A Facile LC-MS Method for Profiling Cholesterol and Cholesteryl Esters in Mammalian Cells and Tissues DOI

Aakash Chandramouli,

Siddhesh S. Kamat

Biochemistry, Journal Year: 2024, Volume and Issue: 63(18), P. 2300 - 2309

Published: July 10, 2024

Cholesterol is central to mammalian lipid metabolism and serves many critical functions in the regulation of diverse physiological processes. Dysregulation cholesterol causally linked numerous human diseases, therefore, vivo, concentrations flux cholesteryl esters (fatty acid cholesterol) are tightly regulated. While mass spectrometry has been an analytical method choice for detecting biological samples, hydrophobicity, chemically inert nature, poor ionization these neutral lipids have often proved a challenge developing lipidomics compatible liquid chromatography-mass (LC-MS) methods study them. To overcome this problem, here, we report reverse-phase LC-MS that with existing high-throughput strategies capable identifying quantifying from cells tissues. Using sensitive yet robust method, profiled different cell lines tissues provide comprehensive picture content Specifically, among esters, find largely possess monounsaturated polyunsaturated variants. Taken together, our class opens new avenues understanding systemic tissue-level under various conditions.

Language: Английский

Neuroinflammation in Alzheimer disease DOI
Wiesje M. van der Flier, Wiesje M. van der Flier,

Frank Jessen

et al.

Nature reviews. Immunology, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 9, 2024

Language: Английский

Citations

28
Silencing of the plant‐derived horizontally transferred gene BtSC5DL effectively controls Bemisia tabaci MED DOI Open Access
Yifan Liu, Gong Cheng, Yuan Hu

et al.

Pest Management Science, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 11, 2025

Abstract BACKGROUND The whitefly Bemisia tabaci is a notorious agricultural pest known for its ability to cause significant crop damage through direct feeding and virus transmission. Its remarkable adaptability reproductive capacity are linked acquire integrate horizontally transferred genes (HTGs) into genome. These HTGs increase the physiological metabolic capacities of this pest, including cholesterol synthesis, which critical survival success. Among these genes, we identified plant‐derived B. Δ7‐sterol C5‐desaturase‐like gene ( BtSC5DL ), plays pivotal role in metabolism biology. RESULTS In study, cloned from Mediterranean (MED). Bioinformatics molecular analyses revealed that was plants millions years ago now stably expressed species. Silencing dsRNA resulted reductions egg production content MED. Furthermore, virus‐induced silencing (VIGS) experiments confirmed long‐term suppression had notable control populations. CONCLUSION Our results demonstrate crucial biosynthesis MED suggest acquisition significantly enhances findings provide theoretical basis development RNA interference (RNAi)‐based strategies targeting , offering potential new approach effective management populations settings. © 2025 Society Chemical Industry.

Language: Английский

Citations

2
Sterol imbalances and cholesterol‐24‐hydroxylase dysregulation is linked to the underlying progression of multiple sclerosis DOI Creative Commons
Lauren Griffiths, Kristen Hawkins, Eylan Yutuc

et al.

Brain Pathology, Journal Year: 2025, Volume and Issue: unknown

Published: March 5, 2025

Disability worsening in multiple sclerosis (MS) is linked to neurodegeneration. Cholesterol homeostasis essential for normal brain function. CYP46A1, crucial cholesterol turnover and reduced some neurodegenerative diseases, a potential neuroprotective target. We hypothesized that CYP46A1 downregulated MS brains dysbalance. Mass spectrometric analysis of sterols was performed from matched plasma cerebrospinal fluid (CSF) an all-female cohort (n = 32, mean age 33). status recorded at baseline follow-up. tissue samples 11; 7 females; ages 38-67; 10 Secondary Progressive MS, 1 Primary MS; Disease Duration: 13-49 years) control 8; 3 41-68) analysed pathological regions using mass spectrometry RNA expression in-situ hybridization. Significant dysregulation 25-hydroxycholesterol, 27-hydroxycholesterol 3β-hydroxycholestenoic acid CSF correlated with disability follow-up the patient population. In tissue, cholesterol, 24S-hydroxycholesterol 24S,25-epoxycholesterol were observed white matter lesions (p < 0.05), activity. enriched neurons, reductions grey non-lesions compared controls 0.01). metabolism dysregulated associated neuron-specific expression. Modulating druggable target, may benefit progressive MS.

