg/kg/d, I.P., for 4 weeks following the α-PVP administration. The Morris Water Maze (MWM) task evaluated spatial learning and memory 24 hours after Liraglutide treatment. Bedside, brain mitochondrial activity parameters including reactive oxygen species (ROS) level, mitochondrial membrane potential (MMP), cytochrome c release, mitochondrial outer membrane damage and swelling, and brain ADP/ATP ratio were studied. Our results showed Liraglutide ameliorated α-PVP induced spatial learning and memory impairments through alleviating brain mitochondrial dysfunctions (which is indicated by increasing ROS formation, collapsed MMP, mitochondrial outer membrane damage, cytochrome c release, mitochondrial swelling, and brain ADP/ATP ratio) in rats. This study could be used as a starting point for future studies about the possible role of Liraglutide in mitochondrial dysfunction related to cognitive impairments due to substance use disorder.
PubMed: 38936451
DOI: 10.1016/j.ejphar.2024.176776 -
Molecular Genetics & Genomic Medicine Jun 2024To further comprehend the phenotype of multiple mitochondrial dysfunction syndrome type 3 (MMDS3:OMIM#615330) caused by IBA57 mutation. We present a case involving a...
OBJECTIVE
To further comprehend the phenotype of multiple mitochondrial dysfunction syndrome type 3 (MMDS3:OMIM#615330) caused by IBA57 mutation. We present a case involving a patient who experienced acute neurological regression, and the literature was reviewed.
METHODS
Clinical data and laboratory test results were collected; early language and development progress were tested; and genetic testing was performed. Bioinformatics analysis was performed using Mutation Taster and PolyPhen-2, and the literature in databases such as PubMed and CNKI was searched using MMDS3 and IBA57 as keywords.
RESULTS
The child, aged 1 year and 2 months, had motor decline, unable to sit alone, limited right arm movement, hypotonia, hyperreflexia of both knees, and Babinski sign positivity on the right side, accompanied by nystagmus. Blood lactate levels were elevated at 2.50 mmol/L. Brain MR indicated slight swelling in the bilateral frontoparietal and occipital white matter areas and the corpus callosum, with extensive abnormal signals on T1 and T2 images, along with the semioval center and occipital lobes bilaterally. The multiple abnormal signals in the brain suggested metabolic leukoencephalopathy. Whole-exome sequencing analysis revealed that the child had two heterozygous mutations in the IBA57 gene, c.286T>C (p.Y96H) (likely pathogenic, LP) and c.992T>A (p.L331Q) (variant of uncertain significance, VUS). As of March 2023, a literature search showed that 56 cases of MMDS3 caused by IBA57 mutation had been reported worldwide, with 35 cases reported in China. Among the 35 IBA57 mutations listed in the HGMD database, there were 28 missense or nonsense mutations, 2 splicing mutations, 2 small deletions, and 3 small insertions.
CONCLUSION
MMDS3 predominantly manifests in infancy, with primary symptoms including feeding difficulties, neurological functional regression, muscle weakness, with severe cases potentially leading to mortality. Diagnosis is supported by elevated lactate levels, multisystem impairment (including auditory and visual systems), and distinctive MRI findings. Whole-exome sequencing is crucial for diagnosis. Currently, cocktail therapy offers symptomatic relief.
Topics: Humans; Infant; Male; Phenotype; Mutation; Female; Microfilament Proteins; Carrier Proteins; Mitochondrial Diseases
PubMed: 38923322
DOI: 10.1002/mgg3.2485 -
Animal Reproduction Science Jun 2024In poultry reproduction, the decline of ovarian function due to aging is related to dysfunction of mitochondria exacerbated by a reduction in antioxidant capacity,...
In poultry reproduction, the decline of ovarian function due to aging is related to dysfunction of mitochondria exacerbated by a reduction in antioxidant capacity, ultimately leading to follicle atresia and decreased egg production. However, the mechanisms of mitochondrial dysfunction in the chicken ovary in aging have remained to be understood. Hence, this study aims to investigate the effects of aging on mitochondrial function and cellular homeostasis. We collect ovarian tissue, small white follicles (SWF), large white follicles (LWF), and small yellow follicles (SYF) from three different laying periods of hens. The transmission electron microscopy (TEM) results showed that mitochondrial damage occurred in ovarian tissue during the late laying period (LP), characterized by structural swelling, scattered mitochondrial cristae, and an increase in the vacuoles. At the same time, with age, the synthesis of steroid hormones in the ovaries and follicular tissues is reduced. The levels of autophagy and cell apoptosis in ovarian tissues were both increased in the LP. In addition, aging adversely impacts mitochondrial function, leading to a decrease in mitochondrial unfolded protein response (UPR) functions. This study will expand the knowledge about regressing ovarian aging in hens and increasing egg production in older layers for poultry production.
