Heme oxygenase 1 (HO-1) is the first and rate-controlling enzyme in heme degradation. Bach1 is a mammalian transcriptional repressor of HO-1. To understand how zinc mesoporphyrin (ZnMP) induces the expression of HO-1, we investigated the effects of ZnMP on Bach1 mRNA and protein levels in human hepatoma Huh-7 cells by quantitative RT-PCR and Western blots. We found that ZnMP markedly up-regulated HO-1 mRNA and protein levels, and rapidly and significantly decreased Bach1 protein levels by increasing degradation of Bach1 protein [half life (t(1/2)) from 19 h to 45 min], whereas ZnMP did not influence Bach1 mRNA levels. The proteasome inhibitors, epoxomicin and MG132, significantly inhibited degradation of Bach1 by ZnMP in a dose-dependent fashion, indicating that the degradation of Bach1 by ZnMP is proteasome-dependent. Purified Bach1 C-terminal fragment bound heme, but there was no evidence for binding of ZnMP to the heme-binding region of Bach1. In conclusion, ZnMP produces profound post-transcriptional down-regulation of Bach1 protein levels and transcriptional up-regulation of HO-1. Our results indicate that ZnMP up-regulates HO-1 gene expression by markedly increasing Bach1 protein degradation in a proteasome-dependent manner.
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http://dx.doi.org/10.1016/j.bbagrm.2008.01.006 | DOI Listing |
Front Vet Sci
January 2025
College of Animal Science and Technology, Yangtze University, Jingzhou, China.
Among the various sources of selenium supplementations, the Se-methylselenocysteine (SeMC) is a natural organic selenium compound that has been demonstrated to have multiple advantages in terms of metabolism efficiency and biosafety in animals. Nevertheless, the genome-wide impact of SeMC on gene transcription remains to be elucidated. In this study, we employed an LPS-stimulated chicken HD11 macrophage-like cell model to identify the principal transcription factors involved in transcriptome regulation responsible for SeMC treatment.
View Article and Find Full Text PDFFree Radic Biol Med
January 2025
Department of Analytical Chemistry, Medical University of Białystok, Mickiewicza 2D, 15-222, Białystok, Poland. Electronic address:
The lack of effective protection against UVB radiation, that severely disrupts the metabolism of keratinocytes, underlines the search for bioactive compounds that would provide effective protection without causing side effects. Therefore, the aim of the study has been to assess the effect of two compounds, that are different in terms of structure and properties: 3-O-ethyl ascorbic acid-EAA (a stable derivative of vitamin C) and cannabigerol-CBG, used separately or concurrently, on the metabolism of keratinocytes previously exposed to UVB. The obtained results indicate diverse, yet mutually reinforcing localization of the tested compounds, both within the membrane structures and cytosol.
View Article and Find Full Text PDFNat Commun
January 2025
Center for Research Informatics, The University of Chicago, Chicago, IL, USA.
The fallopian tube undergoes extensive molecular changes during the menstrual cycle and menopause. We use single-cell RNA and ATAC sequencing to construct a comprehensive cell atlas of healthy human fallopian tubes during the menstrual cycle and menopause. Our scRNA-seq comparison of 85,107 pre- and 46,111 post-menopausal fallopian tube cells reveals substantial shifts in cell type frequencies, gene expression, transcription factor activity, and cell-to-cell communications during menopause and menstrual cycle.
View Article and Find Full Text PDFJ Appl Microbiol
January 2025
G.B. Elyakov Pacific Institute of Bioorganic Chemistry FEB RAS, 159 Prospect 100-letiya Vladivostoka, Vladivostok 690022, Russia.
Aims: The aim of this study was to evaluate the antioxidant and anti-inflammatory effects of marine fungal cerebroside flavuside B (FlaB) on Staphylococcus aureus-infected keratinocytes in in vitro skin wounds and to identify FlaB targets in bacterial and human cells.
Methods And Results: A combination of enzyme-linked immunosorbent assay (ELISA), plate spectrofluorimetry, and flow cytometry with fluorescence dye staining, scratch assay, and real-time cell imaging techniques was used to investigate the effects of FlaB on S. aureus-infected HaCaT keratinocytes.
J Am Chem Soc
January 2025
Department of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States.
Lipid nanoparticles (LNPs) have emerged as pivotal vehicles for messenger RNA (mRNA) delivery to hepatocytes upon systemic administration and to antigen-presenting cells following intramuscular injection. However, achieving systemic mRNA delivery to non-hepatocytes remains challenging without the incorporation of targeting ligands such as antibodies, peptides, or small molecules. Inspired by comb-like polymeric architecture, here we utilized a multiarm-assisted design to construct a library of 270 dendron-like degradable ionizable lipids by altering the structures of amine heads and multiarmed tails for optimal mRNA delivery.
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