The abilities of 22,23-epoxy-2-aza-2,3-dihydrosqualene and the corresponding N-oxide, 22,23-epoxy-2-aza-2,3-dihydrosqualene-N-oxide, to inhibit sterol biosynthesis were studied in microsomes and cells of Saccharomyces cerevisiae and Candida albicans. 22,23-Epoxy-2-aza-2,3-dihydrosqualene, which differs from the other inhibitor only in lacking oxygen at position 2, exhibited higher inhibitory properties in all preparations tested. The different levels of effectiveness of the two azasqualene derivatives were evident mostly in microsomes from S. cerevisiae (the 50 inhibitory concentrations of the 2-aza derivative and the corresponding N-oxide on oxidosqualene cyclase were 30 and 120 microM respectively) and in cell cultures of the same strain (1 order of magnitude separated the inhibitory activities of the two compounds on sterol biosynthesis). A possible explanation for the differences between 22,23-epoxy-2-aza-2,3-dihydrosqualene and the corresponding N-oxide arose from the study of their metabolic fates in vivo and in vitro. While the 2-aza derivative did not undergo any transformation, the N-oxide compound was actively reduced to the corresponding amine in microsomes and in cells of both yeast strains. 22,23-Epoxy-2-aza-2,3-dihydrosqualene-N-oxide seems to behave as a proinhibitor of sterol biosynthesis, becoming active only after transformation into the active form 22,23-epoxy-2-aza-2,3-dihydrosqualene.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC284660 | PMC |
| http://dx.doi.org/10.1128/AAC.38.9.1904 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Phytic acid-based nanomedicine against mTOR represses lipogenesis and immune response for metabolic dysfunction-associated steatohepatitis therapy.
Life Metab
December 2024
State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and Xijing Hospital of Digestive Diseases, Air Force Medical University, Xi'an, Shaanxi 710032, China.
Metabolic dysfunction-associated steatohepatitis (MASH) is one of the most common chronic liver diseases and is mainly caused by metabolic disorders and systemic inflammatory responses. Recent studies have indicated that the activation of the mammalian (or mechanistic) target of rapamycin (mTOR) signaling participates in MASH progression by facilitating lipogenesis and regulating the immune microenvironment. Although several molecular medicines have been demonstrated to inhibit the phosphorylation or activation of mTOR, their poor specificity and side effects limit their clinical application in MASH treatment.
View Article and Find Full Text PDFCholesterol metabolism regulator SREBP2 inhibits HBV replication via suppression of HBx nuclear translocation.
Front Immunol
January 2025
Department of Hepatology, Center for Pathogen Biology and Infectious Diseases, Institute of Translational Medicine, The First Hospital of Jilin University, Changchun, Jilin, China.
The intricate link between cholesterol metabolism and host immune responses is well recognized, but the specific mechanisms by which cholesterol biosynthesis influences hepatitis B virus (HBV) replication remain unclear. In this study, we show that SREBP2, a key regulator of cholesterol metabolism, inhibits HBV replication by interacting directly with the HBx protein, thereby preventing its nuclear translocation. We also found that inhibiting the ER-to-Golgi transport of the SCAP-SREBP2 complex or blocking SREBP2 maturation significantly enhances HBV suppression.
View Article and Find Full Text PDFAssociations of the triglyceride-glucose index and remnant cholesterol levels with the prevalence of Carotid Plaque in patients with type 2 diabetes: a retrospective study.
Lipids Health Dis
January 2025
Department of Endocrinology, The Second Affiliated Hospital of Anhui Medical University, Hefei Anhui, 230601, China.
Background: The triglyceride-glucose (TyG) index has been identified as an alternative biomarker for insulin resistance (IR), while residual cholesterol (RC) is a simple, cost-effective, and easily detectable lipid metabolite. However, the associations of these two markers with carotid plaque presence remain unclear. Thus, this study aimed to explore their associations with carotid plaque presence.
View Article and Find Full Text PDFChronic stress-induced cholesterol metabolism abnormalities promote ESCC tumorigenesis and predict neoadjuvant therapy response.
Proc Natl Acad Sci U S A
February 2025
Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450000, China.
Recent studies have demonstrated that chronic stress can enhance the development of multiple human diseases, including cancer. However, the role of chronic stress in esophageal carcinogenesis and its underlying molecular mechanisms remain unclear. This study uncovered that dysregulated cholesterol metabolism significantly promotes esophageal carcinogenesis under chronic stress conditions.
View Article and Find Full Text PDFMassive endocytosis mechanisms are involved in uptake of HIV-1 particles by monocyte-derived dendritic cells.
Front Immunol
January 2025
IrsiCaixa, Badalona, Spain.
Introduction: HIV-1 exploits dendritic cells (DCs) to spread throughout the body via specific recognition of gangliosides present on the viral envelope by the CD169/Siglec-1 membrane receptor. This interaction triggers the internalization of HIV-1 within a structure known as the sac-like compartment. While the mechanism underlying sac-like compartment formation remains elusive, prior research indicates that the process is clathrin-independent and cell membrane cholesterol-dependent and involves transient disruption of cortical actin.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!