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1.
Plant Physiol Biochem ; 207: 108420, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38324953

RESUMO

Cyclic electron transport (CET) around photosystem I (PSI) mediated by the NADH dehydrogenase-like (NDH) complex is closely related to plant salt tolerance. However, whether overexpression of a core subunit of the NDH complex affects the photosynthetic electron transport under salt stress is currently unclear. Here, we expressed the NDH complex L subunit (Ndhl) genes ZmNdhl1 and ZmNdhl2 from C4 plant maize (Zea mays) or OsNdhl from C3 plant rice (Oryza sativa) using a constitutive promoter in rice. Transgenic rice lines expressing ZmNdhl1, ZmNdhl2, or OsNdhl displayed enhanced salt tolerance, as indicated by greater plant height, dry weight, and leaf relative water content, as well as lower malondialdehyde content compared to wild-type plants under salt stress. Fluorescence parameters such as post-illumination rise (PIR), the prompt chlorophyll a fluorescence transient (OJIP), modulated 820-nm reflection (MR), and delayed chlorophyll a fluorescence (DF) remained relatively normal in transgenic plants during salt stress. These results indicate that expression of ZmNdhl1, ZmNdhl2, or OsNdhl increases cyclic electron transport activity, slows down damage to linear electron transport, alleviates oxidative damage to the PSI reaction center and plastocyanin, and reduces damage to electron transport on the receptor side of PSI in rice leaves under salt stress. Thus, expression of Ndhl genes from maize or rice improves salt tolerance by enhancing photosynthetic electron transport in rice. Maize and rice Ndhl genes played a similar role in enhancing salinity tolerance and avoiding photosynthetic damage.


Assuntos
Oryza , Tolerância ao Sal , Transporte de Elétrons , Tolerância ao Sal/genética , Clorofila A/metabolismo , NADH Desidrogenase/genética , NADH Desidrogenase/metabolismo , Fotossíntese , Complexo de Proteína do Fotossistema I/metabolismo , Oryza/genética , Oryza/metabolismo
2.
PLoS One ; 19(1): e0297166, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38285689

RESUMO

Src is a non-receptor tyrosine kinase participating in a range of neuronal processes, including synaptic plasticity. We have recently shown that the amounts of total Src and its two phosphorylated forms, at tyrosine-416 (activated) and tyrosine-527 (inhibited), undergoes time-dependent, region-specific learning-related changes in the domestic chick forebrain after visual imprinting. These changes occur in the intermediate medial mesopallium (IMM), a site of memory formation for visual imprinting, but not the posterior pole of the nidopallium (PPN), a control brain region not involved in imprinting. Src interacts with mitochondrial genome-coded NADH dehydrogenase subunit 2 (NADH2), a component of mitochondrial respiratory complex I. This interaction occurs at brain excitatory synapses bearing NMDA glutamate receptors. The involvement of Src-NADH2 complexes in learning and memory is not yet explored. We show for the first time that, independently of changes in total Src or total NADH2, NADH2 bound to Src immunoprecipitated from the P2 plasma membrane-mitochondrial fraction: (i) is increased in a learning-related manner in the left IMM 1 h after the end of training; (ii), is decreased in the right IMM in a learning-related way 24 h after training. These changes occurred in the IMM but not the PPN. They are attributable to learning occurring during training rather than a predisposition to learn. Learning-related changes in Src-bound NADH2 are thus time- and region-dependent.


Assuntos
Fixação Psicológica Instintiva , NADH Desidrogenase , Quinases da Família src , Animais , Galinhas , Fixação Psicológica Instintiva/fisiologia , Aprendizagem/fisiologia , Prosencéfalo/fisiologia , Tirosina , Quinases da Família src/metabolismo
3.
J Cancer Res Clin Oncol ; 150(1): 8, 2024 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-38195952

RESUMO

BACKGROUND: NUDT21 (Nudix Hydrolase 21) has been shown to play an essential role in multiple biological processes. Pancreatic adenocarcinoma (PAAD) is one of the most fatal cancers in the world. However, the biological function of NUDT21 in PAAD remains rarely understood. The aim of this research was to identify the prediction value of NUDT21 in diagnosis, prognosis, immune infiltration, and signal pathway in PAAD. METHODS: Combined with the data in online databases, we analyzed the expression, immune infiltration, function enrichment, signal pathway, diagnosis, and prognosis of NUDT21 in PAAD. Then, the biological function of NUDT21 and its interacted protein in PAAD was identified through plasmid transduction system and protein mass spectrometry. Expression of NUDT21 was further verified in clinical specimens by immunofluorescence. RESULTS: We found that NUDT21 was upregulated in PAAD tissues and was significantly associated with the diagnosis and prognosis of pancreatic cancer through bioinformatic data analysis. We also found that overexpression of NUDT21 enhanced PAAD cells proliferation and migration, whereas knockdown NUDT21 restored the effects through in vitro experiment. Moreover, NDUFS2 was recognized as a potential target of NUDT21.We further verified that the expression of NDUFS2 was positively correlated with NUDT21 in PAAD clinical specimens. Mechanically, we found that NUDT21 stabilizes NDUFS2 and activates the PI3K-AKT signaling pathway. CONCLUSION: Our investigation reveals that NUDT21 is a previously unrecognized oncogenic factor in the diagnosis, prognosis, and treatment target of PAAD, and we suggest that NUDT21 might be a novel therapeutic target in PAAD.