Language: Английский

Citations

1
The translational potential of cholesterol-based therapies for neurological disease DOI
Marta Valenza, Giulia Birolini, Elena Cattaneo

et al.

Nature Reviews Neurology, Journal Year: 2023, Volume and Issue: 19(10), P. 583 - 598

Published: Aug. 29, 2023

Language: Английский

Citations

19
Chemical Inhibition of Sterol Biosynthesis DOI Creative Commons
Eric S. Peeples, Károly Mirnics, Željka Korade

et al.

Biomolecules, Journal Year: 2024, Volume and Issue: 14(4), P. 410 - 410

Published: March 28, 2024

Cholesterol is an essential molecule of life, and its synthesis can be inhibited by both genetic nongenetic mechanisms. Hundreds chemicals that we are exposed to in our daily lives alter sterol biosynthesis. These also encompass various classes FDA-approved medications, including (but not limited to) commonly used antipsychotic, antidepressant, antifungal, cardiovascular medications. medications interfere with enzymes the post-lanosterol biosynthetic pathway, giving rise complex biochemical changes throughout body. The consequences these short- long-term homeostatic disruptions mostly unknown. We performed a comprehensive review literature built catalogue chemical agents capable inhibiting This process identified significant gaps existing knowledge, which fall into two main areas: mechanisms biosynthesis altered arise from inhibitions different steps pathway. outcome reinforced inhibition often-overlooked mechanism result adverse there need develop new safety guidelines for use (novel already approved) side effects, especially during pregnancy.

Language: Английский

Citations

7
Exploring the Dynamic Changes of Brain Lipids, Lipid Rafts, and Lipid Droplets in Aging and Alzheimer’s Disease DOI Creative Commons
Michele Cerasuolo, Irene Di Meo, Maria Chiara Auriemma

et al.

Biomolecules, Journal Year: 2024, Volume and Issue: 14(11), P. 1362 - 1362

Published: Oct. 26, 2024

Aging induces complex changes in the lipid profiles across different areas of brain. These can affect function brain cells and may contribute to neurodegenerative diseases such as Alzheimer's disease. Research shows that while overall profile human remains quite steady throughout adulthood, specific occur with age, especially after age 50. include a slow decline total content shifts composition fatty acids, particularly glycerophospholipids cholesterol levels, which vary depending on region. Lipid rafts play crucial role maintaining membrane integrity facilitating cellular signaling. In context disease, have been associated development For example, alterations raft lead increased accumulation amyloid β (Aβ) peptides, contributing neurotoxic effects. droplets store neutral lipids are key for energy metabolism. As organisms dynamics change, evidence suggesting metabolic activity over time. This reduced an imbalance synthesis mobilization, processes. model like Drosophila, studies shown metabolism be influenced by diet insulin signaling pathways, balance. The interplay between metabolism, oxidative stress, inflammation is critical aging peroxidation, consequence formation reactive aldehydes further damage neurons. Inflammatory processes also disrupt pathology AD. Consequently, oxidized integrity, influencing pathways involved neuronal survival function.

