Pathophysiological role of 27-hydroxycholesterol in human diseases

Kim, Dayea; Lee, Kwang Min; Lee, Chanhee; Jo, Yeon Suk; Muradillaevna, Muradillaeva Shakhnoza; Kim, Jae Ho; Yoon, Jong Hyuk; Song, Parkyong

doi:10.1016/j.jbior.2021.100837

Cited by 9 publications

(9 citation statements)

References 54 publications

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“…In contrast to 24-hydroxycholesetrol, which is considered a protective factor to Alzheimer's disease, 27-hydroxycholesterol is considered to be a risk factor and is increased in the cerebrospinal fluid and blood plasma of early-onset Alzheimer's disease [123]. The release of 27-hydroxycholesterol from circulation into the brain reduces the brain glucose uptake level, Glut4 expression, and spatial memory, and can activate the renin-angiotensin system (RAS), leading to oxidative stress, impaired cognitive function, and ischemic brain injury.…”

Section: Alzheimer's Diseasementioning

confidence: 99%

“…The release of 27-hydroxycholesterol from circulation into the brain reduces the brain glucose uptake level, Glut4 expression, and spatial memory, and can activate the renin-angiotensin system (RAS), leading to oxidative stress, impaired cognitive function, and ischemic brain injury. In addition, the RAS activation may also contribute to hypertension and insulin resistance, risk factors for Alzheimer's disease [123].…”

Section: Alzheimer's Diseasementioning

confidence: 99%

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Effects of Oxysterols on Immune Cells and Related Diseases

Freitas

Levy

Reichert

et al. 2022

Cells

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Oxysterols are the products of cholesterol oxidation. They have a wide range of effects on several cells, organs, and systems in the body. Oxysterols also have an influence on the physiology of the immune system, from immune cell maturation and migration to innate and humoral immune responses. In this regard, oxysterols have been involved in several diseases that have an immune component, from autoimmune and neurodegenerative diseases to inflammatory diseases, atherosclerosis, and cancer. Here, we review data on the participation of oxysterols, mainly 25-hydroxycholesterol and 7α,25-dihydroxycholesterol, in the immune system and related diseases. The effects of these oxysterols and main oxysterol receptors, LXR and EBI2, in cells of the immune system (B cells, T cells, macrophages, dendritic cells, oligodendrocytes, and astrocytes), and in immune-related diseases, such as neurodegenerative diseases, intestinal diseases, cancer, respiratory diseases, and atherosclerosis, are discussed.

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Section: Alzheimer's Diseasementioning

confidence: 99%

Section: Alzheimer's Diseasementioning

confidence: 99%

Effects of Oxysterols on Immune Cells and Related Diseases

Freitas

Levy

Reichert

et al. 2022

Cells

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“…Oxysterols are de novo synthesized from cholesterol by enzyme belonging to the cytochrome P450 family [ 31 , 32 ]. The major oxysterol synthesized in the liver and other organs is 27-hydroxycholesterol (27-HC) ( Figure 3 ), which has a positive correlation with plasma cholesterol levels [ 33 ]. 24(S)-hydroxycholesterol (24S-HC) is highly synthesized in the brain.…”

Section: Intake and De Novo Synthesis Of Cholesterol And Oxysterolsmentioning

confidence: 99%

“…25-HC promotes activity of acyl-CoA cholesterol acyltransferase (ACAT) to the esterification of cholesterol and represses nSREBP2-induced genes, that regulate cholesterol availability in the cells [ 46 ]. 27-HC, an endogenous oxysterol produced from cholesterol by cholesterol 27-hydroxylase (CYP27A1), also regulates intracellular cholesterol homeostasis [ 32 , 33 ]. However, among oxysterols, the synthesis of 25-HC is highly promoted in macrophages and dendritic cells (DCs) in pathogen infection and is engaged in multiple processes in intrinsic immunity (see Section 3.6 ) [ 45 , 46 ].…”

Section: Intake and De Novo Synthesis Of Cholesterol And Oxysterolsmentioning

confidence: 99%

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The Impacts of Cholesterol, Oxysterols, and Cholesterol Lowering Dietary Compounds on the Immune System

Yanagisawa

Asai

et al. 2022

IJMS

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Cholesterol and its oxidized forms, oxysterols, are ingested from foods and are synthesized de novo. Cholesterol and oxysterols influence molecular and cellular events and subsequent biological responses of immune cells. The amount of dietary cholesterol influence on the levels of LDL cholesterol and blood oxysterols plays a significant role in the induction of pro-inflammatory state in immune cells, leading to inflammatory disorders, including cardiovascular disease. Cholesterol and oxysterols synthesized de novo in immune cells and stroma cells are involved in immune homeostasis, which may also be influenced by an excess intake of dietary cholesterol. Dietary compounds such as β-glucan, plant sterols/stanols, omega-3 lipids, polyphenols, and soy proteins, could lower blood cholesterol levels by interfering with cholesterol absorption and metabolism. Such dietary compounds also have potential to exert immune modulation through diverse mechanisms. This review addresses current knowledge about the impact of dietary-derived and de novo synthesized cholesterol and oxysterols on the immune system. Possible immunomodulatory mechanisms elicited by cholesterol-lowering dietary compounds are also discussed.

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Urolithin A: A promising selective estrogen receptor modulator and 27‐hydroxycholesterol attenuator in breast cancer

Vini

Jaikumar

Remadevi

et al. 2023

Phytotherapy Research

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Abstract27‐hydroxycholesterol (27‐HC) is an oxysterol that acts as an endogenous selective estrogen receptor modulator (SERM), and its adverse effects on breast cancer via the estrogen receptor (ER) have provided new insights into the pathology of cholesterol–linked breast cancer. Our earlier in vitro experiments showed that the methanolic extract of pomegranate could exhibit SERM properties and compete with 27‐HC. The major constituents of pomegranate are ellagitannins and ellagic acid, which are converted into urolithins by the colonic microbiota. In recent years, urolithins, especially urolithin A (UA) and urolithin B (UB), have been reported to have a plethora of advantageous effects, including antiproliferative and estrogenic activities. In this study, we attempted to determine the potential of urolithins in antagonizing and counteracting the adverse effects of 27‐HC in breast cancer cells. Our findings suggested that UA had an antiproliferative capacity and attenuated the proliferative effects of 27‐HC, resulting in subsequent loss of membrane potential and apoptosis in breast cancer cells. Further, UA induced estrogen response element (ERE) transcriptional activity and modulated estrogen‐responsive genes, exhibiting a SERM‐like response concerning receptor binding. Our in vivo hollow fiber assay results showed a loss of cell viability in breast cancer cells upon UA consumption, as well as a reduction in 27‐HC‐induced proliferative activity. Additionally, it was shown that UA did not induce uterine proliferation or alter blood biochemical parameters. Based on these findings, we can conclude that UA has the potential to act as a potent estrogen receptor alpha (ERα) modulator and 27‐HC antagonist. UA is safe to consume and is very well tolerated. This study further opens up the potential of UA as ER modulator and its benefits in estrogen‐dependent tissues.

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Pathophysiological role of 27-hydroxycholesterol in human diseases

Cited by 9 publications

References 54 publications

Effects of Oxysterols on Immune Cells and Related Diseases

Effects of Oxysterols on Immune Cells and Related Diseases

The Impacts of Cholesterol, Oxysterols, and Cholesterol Lowering Dietary Compounds on the Immune System

Urolithin A: A promising selective estrogen receptor modulator and 27‐hydroxycholesterol attenuator in breast cancer

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