PubMed: 38908171
DOI: 10.1016/j.anireprosci.2024.107540 -
Skin Research and Technology : Official... Jun 2024Transient Receptor Potential Mucolipin 1 (TRPML1) serves as a pivotal reactive oxygen species (ROS) sensor in cells, which is implicated in the regulation of autophagy....
BACKGROUND
Transient Receptor Potential Mucolipin 1 (TRPML1) serves as a pivotal reactive oxygen species (ROS) sensor in cells, which is implicated in the regulation of autophagy. However, its function in melanocyte autophagy under oxidative stress remains elusive.
METHODS
The expression and ion channel function of TRPML1 were investigated using immunofluorescence and calcium imaging in primary human melanocytes (MCs). After activating TRPML1 with MLSA1 (TRPML1 agonist), autophagy-related molecules were investigated via western blot. ROS level, apoptosis- and autophagy-related molecules were investigated after pretreatment with MLSA1. After interference with TRPML1 expression, mitochondrial structures were visualized by electron microscopy with hydrogen peroxide (HO)treatment.
RESULTS
TRPML1 was expressed and functionally active in primary human MCs, and its activation promotes elevated expression of LC3-II and reduced apoptosis and ROS levels under oxidative stress. TRPML1 downregulation caused mitochondrial swelling and disruption of cristae structures under oxidative stress in primary human MCs.
CONCLUSIONS
TRPML1 might mediate lysosomal autophagy in primary human MCs under oxidative stress, participating in mechanisms that maintain the oxidative and antioxidant systems in balance.
Topics: Humans; Apoptosis; Autophagy; Calcium; Cells, Cultured; Hydrogen Peroxide; Melanocytes; Mitochondria; Oxidative Stress; Reactive Oxygen Species; Transient Receptor Potential Channels
PubMed: 38899729
DOI: 10.1111/srt.13772 -
Basic Research in Cardiology Jun 2024Mitochondrial calcium (Ca) signals play a central role in cardiac homeostasis and disease. In the healthy heart, mitochondrial Ca levels modulate the rate of oxidative... (Review)
Review
Mitochondrial calcium (Ca) signals play a central role in cardiac homeostasis and disease. In the healthy heart, mitochondrial Ca levels modulate the rate of oxidative metabolism to match the rate of adenosine triphosphate consumption in the cytosol. During ischemia/reperfusion (I/R) injury, pathologically high levels of Ca in the mitochondrial matrix trigger the opening of the mitochondrial permeability transition pore, which releases solutes and small proteins from the matrix, causing mitochondrial swelling and ultimately leading to cell death. Pharmacological and genetic approaches to tune mitochondrial Ca handling by regulating the activity of the main Ca influx and efflux pathways, i.e., the mitochondrial Ca uniporter and sodium/Ca exchanger, represent promising therapeutic strategies to protect the heart from I/R injury.
PubMed: 38890208
DOI: 10.1007/s00395-024-01060-2 -
Applied Microbiology and Biotechnology Jun 2024Obstructive sleep apnea (OSA) can lead to intestinal injury, endotoxemia, and disturbance of intestinal flora. Additionally, as a crucial component of the...