Assuntos
Adenocarcinoma , Fator de Especificidade de Clivagem e Poliadenilação , NADH Desidrogenase , Neoplasias Pancreáticas , Humanos , Adenocarcinoma/genética , Proliferação de Células , NADH Desidrogenase/genética , Neoplasias Pancreáticas/genética , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Fator de Especificidade de Clivagem e Poliadenilação/genética
4.
Acta Trop ; 252: 107124, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38262573

RESUMO

Cystic echinococcosis (CE) is a common zoonotic disease caused by the larval form of Echinococcus granulosus sensu lato. This study determined the genotype and haplotype differences using the NADH dehydrogenase subunit 5 gene in hydatid cyst samples. Human (n = 12), cattle (n = 28), and sheep (n = 31) hydatid cyst isolates were included. Seventy-one genomic DNA samples were successfully extracted, and a 759 bp mitochondrial NADH dehydrogenase subunit 5 gene fragment was amplified by PCR. Following the sequence analysis, E. granulosus sensu stricto isolates were identified as G1 (n = 61) and G3 (n = 10). A total of 23 haplotypes were obtained from the 71 E. granulosus s.s. G1 and G3 samples. The main haplotype was Hap01 (60.56 %), which consisted of the G1 genotype. The second largest haplotype was Hap04, which consisted entirely of the G3 genotype. Hap14 acted as a bridge between the G1 and G3 genotypes. This study identifies G1 as the dominant genotype in humans and farm animals in Turkey. High haplotype and nucleotide diversity in genotypes were observed. Additionally, this is the first report on the phylogeography and gene flow models of the E. granulosus s.s. population in Turkey using the NADH dehydrogenase subunit 5 gene, the best marker distinguishing between G1 and G3 genotypes.


Assuntos
Equinococose , Echinococcus granulosus , Echinococcus , Humanos , Animais , Bovinos , Ovinos , Echinococcus granulosus/genética , NADH Desidrogenase/genética , Equinococose/veterinária , Equinococose/epidemiologia , Echinococcus/genética , Genótipo
5.
EMBO J ; 43(2): 225-249, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38177503

RESUMO

Respiratory complex I (NADH:ubiquinone oxidoreductase) is essential for cellular energy production and NAD+ homeostasis. Complex I mutations cause neuromuscular, mitochondrial diseases, such as Leigh Syndrome, but their molecular-level consequences remain poorly understood. Here, we use a popular complex I-linked mitochondrial disease model, the ndufs4-/- mouse, to define the structural, biochemical, and functional consequences of the absence of subunit NDUFS4. Cryo-EM analyses of the complex I from ndufs4-/- mouse hearts revealed a loose association of the NADH-dehydrogenase module, and discrete classes containing either assembly factor NDUFAF2 or subunit NDUFS6. Subunit NDUFA12, which replaces its paralogue NDUFAF2 in mature complex I, is absent from all classes, compounding the deletion of NDUFS4 and preventing maturation of an NDUFS4-free enzyme. We propose that NDUFAF2 recruits the NADH-dehydrogenase module during assembly of the complex. Taken together, the findings provide new molecular-level understanding of the ndufs4-/- mouse model and complex I-linked mitochondrial disease.


Assuntos
Doença de Leigh , Doenças Mitocondriais , Animais , Camundongos , Complexo I de Transporte de Elétrons/genética , Complexo I de Transporte de Elétrons/metabolismo , Doença de Leigh/genética , Mitocôndrias/metabolismo , Doenças Mitocondriais/genética , NAD/metabolismo , NADH Desidrogenase/genética , NADH Desidrogenase/metabolismo
6.
Heart Surg Forum ; 27(1): E028-E037, 2024 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-38286648

