- |||||||||| dichloroacetate topical / Generic mfg., doxycycline / Generic mfg., tetracycline / Generic mfg.
Preclinical, Journal: Inducible and reversible SOD2 knockdown in mouse skeletal muscle drives impaired pyruvate oxidation and reduced metabolic flexibility. (Pubmed Central) - Nov 18, 2024
We use a model of inducible and reversible skeletal muscle SOD2 knockdown to demonstrate that elevated matrix superoxide reversibly impairs mitochondrial substrate flexibility characterized by impaired pyruvate oxidation. Despite the bioenergetic effect, the limited change in gene expression suggests that the elevated redox stress in this model is confined to the mitochondrial matrix.
- |||||||||| Journal, Epigenetic controller: Histone deacetylase SlHDA7 impacts fruit ripening and shelf life in tomato. (Pubmed Central) - Nov 7, 2024
Moreover, SlHDA7 suppresses fruit ripening by targeting specific ripening-associated transcription factors (TFs) like RIN, FUL1, and ERF.E1, ultimately leading to delayed ripening and prolonged fruit shelf life. In summary, our findings indicate that SlHDA7 negatively modulates tomato fruit maturation by adjusting H4ac levels of these ripening-associated genes and key TFs.
- |||||||||| iron dextran / Generic mfg.
Uncoupling Alas2 from Iron-Regulatory Proteins Demonstrates the Protective Role of Alas2 Iron-Responsive Element in Protoporphyrias (Halls G-H (San Diego Convention Center)) - Nov 6, 2024 - Abstract #ASH2024ASH_4768;
However, only the Alas2 mutants (XLPP, Alas2?LOOP) see a modest but prolonged increase in erythroid PPIX when injected once with iron dextran...Altogether, our results confirm that iron status strongly modifies the erythroid PPIX accumulation, particularly when Alas2 expression is uncoupled from the IRPs control. We also demonstrated that the IRE-IRP system plays a critical role in mitigating the severity of protoporphyria in the rodents, providing evidence that targeting the Alas2-IRE may have pharmacological benefits.
- |||||||||| Venclexta (venetoclax) / Roche, AbbVie
Riboflavin Drives Nucleotide Biosynthesis and Iron-Sulfur Metabolism to Promote Acute Myeloid Leukemia (Seaport Ballroom ABCD (Manchester Grand Hyatt San Diego)) - Nov 6, 2024 - Abstract #ASH2024ASH_2227;
Collectively, this work describes a mechanistic framework of riboflavin dependency in AML and defines a previously unappreciated interplay between riboflavin and pyrimidine biosynthesis and Fe-S metabolism. Dietary modulation of riboflavin in combination with venetoclax is being tested for anti-leukemic potential in vivo.
- |||||||||| Journal: Binding of ?-synuclein to ACO2 promotes progressive mitochondrial dysfunction in Parkinson's disease models. (Pubmed Central) - Nov 4, 2024
Furthermore, we designed an interfering peptide to block the interaction between ACO2 and h?-syn, which showed therapeutic effects in reducing h?-syn toxicity in vitro and in vivo. Our research establishes a direct link between ?-syn and the TCA cycle and identifies ACO2 as a promising therapeutic target for improving mitochondrial function and reducing ?-syn neurotoxicity in PD.
- |||||||||| Journal: Interactions between Brassinosteroids and Strigolactones in Alleviating Salt Stress in Maize. (Pubmed Central) - Oct 16, 2024
Respective KOG notes concerned inorganic ion transport and metabolism, signal transduction mechanisms, energy production and conversion, and amino acid transport and metabolism. The findings of this study provide a foundation for the proposition that BR and SL can be employed to regulate salt stress alleviation in maize.
- |||||||||| MK-3795 / Merck (MSD)
IRON REGULATORY PROTEIN 2 CONTRIBUTES TO ANTIMICROBIAL IMMUNITY BY PRESERVING LYSOSOMAL FUNCTION IN MACROPHAGES () - Oct 15, 2024 - Abstract #AASLD2024AASLD_1748;
Tfeb mislocalization was reversed by Hif2 inhibitor PT2385 and, independently, through the inhibition of lactic acid production...Tfeb mislocalization was reversed by Hif2 inhibitor PT2385 and, independently, through the inhibition of lactic acid production. Our study highlights a mechanism whereby IRP2 preserves macrophage lysosomal function in antimicrobial activity to protect the liver against gut-originated bacterial invasion, shedding light on therapeutic intervention for patients with PLA.