Obstructive sleep apnea (OSA) can lead to intestinal injury, endotoxemia, and disturbance of intestinal flora. Additionally, as a crucial component of the endocannabinoid system, some studies have demonstrated that cannabinoid 1 (CB1) receptors are closely linked to the multiple organ dysfunction triggered by OSA. However, the role of the CB1 receptor in alleviating OSA-induced colon injury remains unclear. Here, through the construction of the OSA classic model, we found that the colon tissue of chronic intermittent hypoxia (CIH)-induced mice exhibited an overexpression of the CB1 receptor. The results of hematoxylin-eosin staining and transmission electron microscopy revealed that inhibition of the CB1 receptor could decrease the gap between the mucosa and muscularis mucosae, alleviate mitochondrial swelling, reduce microvilli shedding, and promote the recovery of tight junctions of CIH-induced mice. Furthermore, CB1 receptor inhibition reduced the levels of metabolic endotoxemia and inflammatory responses, exhibiting significant protective effects on the colon injury caused by CIH. At the molecular level, through western blotting and real-time polymerase chain reaction techniques, we found that inhibiting the CB1 receptor can significantly increase the expression of ZO-1 and Occludin proteins, which are closely related to the maintenance of intestinal mucosal barrier function. Through 16S rRNA high-throughput sequencing and short-chain fatty acid (SCFA) determination, we found that inhibition of the CB1 receptor increased the diversity of the microbial flora and controlled the makeup of intestinal flora. Moreover, butyric acid concentration and the amount of SCFA-producing bacteria, such as Ruminococcaceae and Lachnospiraceae, were both markedly elevated by CB1 receptor inhibition. The results of the spearman correlation study indicated that Lachnospiraceae showed a positive association with both ZO-1 and Occludin but was negatively correlated with the colon CB1 receptor, IL-1β, and TNF-α. According to this study, we found that inhibiting CB1 receptor can improve CIH-induced colon injury by regulating gut microbiota, reducing mucosal damage and promoting tight junction recovery. KEY POINTS: •CIH leads to overexpression of CB1 receptor in colon tissue. •CIH causes intestinal flora disorder, intestinal mucosal damage, and disruption of tight junctions. •Inhibition of CB1 receptor can alleviate the colon injury caused by CIH through regulating the gut microbiota, reducing mucosal injury, and promoting tight junction recovery.
Topics: Animals; Receptor, Cannabinoid, CB1; Mice; Disease Models, Animal; Colon; Male; Intestinal Mucosa; Hypoxia; Mice, Inbred C57BL; Zonula Occludens-1 Protein; Occludin; Gastrointestinal Microbiome; Tight Junctions
PubMed: 38888634
DOI: 10.1007/s00253-024-13216-0 -
BMC Plant Biology Jun 2024Seed aging, a natural and inevitable process occurring during storage. Oats, an annual herb belonging to the Gramineae family and pooideae. In addition to being a...
Cytological structures and physiological and biochemical characteristics of covered oat (Avena sativa L.) and naked oat (Avena nuda L.) seeds during high-temperature artificial aging.
BACKGROUND
Seed aging, a natural and inevitable process occurring during storage. Oats, an annual herb belonging to the Gramineae family and pooideae. In addition to being a healthy food, oats serve as ecological pastures, combating soil salinization and desertification. They also play a role in promoting grassland agriculture and supplementing winter livestock feed. However, the high lipid and fat derivatives contents of oat seeds make them susceptible to deterioration, as fat derivatives are prone to rancidity, affecting oat seed production, storage, development, and germplasm resource utilization. Comparative studies on the effects of aging on physiology and cytological structure in covered and naked oat seeds are limited. Thus, our study aimed to determine the mechanism underlying seed deterioration in artificially aged 'LongYan No. 3' (A. sativa) and 'BaiYan No. 2' (A. nuda) seeds, providing a basis for the physiological evaluation of oat seed aging and serving as a reference for scientifically safe storage and efficient utilization of oats.
RESULTS
In both oat varieties, superoxide dismutase and catalase activities in seeds showed increasing and decreasing trends, respectively. Variance analysis revealed significant differences and interaction in all measured indicators of oat seeds between the two varieties at different aging times. 'LongYan No. 3' seeds, aged for 24-96 h, exhibited a germination rate of < 30%, Conductivity, malondialdehyde, soluble sugar, and soluble protein levels increased more significantly than the 'BaiYan No. 2'. With prolonged aging leading to cell membrane degradation, reactive oxygen species accumulation, disrupted antioxidant enzyme system, evident embryo cell swelling, and disordered cell arrangement, blocking the nutrient supply route. Simultaneously, severely concentrated chromatin in the nucleus, damaged mitochondrial structure, and impaired energy metabolism were noted, resulting in the loss of 'LongYan No. 3' seed vitality and value. Conversely, 'BaiYan No. 2' seeds showed a germination rate of 73.33% after 96 h of aging, consistently higher antioxidant enzyme activity during aging, normal embryonic cell shape, and existence of the endoplasmic reticulum.
CONCLUSIONS
ROS accumulation and antioxidant enzyme system damage in aged oat seeds, nuclear chromatin condensation, mitochondrial structure damage, nucleic acid metabolism and respiration weakened, oat seed vigor decreased. 'LongYan No. 3' seeds were more severely damaged under artificial aging than 'BaiYan No. 2' seeds, highlighting their heightened susceptibility to aging effects.