RESUMO

BACKGROUND: This study mainly investigated the mechanism and effects of AKAP1 in renal patients with acute heart failure (AHF). METHODS: Patients with renal patients with AHF and normal volunteers were collected. The left anterior descending arteries (LAD) of mice were ligated to induce myocardial infarction. RESULTS: AKAP1 messenger RNA (mRNA) expression was found to be down-regulated in renal patients with AHF. The serum levels of AKAP1 mRNA expression were negatively correlated with collagen I/III in patients. AKAP1 mRNA and protein expression in the heart tissue of mice with AHF were also found to be down-regulated in a time-dependent manner. Short hairpin (Sh)-AKAP1 promotes AHF in a mouse model. AKAP1 up-regulation reduces reactive oxygen species (ROS)-induced oxidative stress in an In Vitro model. AKAP1 up-regulation also reduces ROS-induced lipid peroxidation ferroptosis in an In Vitro model. AKAP1 induces NDUFS1 expression to increase GPX4 activity levels. AKAP1 protein interlinked with the NDUFS1 protein. Up-regulation of the AKAP1 gene reduced NDUFS1 ubiquitination, while down-regulation of the AKAP1 gene increased NDUFS1 ubiquitination in a model. In vivo imaging showed that the sh-AKAP1 virus reduced NDUFS1 expression in the heart of a mouse model. CONCLUSIONS: AKAP1 reduced ROS-induced lipid peroxidation ferroptosis through the inhibition of ubiquitination of NDUFS by mitochondrial damage in model of renal patients with AHF, suggest a novel target for AHF treatment.


Assuntos
Proteínas de Ancoragem à Quinase A , Ferroptose , Insuficiência Cardíaca , Animais , Humanos , Camundongos , Insuficiência Cardíaca/genética , Miócitos Cardíacos/metabolismo , Espécies Reativas de Oxigênio/metabolismo , RNA Mensageiro , Proteínas de Ancoragem à Quinase A/metabolismo , NADH Desidrogenase/metabolismo
7.
Free Radic Biol Med ; 213: 79-89, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38242247

RESUMO

Abnormal mitochondrial function has been implicated in the progression of systemic lupus erythematosus (SLE), the prototypical autoimmune disease, yet the underlying cause remains unclear. In this study, mitochondrial-encoded NADH dehydrogenase 6 gene (MT-ND6) was identified as having increased m6A methylation and decreased expression in peripheral blood mononuclear cells of SLE patients by MeRIP-seq analysis. MT-ND6 expression was negatively correlated with SLE disease activity index score and 24-h urine protein level, and lower in patients with positive anti-Sm or anti-dsDNA antibodies. With the reduction of MT-ND6 levels, CD4+ T cells in SLE patients exhibited mitochondrial dysfunction, as evidenced by increased levels of reactive oxygen species (ROS) and mitochondrial ROS and insufficient ATP production. Accordingly, in vitro MT-ND6 silencing induced abnormalities in the above mitochondrial indicators in CD4+ T cells, and promoted the development of both transcription and inflammatory factors in these cells. In contrast, treatment with targeted mitochondrial antioxidants largely counteracted the silencing effect of MT-MD6. Thus, reduced MT-ND6 in SLE patients may lead to mitochondrial dysfunction through ROS overproduction, thereby promoting inflammatory CD4+ T cells.


Assuntos
Lúpus Eritematoso Sistêmico , Doenças Mitocondriais , Humanos , Expressão Gênica , Leucócitos Mononucleares , Lúpus Eritematoso Sistêmico/genética , NADH Desidrogenase/genética , Espécies Reativas de Oxigênio , Linfócitos T
8.
Parasitol Res ; 123(1): 113, 2024 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-38273031

RESUMO

Prohemistomum vivax is a zoonotic small cyathocotylid trematode that inhabits the intestines of fish-eating birds and mammals. Here, we amplified the internal transcribed spacer (ITS) sequence and six mitochondrial protein-coding genes (PCGs) from P. vivax. The ITS region was 1389 base pairs long and had a partial 18S ribosomal RNA gene, a full ITS1, 5.8S rRNA, and ITS2 sequence, and a partial 28S rRNA gene. The ITS region of P. vivax showed a minimum pairwise distance (0.3-0.6%) from the ITS sequences of Cyathocotylidae sp. 1 and 2 metacercariae from Clarias gariepinus. This result suggests that these metacercariae belong to P. vivax metacercariae. We first amplified mitochondrial genes from P. vivax, including cytochrome c oxidase subunit III (cox3) partial sequence; tRNA-His, cytochrome b (cytb), and NADH dehydrogenase subunit 4L (nad4L) complete sequences; and NADH dehydrogenase subunit 4 (nad4), cytochrome c oxidase I (cox1), and NADH dehydrogenase subunit 5 (nad5) partial sequences. P. vivax was most closely related to Cyathocotyle prussica (NC_039780) and Holostephanus sp. (OP082179), with cox1, cox3, and cytb genes conserved among the three trematodes. The ML phylogenetic tree of ITS sequences supports the order Diplostomida, divided into two main clades (the superfamily Diplostomoidea and Schistosomatoidea). The phylogeny of concatenated amino acid sequences of P. vivax six PCGs revealed that diplostomoids and Clinostomum sp. evolved in a clade with Plagiorchiida members, away from Schistosoma species. These results may yield ribosomal and mitochondrial genetic markers for molecular epidemiological investigations of cyathocotylid intestinal flukes.