- |||||||||| dichloroacetate topical / Generic mfg., doxycycline / Generic mfg., tetracycline / Generic mfg.
Preclinical, Journal: Inducible and reversible SOD2 knockdown in mouse skeletal muscle drives impaired pyruvate oxidation and reduced metabolic flexibility. (Pubmed Central) - Oct 10, 2024
We use a model of inducible and reversible skeletal muscle SOD2 knockdown to demonstrate that elevated matrix superoxide reversibly impairs mitochondrial substrate flexibility characterized by impaired pyruvate oxidation. Despite the bioenergetic effect, the limited change in gene expression suggests that the elevated redox stress in this model is confined to the mitochondrial matrix.
- |||||||||| Review, Journal: Mitochondrial Aconitase and Its Contribution to the Pathogenesis of Neurodegenerative Diseases. (Pubmed Central) - Sep 29, 2024
Inactivation or dysfunction of Aco2 as well as mutations found in the ACO2 gene appear to be significant factors in the development and promotion of various types of neurodegenerative diseases. A restoration of efficient mitochondrial functioning as a source of energy for the cell by targeting Aco2 seems to be one of the promising therapeutic directions to minimize progressive neurodegenerative disorders.
- |||||||||| Journal: Impact of singular versus combinatorial environmental stress on RONS generation in Drosophila melanogaster larvae. (Pubmed Central) - Sep 25, 2024
Focusing on the impact of singular versus combinatorial stress exposure on RONS generation, we observed an increase in the RONS level in both singular and combinatorial forms of stress exposure although the magnitude of the increment varied with the nature of stressors and their combinations. The present study indicated an "additive" effect when all three stressors (D + H + S) operate simultaneously, rather than a "synergistic" effect.
- |||||||||| Oxidative Stress-Induced Suppression of Metabolism Pathways in Dahl Salt-Sensitive Rats (Exhibit Hall, Convention Center) - Sep 23, 2024 - Abstract #KIDNEYWEEK2024KIDNEY_WEEK_1256;
Carbon metabolism and amino acid synthesis related genes were suppressed in OM in SS which could functionally lead to lactate accumulation and eventually renal damage as energy demand increased with HS. These changes appear to be driven by increased oxidative stress given the absence of such changes in the SSNox4-/- and SD rats.
- |||||||||| Elucidating the role of iron regulatory protein 2 in the peripheral system (MCP Room S103) - Aug 22, 2024 - Abstract #Neuroscience2024Neuroscience_2907;
These axons rely on extrinsic support from their surrounding Schwann cells (SCs). This minisymposium will focus on the latest advancements in the emerging concept of metabolic communication between axons and SCs as a determinant of nerve integrity under physiological and neurodegenerative conditions.
- |||||||||| Review, Journal: Intracellular peroxynitrite perturbs redox balance, bioenergetics, and Fe-S cluster homeostasis in Mycobacterium tuberculosis. (Pubmed Central) - Aug 21, 2024
Work with Mtb strains defective in SUF and IscS involved in Fe-S cluster biogenesis pathways showed that both systems cooperatively protect Mtb from intracellular ONOO- in vitro and inducible nitric oxide synthase (iNOS)-dependent growth inhibition during macrophage infection. Thus, Mtb is uniquely sensitive to intracellular ONOO- and targeting Fe-S cluster homeostasis is expected to promote iNOS-dependent host immunity against tuberculosis (TB).
- |||||||||| Journal: Isobavachalcone: a redox antifungal agent impairs the mitochondria protein of Cryptococcus neoformans. (Pubmed Central) - Aug 4, 2024
Molecular docking, quantitative polymerase chain reaction experiments, target inhibitor and agonist intervention, molecular interaction measurements, and MIC detection of the constructed expression strains revealed that IBC targeted the activity of these two enzymes, interfered by the tricarboxylic acid cycle, inhibited the production of ATP, blocked electron transport, reduced mitochondrial membrane potential, and induced antioxidation imbalance and reactive oxygen species accumulation, thus producing an antifungal effect. Therefore, IBC is a promising lead drug and redox antifungal agent for C. neoformans.
- |||||||||| Journal: Concept of Normativity in Multi-Omics Analysis of Axon Regeneration. (Pubmed Central) - Jul 31, 2024
As normalized protein amounts are different in different biological states (control versus axon regeneration), normative metabolite or lipid amounts are expected to be different for specific biological states. These concepts and standardization approaches are important for the integration of different datasets across different models of axon regeneration.
