Idebenone Protects Photoreceptors Impaired by Oxidative Phosphorylation Disorder in Retinal Detachment

Investigative Ophthalmology & Visual Science, Journal Year: 2025, Volume and Issue: 66(1), P. 17 - 17

Published: Jan. 8, 2025

Purpose: Oxidative phosphorylation (OXPHOS) is an aerobic metabolic mechanism, and its dysfunction plays important role in the pathological changes of ischemic diseases. However, systematic studies on occurrence retinal detachment (RD) are lacking. Methods: Single-cell RNA sequencing (scRNA-seq) human retina was performed to detect various cells after RD. In this study, animal experiments were conducted explore OXPHOS activity addition, idebenone, a coenzyme Q10 (CoQ10) analog currently used treat Leber hereditary optic neuropathy (LHON), improve disorder experimental RD model. Results: ScRNA-seq revealed abnormal energy metabolism pathways Adenosine triphosphate (ATP) reactive oxygen species (ROS) main products OXPHOS, mouse model indicated that rise ROS levels may have greater impact photoreceptors early stage, whereas decreased ATP synthesis observed later stage; these threaten function morphology retina. Idebenone administered mice intragastrically, leading reduced stage post-RD improved which closely related maintenance mitochondrial morphology. Conclusions: leads photoreceptor degeneration RD, can be alleviated by improving function.

Language: Английский

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High fructose levels inhibit the proliferation of cardiomyocytes via the Notch1 signaling pathway

Cellular Signalling, Journal Year: 2025, Volume and Issue: 127, P. 111600 - 111600

Published: Jan. 9, 2025

Language: Английский

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Discovery of 15-deoxynaphthomycins activating the antioxidant NRF2-ARE pathway from Streptomyces sp. N50 via genome mining, global regulator introduction, and molecular networking

Microbial Cell Factories, Journal Year: 2025, Volume and Issue: 24(1)

Published: Jan. 10, 2025

Genome mining is a promising avenue for expanding the repertoire of microbial natural products, which are important drug development. This approach involves predicting genetically encoded small molecules by examining bacterial genomes via accumulated knowledge biosynthesis. However, it also that microbes produce predicted molecule in practice. Here, we introduce an endophytic Streptomyces sp. N50, was isolated from medicinal plant Selaginella tamariscina. Upon sequencing its entire genome, 33 biosynthetic gene clusters (BGCs) were identified chromosome and megaplasmid. Subsequent genome revealed new 15-deoxynaphthomycin could be produced due to presence enoyl reductase domain, absent known BGC naphthomycin, type ansamycin antibiotics. In addition, engineered strain with introduction global regulatory afsR2 into N50 successfully 15-deoxynaphthomycins. Furthermore, molecular network analysis MS/MS selectively confirmed additional sulfur-containing congeners. Eventually, six 15-deoxynaphthomycins elucidated N50. family compounds exhibit various biological activities. Also, quinone moieties these compounds, activate NRF2, they tested their ability NRF2. Among three (1, 5, 6) activated antioxidant NRF2-ARE signaling pathway. Treatment significantly elevated NRF2 levels HepG2 cells further induced expression target genes associated response. study suggests combination mining, engineering networking helpful generating as pharmaceutical candidates microorganisms.

Language: Английский

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The total extract of Abelmoschus manihot (L.) medic flowers (TEA) mediated Nrf2-TFAM signalling to regulate mitochondrial antioxidant mechanism

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: Jan. 10, 2025

Abstract Skin, as the first line of defence human body, is exposed to dangers such overheating substances, ultraviolet rays, and environmental pollutants, incidence skin diseases increasing annually. Oxidative stress plays a dominant role in most diseases. Abelmoschus manihot (L.) medic flower (TEA) traditional Chinese medicine widely used treat injuries water fire scalds. It has been reported that TEA excellent antioxidant effects. In this study, we aimed explore mitochondrial protection effects H 2 O -mediated HaCaT cell damage. cells were incubated with simulate oxidative skin. The effect on was also evaluated. Cell morphology observed via inverted microscopy, viability measured MTT reagent. stained Hoechst 33,324 solution. Reactive oxygen species (ROS), superoxide dismutase (SOD), malondialdehyde (MDA) ATP detection kits detect corresponding indicators. membrane potential detected by JC-1. RT-PCR mRNA mtDNA expression. expression target protein Western blotting immunofluorescence. triggered damage cells, which manifested apoptosis, increased ROS MDA contents, decreased SOD activity. activates KEAP1/Nrf2/NQO1 signalling pathway, decreases intracellular KEAP1 slightly increases Nrf2 NQO1 proteins, further causing stress, resulting changes potential, reduction copy number, PGC-1α TFAM proteins. addition respiratory chain genes proteins decreased. promoted activated downstream response, alleviated caused . ML385 an inhibitor, under protective are inhibited. When knocked down, mitochondria protects from -induced through KEAP1/Nrf2/NQO1/PGC-1α/TFAM pathway.

Language: Английский

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Icariside II Alleviates Chondrocyte Inflammatory Injury by Inhibiting the TNIP2/NF-κB Pathway

Cell Biochemistry and Biophysics, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 7, 2025

Language: Английский

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