Assuntos
Genes Mitocondriais , Trematódeos , Animais , Filogenia , NADH Desidrogenase/genética , Trematódeos/genética , RNA Ribossômico 28S/genética , Mamíferos
9.
J Neuromuscul Dis ; 11(2): 485-491, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38217609

RESUMO

Background: The NADH dehydrogenase [ubiquinone] iron-sulfur protein 6 (NDUFS6) gene encodes for an accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (complex I). Bi-allelic NDUFS6 variants have been linked with a severe disorder mostly reported as a lethal infantile mitochondrial disease (LMID) or Leigh syndrome (LS). Objective: Here, we identified a homozygous variant (c.309 + 5 G > A) in NDUFS6 in one male patient with axonal neuropathy accompanied by loss of small fibers in skin biopsy and further complicated by optic atrophy and borderline intellectual disability. Methods: To address the pathogenicity of the variant, biochemical studies (mtDNA copy number quantification, ELISA, Proteomic profiling) of patient-derived leukocytes were performed. Results: The analyses revealed loss of NDUFS6 protein associated with a decrease of three further mitochondrial NADH dehydrogenase subunit/assembly proteins (NDUFA12, NDUFS4 and NDUFV1). Mitochondrial copy number is not altered in leukocytes and the mitochondrial biomarker GDF15 is not significantly changed in serum. Conclusions: Hence, our combined clinical and biochemical data strengthen the concept of NDUFS6 being causative for a very rare form of axonal neuropathy associated with optic atrophy and borderline intellectual disability, and thus expand (i) the molecular genetic landscape of neuropathies and (ii) the clinical spectrum of NDUFS6-associated phenotypes.


Assuntos
Deficiência Intelectual , Atrofia Óptica , Humanos , Masculino , Complexo I de Transporte de Elétrons/genética , Complexo I de Transporte de Elétrons/metabolismo , NADH Desidrogenase/genética , NADH Desidrogenase/metabolismo , NADPH Desidrogenase/metabolismo , Atrofia Óptica/genética , Proteômica
10.
Bioresour Technol ; 393: 130027, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37977496

RESUMO

Bioconversion of CO2 to high-valuable products is a globally pursued sustainable technology for carbon neutrality. However, low CO2 activation with formate dehydrogenase (FDH) remains a major challenge for further upcycling due to the poor CO2 affinity, reduction activity and stability of currently used FDHs. Here, we present two recombined mutants, ΔFDHPa48 and ΔFDHPa4814, which exhibit high CO2 reduction activity and antioxidative activity. Compared to FDHPa, the reduction activity of ΔFDHPa48 was increased up to 743 % and the yield in the reduction of CO2 to methanol was increased by 3.16-fold. Molecular dynamics identified that increasing the width of the substrate pocket of ΔFDHPa48 could improve the enzyme reduction activity. Meanwhile, the enhanced rigidity of C-terminal residues effectively protected the active center. These results fundamentally advanced our understanding of the CO2 activation process and efficient FDH for enzymatic CO2 activation and conversion.


Assuntos
Dióxido de Carbono , Formiato Desidrogenases , Dióxido de Carbono/metabolismo , Formiato Desidrogenases/genética , NAD/metabolismo , NADH Desidrogenase , Oxirredução , Formiatos/química
11.
Biochem Biophys Res Commun ; 693: 149374, 2024 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-38096616

RESUMO

Cervical cancer, a common malignancy in women, poses a significant health burden worldwide. In this study, we aimed to investigate the expression, function, and potential mechanisms of NADH: ubiquinone oxidoreductase subunit A8 (NDUFA8) in cervical cancer. The Gene Expression Profiling Interactive Analysis (GEPIA) database and immunohistochemical scoring were used to analyze NDUFA8 expression in cervical cancer tissues and normal tissues. Quantitative real-time PCR and Western blot analyses were performed to assess the expression level of NDUFA8 in cervical cancer cell lines. NDUFA8 knockdown or overexpression experiments were conducted to evaluate its impact on cell proliferation and apoptosis. The mitochondrial respiratory status was analyzed by measuring cellular oxygen consumption, adenosine triphosphate (ATP) levels, and the expression levels of Mitochondrial Complex I activity, and Mitochondrial Complex IV-associated proteins Cytochrome C Oxidase Subunit 5B (COX5B) and COX6C. NDUFA8 exhibited high expression levels in cervical cancer tissues, and these levels were correlated with reduced survival rates. A significant upregulation of NDUFA8 expression was observed in cervical cancer cell lines compared to normal cells. Silencing NDUFA8 hindered cell proliferation, promoted apoptosis, and concurrently suppressed cellular mitochondrial respiration, resulting in decreased levels of available ATP. Conversely, NDUFA8 overexpression induced the opposite effects. Herein, we also found that E1A Binding Protein P300 (EP300) overexpression facilitated Histone H3 Lysine 27 (H3K27) acetylation enrichment, enhancing the activity of the NDUFA8 promoter region. NDUFA8, which is highly expressed in cervical cancer, is regulated by transcriptional control via EP300/H3K27 acetylation. By promoting mitochondrial respiration, NDUFA8 contributes to cervical cancer cell proliferation and apoptosis. These findings provide novel insights into NDUFA8 as a therapeutic target in cervical cancer.