- |||||||||| MK-3795 / Merck (MSD)
Journal: Iron regulatory protein 2 contributes to antimicrobial immunity by preserving lysosomal function in macrophages. (Pubmed Central) - Jul 26, 2024
These experimental findings were confirmed clinically in patients with Crohn's disease and through bioinformatic searches in databases from Crohn's disease or ulcerative colitis biopsies showing loss of IRP2 and transcription factor EB (TFEB)-dependent lysosomal gene expression. Overall, our study highlights a mechanism whereby Irp2 supports nuclear translocation of Tfeb and lysosomal function, preserving macrophage antimicrobial activity and protecting the liver against invading bacteria during intestinal inflammation.
- |||||||||| Journal: Unveiling novel targets in melanoma under melanogenesis stimulation and photodynamic therapy by redox proteomics. (Pubmed Central) - Jul 4, 2024
Besides that, glyceraldehyde-3-phosphate dehydrogenase (Gapdh) presented oxidation at Cys-245, peptidyl-prolyl cis-trans isomerase A (Ppia) was oxidized at Cys-161 and 5,6-dihydroxyindole-2-carboxylic acid oxidase (Tyrp1) was oxidized at Cys-65, Cys-30, and Cys-336 after melanogenesis stimulation followed by RB-PDT. The redox alterations observed in murine melanoma cells and identification of possible target proteins are of great importance to further understand tumor resistance mechanisms.
- |||||||||| Journal: Lack of Mitochondrial DNA Provides Metabolic Advantage in Yeast Osmoadaptation. (Pubmed Central) - Jun 27, 2024
Interestingly, selected TCA cycle genes, CIT1 and ACO1, whose expression depends on RTG signaling upon stress, showed a different regulation in ?0 and ?RIM2 cells. These data suggest that osmoadaptation can occur through different mechanisms in the presence of mitochondrial defects and will allow us to gain insight into the relationships among metabolism, mitochondria-mediated stress response, and cell adaptation.
- |||||||||| Review, Journal: Investigating hormesis, aging, and neurodegeneration: From bench to clinics. (Pubmed Central) - Jun 24, 2024
We highlight the potential therapeutic importance of nutritional polyphenols as substantive regulators of the Nrf2 pathway. Here, we discuss the common mechanisms targeting the Nrf2/vitagene pathway, as novel therapeutic strategies to minimize consequences of oxidative stress and neuroinflammation, generally associated to cognitive dysfunction, and demonstrate its key neuroprotective and anti-neuroinflammatory properties, summarizing pharmacotherapeutic aspects relevant to brain pathophysiology.
- |||||||||| Journal: Comparative Proteomic Analysis of Ridge Gourd Seed (Luffa acutangula (L.) Roxb.) during Artificial Aging. (Pubmed Central) - Jun 17, 2024
This study also presented the involvement of aconitase and glutathione pathway-associated enzymes in seed aging, with aconitase and total glutathione being determined as possible suggestive biomarkers for aged ridge gourd seeds. This acquired knowledge has the potential to considerably improve growing methods and seed preservation techniques, enhancing seed storage and maintenance.
- |||||||||| deferoxamine / Generic mfg.
Preclinical, Journal: Iron accumulation in ovarian microenvironment damages the local redox balance and oocyte quality in aging mice. (Pubmed Central) - Jun 12, 2024
These alterations could be phenocopied with in vitro Fe2+ administration in oocytes from 2-month-old mice but were alleviated by deferoxamine (DFO)...Together, our findings suggest that aging-related disturbance in ovarian iron homeostasis contributes to excessive ROS production and that iron chelation may improve ovarian redox status, and efficiently delay the decline in ovarian reserve and oocyte quality in aging mice. These data propose a novel intervention strategy for preserving the ovarian reserve function in elderly women.
- |||||||||| Journal: Functional mechanism (Pubmed Central) - Jun 11, 2024
These data propose a novel intervention strategy for preserving the ovarian reserve function in elderly women. Finally, in silico binding analyses identify a range of highly potent ethylene inhibitors
- |||||||||| Journal: (Pubmed Central) - Jun 5, 2024
This narrow concentration range of responses is ?-cell selective, as the actions of nitric oxide in non-?-cells (?-cells, mouse embryonic fibroblasts, and macrophages) are concentration-dependent. Our findings suggest that ?-cells respond to a narrow concentration range of nitric oxide that is consistent with the levels produced following iNOS induction, and that these concentration-dependent actions are selective for insulin-containing cells.
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