Elevated concentrations of amyloid‐β oligomers and their proapoptotic effects on age‐related cataract

The FASEB Journal, Journal Year: 2024, Volume and Issue: 38(17)

Published: Sept. 1, 2024

Abstract Recently, amyloid‐β oligomers (AβOs) have been studied as the primary pathogenic substances in Alzheimer's disease (AD). Our previous study revealed that Aβ expression level is closely related to ARC progression. Here, we demonstrated accumulation of AβOs lens epithelium age‐related cataract (ARC) patients increased during progression and this alteration was consistent with changes mitochondrial function, oxidative stress, cellular apoptosis. In vitro, human epithelial cells (HLECs) treated exhibited Ca 2+ dyshomeostasis, impaired elevated stress levels, Moreover, proapoptotic effect alleviated after uptake inhibited. These results establish may promote HLEC apoptosis by inducing overload, thus preliminarily revealing possible association between other pathological processes ARC.

Language: Английский

---

Whole genome regulatory effect of MoISW2 and consequences for the evolution of the rice plant pathogenic fungus Magnaporthe oryzae

mBio, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 18, 2024

ABSTRACT Isw2 proteins, ubiquitous across eukaryotes, exhibit a propensity for DNA binding and exert dynamic influences on local chromosome condensation in an ATP-dependent fashion, thereby modulating the accessibility of neighboring genes to transcriptional machinery. Here, we report deletion putative MoISW2 gene, yielding substantial ramifications plant pathogenicity. Subsequent gene complementation chromatin immunoprecipitation sequencing (ChIP-seq) analyses were conducted delineate sites. RNA (RNA-seq) assays revealed discernible impacts global regulation along chromosomes both mutant wild-type strains, with comparative against 55 external RNA-seq data sets corroborating these findings. Notably, MoIsw2-mediated activities genomic loci characterized by pronounced expression variability proximal MoIsw2 sites, juxtaposed comparatively stable surrounding regions. The contingent influenced activity predominantly encompass niche-determinant genes, including those encoding secreted secondary metabolites, stress-responsive elements, alongside avirulence genes. Furthermore, our investigations unveil spatial correlation between motifs known transposable elements (TEs), suggesting potential interplay wherein TE transposition at could modulate landscape Magnaporthe oryzae strain-specific manner. Collectively, findings position as plausible master regulator orchestrating delicate equilibrium vital biomass proliferation, akin housekeeping niche-specific determinants crucial ecological adaptability. Stress-induced transposition, conjunction activity, emerges mechanism fostering enhanced mutagenesis accelerated evolution relative counterparts. IMPORTANCE proteins are conserved plants, fungi, animals, other eukaryotes. We show that fungal protein rice pathogen binds retrotransposon (RT) affects epigenetic genome. Mainly niche determinant close affected. RT occur frequently most organisms. They move place multiply genome, especially under physiological stress. further discuss combined possible sought-after can cause biased mutation rates faster necessary reacting abiotic biotic challenges. important challenges pathogens ones from host plants’ innate immunity. overall result will be adaptation-directed

Language: Английский

---

Increased mitochondrial mutation heteroplasmy induces aging phenotypes in pluripotent stem cells and their differentiated progeny

Aging Cell, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 16, 2024

Abstract The mitochondrial genome (mtDNA) is an important source of inherited extranuclear variation. Clonal increases in mtDNA mutation heteroplasmy have been implicated aging and disease, although the impact this shift on cell function challenging to assess. Reprogramming pluripotency affects heteroplasmy. We reprogrammed three human fibroblast lines with known for deleterious point or deletion mutations. Quantification resulting 76 induced pluripotent stem (iPSC) clones yielded a bimodal distribution, creating sets high levels absent matched nuclear genomes. iPSC elevated show altered growth dynamics, which persist iPSC‐derived progenitor cells. identify transcriptomic metabolic shifts consistent increased investment neutral lipid synthesis as well epigenetic age iPSC, changes occurring cellular aging. Together, these data demonstrate that induces

Language: Английский

---

Highly Selective MIF Ketonase Inhibitor KRP-6 Diminishes M1 Macrophage Polarization and Metabolic Reprogramming

Antioxidants, Journal Year: 2023, Volume and Issue: 12(10), P. 1790 - 1790

Published: Sept. 22, 2023

Macrophage polarization is highly involved in autoimmunity. M1 polarized macrophages drive inflammation and undergo metabolic reprogramming, involving downregulation of mitochondrial energy production acceleration glycolysis. migration inhibitory factor (MIF), an enigmatic tautomerase (ketonase enolase), was discovered to regulate polarization. Here, we reveal that KRP-6, a potent selective MIF ketonase inhibitor, reduces MIF-induced human blood eosinophil neutrophil similarly ISO-1, the most investigated inhibitor. We equally KRP-6 prevents macrophage ROS IFN-γ-treated cells. During improved bioenergetics by ameliorating basal respiration, ATP production, coupling efficiency maximal respiration LPS+IFN-γ-treated also reduced glycolytic flux macrophages. Moreover, inhibitor attenuated LPS+IFN-γ-induced PARP-1 PARP-2 mRNA expression. conclude represents promising novel therapeutic compound for autoimmune diseases, which strongly involves

Language: Английский

---

Metabolic reprogramming of the inflammatory response in the nervous system: the crossover between inflammation and metabolism

Neural Regeneration Research, Journal Year: 2023, Volume and Issue: 19(10), P. 2189 - 2201

Published: Dec. 21, 2023

Metabolism is a fundamental process by which biochemicals are broken down to produce energy (catabolism) or used build macromolecules (anabolism). has received renewed attention as mechanism that generates molecules modulate multiple cellular responses. This was first identified in cancer cells the Warburg effect, but it also present immunocompetent cells. Studies have revealed bidirectional influence of metabolism and immune cell function, highlighting significance metabolic reprogramming activation effector functions. Metabolic processes such glycolysis, oxidative phosphorylation, fatty acid oxidation been shown undergo dynamic changes during response, facilitating energetic biosynthetic demands. review aims provide better understanding occurs different upon activation, with special focus on central nervous system disorders. Understanding response not only provides insights into mechanisms regulate function opens new approaches for therapeutic strategies aimed at manipulating system.

Language: Английский

---