Assuntos
Neoplasias do Colo do Útero , Humanos , Feminino , Neoplasias do Colo do Útero/patologia , Fatores de Transcrição/metabolismo , Complexo I de Transporte de Elétrons/genética , Complexo I de Transporte de Elétrons/metabolismo , Apoptose/genética , Proliferação de Células/genética , Respiração , Trifosfato de Adenosina , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , NADH Desidrogenase/genética , NADH Desidrogenase/metabolismo , Proteína p300 Associada a E1A/genética , Proteína p300 Associada a E1A/metabolismo
12.
New Phytol ; 241(1): 82-101, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37872738

RESUMO

C4 plants typically operate a CO2 concentration mechanism from mesophyll (M) cells into bundle sheath (BS) cells. NADH dehydrogenase-like (NDH) complex is enriched in the BS cells of many NADP-malic enzyme (ME) type C4 plants and is more abundant in C4 than in C3 plants, but to what extent it is involved in the CO2 concentration mechanism remains to be experimentally investigated. We created maize and rice mutants deficient in NDH function and then used a combination of transcriptomic, proteomic, and metabolomic approaches for comparative analysis. Considerable decreases in growth, photosynthetic activities, and levels of key photosynthetic proteins were observed in maize but not rice mutants. However, transcript abundance for many cyclic electron transport (CET) and Calvin-Benson cycle components, as well as BS-specific C4 enzymes, was increased in maize mutants. Metabolite analysis of the maize ndh mutants revealed an increased NADPH : NADP ratio, as well as malate, ribulose 1,5-bisphosphate (RuBP), fructose 1,6-bisphosphate (FBP), and photorespiration intermediates. We suggest that by optimizing NADPH and malate levels and adjusting NADP-ME activity, NDH functions to balance metabolic and redox states in the BS cells of maize (in addition to ATP supply), coordinating photosynthetic transcript abundance and protein content, thus directly regulating the carbon flow in the two-celled C4 system of maize.


Assuntos
Carbono , NADH Desidrogenase , Carbono/metabolismo , NADH Desidrogenase/metabolismo , Zea mays/genética , Zea mays/metabolismo , Malatos/metabolismo , NADP/metabolismo , Dióxido de Carbono/metabolismo , Proteômica , Fotossíntese , Oxirredução , Malato Desidrogenase/genética , Malato Desidrogenase/metabolismo , Folhas de Planta/metabolismo
13.
Medicine (Baltimore) ; 102(46): e36133, 2023 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-37986300

RESUMO

Atherosclerosis is a chronic disease that thickens the blood vessel walls and narrows the lumen. Venous thrombosis is a blood clot that forms in the body's deep veins or pulmonary arteries. However, the relationship between NDUFB11 and NDUFS3 and atherosclerosis and venous thrombosis is unclear. We employed data files that combined atherosclerosis and chronic stress groups. Subsequently, we conducted differential gene expression analysis (DEGs) and performed weighted gene co-expression network analysis (WGCNA). We constructed and analyzed a protein-protein interaction (PPI) network. Further analyses included functional enrichment analysis, gene set enrichment analysis (GSEA), gene expression heatmaps, immune infiltration analysis, and mRNA analysis. By comparing our findings with the Comparative Toxicogenomics Database (CTD), we identified the most relevant diseases associated with the core genes. Additionally, we utilized TargetScan to screen for miRNAs regulating the central DEGs. To validate our results, we conducted Western Blot experiments at the cellular level. A total of 1747 DEGs were co-identified. According to the Gene Ontology (GO) analysis of differentially expressed genes, they were primarily enriched in mitochondrial gene expression, mitochondrial envelope, organelle membrane, and mitochondrial inner membrane categories. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that the target cells were mainly enriched in metabolic pathways, ribosomes, and histidine metabolism. The intersection of enriched terms from both GO and KEGG analyses showed significant enrichment in mitochondrial gene expression, mitochondrial envelope, organelle inner membrane, ribosomal structural constituents, histidine metabolism, and oxidative phosphorylation. Eight core genes were identified, including NDUFS5, UQCRQ, COX6C, COX7B, ATP5ME, NDUFS3, NDUFA3, and NDUFB11. The gene expression heatmap demonstrated that core genes (NDUFB11 and NDUFS3) were downregulated in atherosclerosis with venous thrombosis samples and upregulated in normal samples. CTD analysis revealed that the core genes NDUFB11 and NDUFS3 were associated with pain, arterial diseases, atherosclerosis, arteritis, venous thrombosis formation, and venous thromboembolism. We added Western Blot basic cell experiment for verification. NDUFB11 and NDUFS3 are downregulated in atherosclerosis and venous thrombosis, associated with poorer prognosis, and may serve as potential biomarkers for both diseases.