Topics: Avena; Seeds; Hot Temperature; Catalase; Superoxide Dismutase; Germination; Antioxidants
PubMed: 38862888
DOI: 10.1186/s12870-024-05221-2 -
Theranostics 2024Gouty arthritis causes severe pain and inflammation. Alginate oligosaccharides (AOSs) are natural products derived from alginate and have anti-inflammatory properties....
Gouty arthritis causes severe pain and inflammation. Alginate oligosaccharides (AOSs) are natural products derived from alginate and have anti-inflammatory properties. We explored the potential effects of AOSs with different degrees of polymerization (Dp) on gouty arthritis and associated mechanisms. We established a mouse model of gouty arthritis by injecting monosodium urate (MSU) into ankle joint. Nocifensive behavior, gait and ankle swelling were used to study AOS's effects. Biochemical assays, imaging, live cell Ca imaging, electrophysiology, RNA-sequencing, etc. were used for mechanism exploration. AOS2 (Dp=2), AOS3 (Dp=3) and AOS4 (Dp=4) all inhibited ankle swelling, whereas AOS2&3 produced the most obvious analgesia on model mice. AOS3, which was picked for further evaluation, produced dose-dependent ameliorative effects on model mice. AOS3 reversed gait impairments but did not alter locomotor activity. AOS3 inhibited NLRP3 inflammasome activation and inflammatory cytokine up-regulation in ankle joint. AOS3 ameliorated MSU-induced oxidative stress and reactive oxygen species (ROS) production both and and reversed the impaired mitochondrial bioenergetics. AOS3 activated the Nrf2 pathway and promoted Nrf2 disassociation from Keap1-bound complex and Nrf2 nuclear translocation, thus facilitating antioxidant gene expression via Nrf2-dependent mechanism. gene deficiency abolished AOS3's ameliorative effects on pain, inflammation and oxidative stress in ankle joints of model mice. AOS3 reduced TRPV1 functional enhancement in DRG neurons and constrained neuroactive peptide release. AOS3 ameliorates gouty arthritis via activating Nrf2-dependent antioxidant signaling, resulting in suppression of ROS-mediated NLRP3 inflammasome activation and TRPV1 enhancement. AOS3 may be novel therapeutics for gouty arthritis.
Topics: Animals; Arthritis, Gouty; Mice; Oligosaccharides; Disease Models, Animal; Alginates; Inflammation; NLR Family, Pyrin Domain-Containing 3 Protein; Male; Arthralgia; Uric Acid; Mice, Inbred C57BL; Anti-Inflammatory Agents; Inflammasomes; Ankle Joint; NF-E2-Related Factor 2; Oxidative Stress
PubMed: 38855180
DOI: 10.7150/thno.95611 -
Biochemistry and Cell Biology =... Jun 2024Altered mitochondrial structure and function are implicated in the functional decline of skeletal muscle. Numerous cytoskeletal proteins are known to affect...
Altered mitochondrial structure and function are implicated in the functional decline of skeletal muscle. Numerous cytoskeletal proteins are known to affect mitochondrial homeostasis, but this complex network is still being unraveled. Here, we investigated mitochondrial alterations in mice lacking the cytoskeletal adapter protein, XIN (XIN-/-). XIN-/- and wild-type littermate male and female mice were fed a chow or high-fat diet (HFD; 60% kcal fat) for 8 weeks before analyses of their skeletal muscles was conducted. Immuno-electron microscopy (EM) and immunofluorescence staining revealed XIN in the mitochondria and peri-mitochondrial areas, as well as the myoplasm. Intermyofibrillar mitochondria in chow-fed XIN-/- mice were notably different from wild-type (large, and/or swollen in appearance). Succinate Dehydrogenase and Cytochrome Oxidase IV staining indicated greater evidence of mitochondrial enzyme activity in XIN-/- mice. No difference in body mass gains or glucose handling was observed between cohorts with HFD. However, EM revealed significantly greater mitochondrial density with evident structural abnormalities (swelling, reduced cristae density) in XIN-/- mice. Absolute Complex I and II-supported respiration was not different between groups, but relative to mitochondrial density, was significantly lower in XIN-/-. These results provide the first evidence for a role of XIN in maintaining mitochondrial morphology and function.
PubMed: 38843556
DOI: 10.1139/bcb-2024-0034