Language: Английский

Citations

7
Cholesterol-dependent amyloid β production: space for multifarious interactions between amyloid precursor protein, secretases, and cholesterol DOI Creative Commons
Vladimı́r Rudajev, Jiřı́ Novotný

Cell & Bioscience, Journal Year: 2023, Volume and Issue: 13(1)

Published: Sept. 13, 2023

Abstract Amyloid β is considered a key player in the development and progression of Alzheimer’s disease (AD). Many studies investigating effect statins on lowering cholesterol suggest that there may be link between levels AD pathology. Since one most abundant lipid molecules, especially brain tissue, it affects membrane-related processes, including formation dangerous form amyloid β, Aβ42. The entire Aβ production system, which includes precursor protein (APP), β-secretase, complex γ-secretase, highly dependent membrane content. Moreover, can affect amyloidogenesis many ways. Cholesterol influences stability activity secretases, but also dictates their partitioning into specific cellular compartments cholesterol-enriched rafts, where amyloidogenic machinery predominantly localized. complicated relationships have been found interaction APP, not only APP localization precise character dimerization processing by important for different lengths . In this review, we describe intricate web interdependence levels, distribution, cholesterol-dependent Aβ, major AD.

Language: Английский

Citations

15
Cholesterol and oxysterols in retinal neuron-glia interactions: relevance for glaucoma DOI Creative Commons

Elodie Masson,

Jeanne Serrano,

Elise Léger-Charnay

et al.

Frontiers in Ophthalmology, Journal Year: 2024, Volume and Issue: 3

Published: Jan. 3, 2024

Cholesterol is an essential component of cellular membranes, crucial for maintaining their structural and functional integrity. It especially important nervous tissues, including the retina, which rely on high amounts plasma membranes transmission signal. While cholesterol by far most abundant sterol, retina also contains precursors metabolites, oxysterols, are bioactive molecules. lack or excess deleterious some oxysterols known effect neuron survival. homeostasis must therefore be maintained. Retinal glial cells, Müller principal cells vertebrate provide mechanical, nutritional, metabolic support neighboring neurons. Several pieces evidence indicate that major actors in as it other brain. This process based a close cooperation with neurons, sterols can signaling molecules participating glia-neuron interactions. implication age-related macular degeneration now recognized, epidemiological laboratory data, its role glaucoma still scarce. The association between cholesterolemia controversial, but experimental data suggest could take part pathological processes. has been demonstrated implicated development through ambivalent reactive retinal gliosis process. early steps contribute to favor survival ganglion targeted during glaucoma. If persists, dysregulation neuroprotective functions, cytotoxic effects gliotic disruption interactions lead acceleration cell death. Sterols play response glaucomatous injury. represents understudied attractive topic better understand conceive novel preventive curative strategies. present review describes current knowledge i) sterol metabolism ii) potential glaucoma, iii) possible relationships Focus put

Language: Английский

Citations

5
Aging, sex, metabolic and life experience factors: Contributions to neuro-inflammaging in Alzheimer’s disease research DOI Creative Commons

Pasindu Hansana Singhaarachchi,

Péter Antal, Frédéric Calon

et al.

Neuroscience & Biobehavioral Reviews, Journal Year: 2024, Volume and Issue: 162, P. 105724 - 105724

Published: May 16, 2024

Alzheimer's disease (AD) is prevalent around the world, yet our understanding of still very limited. Recent work suggests that cornerstone AD may include inflammation accompanies it. Failure a normal pro-inflammatory immune response to resolve lead persistent central contributes unsuccessful clearance amyloid-beta plaques as they form, neuronal death, and ultimately cognitive decline. Individual metabolic, dietary (lipid) profiles can differentially regulate this inflammatory process with aging, obesity, poor diet, early life stress other factors contributing greater risk developing AD. Here, we integrate evidence for interface between these factors, how contribute brain milieu. In particular, discuss importance appropriate polyunsaturated fatty acids (PUFA) in diet metabolism specialised pro-resolving mediators (SPMs); raising possibility strategies improve outlook.

Language: Английский

Citations

5
Microbial metabolites as modulators of host physiology DOI
Susan A. Joyce, David J. Clarke

Advances in microbial physiology/Advances in Microbial Physiology, Journal Year: 2024, Volume and Issue: unknown, P. 83 - 133

Published: Jan. 1, 2024

Language: Английский

Citations

4