Assuntos
Aterosclerose , MicroRNAs , Trombose Venosa , Humanos , Histidina , Trombose Venosa/genética , Artéria Pulmonar , Perfilação da Expressão Gênica , Aterosclerose/genética , Biologia Computacional , NADH Desidrogenase , Complexo I de Transporte de Elétrons/genética
14.
Microbiol Spectr ; 11(6): e0222523, 2023 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-37855642

RESUMO

IMPORTANCE: Energy generation pathways are a potential avenue for the development of novel antibiotics. However, bacteria possess remarkable resilience due to the compensatory pathways, which presents a challenge in this direction. NADH, the primary reducing equivalent, can transfer electrons to two distinct types of NADH dehydrogenases. Type I NADH dehydrogenase is an enzyme complex comprising multiple subunits and can generate proton motive force (PMF). Type II NADH dehydrogenase does not pump protons but plays a crucial role in maintaining the turnover of NAD+. To study the adaptive rewiring of energy metabolism, we evolved an Escherichia coli mutant lacking type II NADH dehydrogenase. We discovered that by modifying the flux through the tricarboxylic acid (TCA) cycle, E. coli could mitigate the growth impairment observed in the absence of type II NADH dehydrogenase. This research provides valuable insights into the intricate mechanisms employed by bacteria to compensate for disruptions in energy metabolism.


Assuntos
NADH Desidrogenase , Bombas de Próton , NADH Desidrogenase/genética , NADH Desidrogenase/metabolismo , Bombas de Próton/metabolismo , Escherichia coli/metabolismo , Prótons , NAD/metabolismo , Bactérias/metabolismo
15.
Inflammopharmacology ; 31(6): 2955-2971, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37843641

RESUMO

Traumatic brain injury (TBI) is a type of brain injury resulting from a sudden physical force to the head. TBI can range from mild, such as a concussion, to severe, which might result in long-term complications or even death. The initial impact or primary injury to the brain is followed by neuroinflammation, excitotoxicity, and oxidative stress, which are the hallmarks of the secondary injury phase, that can further damage the brain tissue. Dexamethasone (DXM) has neuroprotective effects. It reduces neuroinflammation, a critical factor in secondary injury-associated neuronal damage. DXM can also suppress the microglia activation and infiltrated macrophages, which are responsible for producing pro-inflammatory cytokines that contribute to neuroinflammation. Considering the outcomes of this research, some of the effects of DXM on TBI include: (1) DXM-loaded hydrogels reduce apoptosis, neuroinflammation, and lesion volume and improves neuronal cell survival and motor performance, (2) DXM treatment elevates the levels of Ndufs2, Gria3, MAOB, and Ndufv2 in the hippocampus following TBI, (3) DXM decreases the quantity of circulating endothelial progenitor cells, (4) DXM reduces the expression of IL1, (5) DXM suppresses the infiltration of RhoA + cells into primary lesions of TBI and (6) DXM treatment led to an increase in fractional anisotropy values and a decrease in apparent diffusion coefficient values, indicating improved white matter integrity. According to the study, the findings show that DXM treatment has neuroprotective effects in TBI. This indicates that DXM is a promising therapeutic approach to treating TBI.


Assuntos
Lesões Encefálicas Traumáticas , Fármacos Neuroprotetores , Animais , Camundongos , Doenças Neuroinflamatórias , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Lesões Encefálicas Traumáticas/tratamento farmacológico , Inflamação/metabolismo , Dexametasona/farmacologia , Modelos Animais de Doenças , Microglia , Camundongos Endogâmicos C57BL , NADH Desidrogenase/metabolismo , NADH Desidrogenase/farmacologia , NADH Desidrogenase/uso terapêutico
16.
Neurotoxicology ; 99: 162-176, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37838251

RESUMO

Trimethyltin chloride (TMT) is a potent neurotoxin widely used as a constituent of polyvinyl chloride plastic in the industrial and agricultural fields. However, the underlying mechanisms by which TMT leads to neurotoxicity remain elusive. In the present study, we constructed a dose and time dependent neurotoxic mouse model of TMT exposure to explore the molecular mechanisms involved in TMT-induced neurological damage. Based on this model, the cognitive ability of TMT exposed mice was assessed by the Morris water maze test and a passive avoidance task. The ultrastructure of hippocampus was analyzed by the transmission electron microscope. Subsequently, proteomics integrated with bioinformatics and experimental verification were employed to reveal potential mechanisms of TMT-induced neurotoxicity. Gene ontology (GO) and pathway enrichment analysis were done by using Metascape and GeneCards database respectively. Our results demonstrated that TMT-exposed mice exhibited cognitive disorder, and mitochondrial respiratory chain abnormality of the hippocampus. Proteomics data showed that a total of 7303 proteins were identified in hippocampus of mice of which 224 ones displayed a 1.5-fold increase or decrease in TMT exposed mice compared with controls. Further analysis indicated that these proteins were mainly involved in tricarboxylic acid (TCA) cycle and respiratory electron transport, proteasome degradation, and multiple metabolic pathways as well as inflammatory signaling pathways. Some proteins, including succinate-CoA ligase subunit (Suclg1), NADH dehydrogenase subunit 5 (Nd5), NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 4-like 2 (Ndufa4l2) and cytochrome c oxidase assembly factor 7 (Coa7), which were closely related to mitochondrial respiratory electron transport, showed TMT dose and time dependent changes in the hippocampus of mice. Moreover, apoptotic molecules Bax and cleaved caspase-3 were up-regulated, while anti-apoptotic Bcl-2 was down-regulated compared with controls. In conclusion, our findings suggest that impairment of mitochondrial respiratory chain transport and promotion of apoptosis are the potential mechanisms of TMT induced hippocampus toxicity in mice.


Assuntos
Síndromes Neurotóxicas , Compostos de Trimetilestanho , Camundongos , Animais , Proteômica , NADH Desidrogenase/metabolismo , Compostos de Trimetilestanho/toxicidade , Compostos de Trimetilestanho/metabolismo , Mitocôndrias/metabolismo , Síndromes Neurotóxicas/etiologia , Síndromes Neurotóxicas/metabolismo , Hipocampo/metabolismo
17.
Front Endocrinol (Lausanne) ; 14: 1093353, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37674615

RESUMO

Introduction: Polycystic Ovarian Syndrome (PCOS) is a globally prevalent condition that leads to infertility in women. While environmental factors contribute to PCOS, maternal genetics also play a significant role. Currently, there is no definitive test for identifying predisposition to PCOS. Hence, our objective is to discover novel maternal genetic risk factors for PCOS by investigating the genomes of patients from Pakistan. Methods: We utilized Next-Generation Sequencing (NGS) to sequence the complete mitochondrial DNA of three PCOS patients. Subsequently, we employed MitoTIP (Mitochondrial tRNA Informatics Predictor) and PON-mt-tRNA tools to identify variations in the mitochondrial DNA. Our analysis focused on the genes MT-RNR1, MT-RNR2, MT-ATP6, MT-TL2, and MT-CYTB, which displayed common variations in all three genomes. Additionally, we observed individual variations. The D-loop region exhibited the highest frequency of mutations, followed by the non-coding regions of RNR1 and RNR2 genes. Moreover, we detected frameshift mutations in the mitochondrially encoded NADH Dehydrogenase 2 (MT-ND2) and mitochondrially encoded NADH Dehydrogenase 5 (ND5) genes within individual genomes. Results: Our analysis unveiled six regions with common variations in the mitochondrial DNA of all three PCOS patients. Notably, the MT-RNR1, MT-RNR2, MT-ATP6, MT-TL2, and MT-CYTB genes exhibited these variations. Additionally, we identified individual variations in the mitochondrial DNA. The D-loop region displayed the highest mutation frequency, followed by the non-coding regions of RNR1 and RNR2 genes. Furthermore, frameshift mutations were detected in the MT-ND2 and ND5 genes within individual genomes. Conclusion: Through our study, we have identified variations in mitochondrial DNA that may be associated with the development of PCOS and have the potential to serve as predisposition tests. Our findings highlight the presence of novel mutations in the MT-RNR1, MT-RNR2, MT-ATP6, MT-TL2, and MT-CYTB genes, as well as frameshift mutations in the MT-ND2 and ND5 genes. Pathogenicity analysis indicated that most variants were likely to result in benign cysts. However, the frameshift mutations in the ND2 gene were associated with a high risk of complications and pathogenicity in PCOS. This is the first report identifying these mutations and their association with PCOS, contributing to our understanding of the genetic factors underlying the condition.


Assuntos
DNA Mitocondrial , Síndrome do Ovário Policístico , Humanos , Feminino , DNA Mitocondrial/genética , Herança Materna , NADH Desidrogenase , Síndrome do Ovário Policístico/genética , Mitocôndrias
18.
Plant Signal Behav ; 18(1): 2258321, 2023 12 31.
Artigo em Inglês | MEDLINE | ID: mdl-37707988

RESUMO

The chloroplasts in terrestrial plants play a functional role as a major sensor for perceiving physiological changes under normal and stressful conditions. Despite the fact that the plant chloroplast genome encodes around 120 genes, which are mainly essential for photosynthesis and chloroplast biogenesis, the functional roles of the genes remain to be determined in plant's response to environmental stresses. Photosynthetic electron transfer D (PETD) is a key component of the chloroplast cytochrome b6f complex. Chloroplast ndhA (NADH dehydrogenase A) and ndhB (NADH dehydrogenase B) interact with photosystem I (PSI), forming NDH-PSI supercomplex. Notably, artificial targeting of chloroplasts-encoded proteins, PETD, NDHA, or NDHB, was successfully relocated from cytosols into chloroplasts. The result suggests that artificial targeting of proteins to chloroplasts is potentially open to the possibility of chloroplast biotechnology in engineering of plant tolerance against biotic and abiotic stresses.


Assuntos
Proteínas de Cloroplastos , Complexo Citocromos b6f , Citosol , Proteínas de Cloroplastos/genética , NADH Desidrogenase , Cloroplastos
19.
Cell Death Dis ; 14(8): 512, 2023 08 09.
Artigo em Inglês | MEDLINE | ID: mdl-37558663

RESUMO

Epigenetic modifications play important roles during the pathogenesis of multiple myeloma (MM). Herein, we found that protein arginine methyltransferase 1 (PRMT1) was highly expressed in MM patients, which was positively correlated with MM stages. High PRMT1 expression was correlated with adverse prognosis in MM patients. We further showed that silencing PRMT1 inhibited MM proliferation and tumorigenesis in vitro and in vivo. Mechanistically, we revealed that the knockdown of PRMT1 reduced the oxidative phosphorylation (OXPHOS) of MM cells through NDUFS6 downregulation. Meanwhile, we identified that WTAP, a key component of the m6A methyltransferase complex, was methylated by PRMT1, and NDUFS6 was identified as a bona fide m6A target of WTAP. Finally, we found that the combination of PRMT1 inhibitor and bortezomib synergistically inhibited MM progression. Collectively, our results demonstrate that PRMT1 plays a crucial role during MM tumorigenesis and suggeste that PRMT1 could be a potential therapeutic target in MM.


Assuntos
Mieloma Múltiplo , Fosforilação Oxidativa , Humanos , Metilação , Mieloma Múltiplo/genética , Proteína-Arginina N-Metiltransferases/genética , Proteína-Arginina N-Metiltransferases/metabolismo , Transformação Celular Neoplásica , Carcinogênese/genética , Proteínas Repressoras/metabolismo , Fatores de Processamento de RNA/metabolismo , Proteínas de Ciclo Celular/metabolismo , NADH Desidrogenase/metabolismo
20.
Leg Med (Tokyo) ; 65: 102302, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37549592

RESUMO

Identification of mechanical asphyxia deaths without obvious injuries is a difficult problem for forensic medicine. This study aimed to identify molecular biological markers to predict death from mechanical asphyxia (smother). We established a smother model of mice by over the head with plastic bag tightly until the mice died and applied label-free proteomic technology to identify differentially expressed proteins (DEPs) in heart. A total of 3307 proteins were quantified, and a Fold Change (FC) > 1.2 (or <1/1.2) and Q value < 0.05 were considered as DEPs. Through comparative analysis, we identified 606 DEPs compared to the control group, comprising 219 upregulated and 387 downregulated proteins. Bioinformatics analysis (MCODE analysis) showed that the candidate proteins were mainly involved in regulation of ribosome function, myocardial contraction and calcium regulation, regulation of coagulation and regulation of mitochondrial oxidative respiration. Seven of these proteins were validated using parallel reaction monitoring (PRM), including fibrinogen alpha chain (FIBA), fibrinogen gamma chain (FIBG), Calsequestrin-2 (CASQ2), NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 11 (NDUAB), NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 3 (NDUA3), NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 13 (NDUAD) and Rab7 (RAB7A). CASQ2 and FIBG were further validated by immunohistochemistry. In conclusion, our results may provide some auxiliary indices for identifying the death from mechanical asphyxia.


Assuntos
Asfixia , Proteômica , Camundongos , Animais , Proteômica/métodos , NADH Desidrogenase , Ubiquinona , Biomarcadores , Fibrinogênio
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