China
Africa
Explore chapters and articles related to this topic
Introduction to Human Cytochrome P450 Superfamily
Published in Shufeng Zhou, Cytochrome P450 2D6, 2018
CYP27A1 (also called sterol 27-hydroxylase) is mainly expressed in the liver and located in mitochondria. CYP27A1 mRNA is also observed in macrophages (Gottfried et al. 2006), leukocytes (Shiga et al. 1999), skin fibroblasts (Garuti et al. 1997), kidney (Gascon-Barre et al. 2001), and the arterial wall (Shanahan et al. 2001). The enzyme catalyzes the 27-hydroxylation of cholesterol and 25-hydroxylation of vitamin D3 (Jones et al. 2014; Norlin and Wikvall 2007; Pikuleva 2006; Pikuleva et al. 1997; Tieu et al. 2012; Wikvall 2001). Bioactivation of cholesterol into bile acids is crucial for regulation of cholesterol homeostasis. The “classic” pathway of bile acid formation starts with a 7α-hydroxylation of cholesterol by CYP7A1 in the liver, while the “acidic” pathway starts with a hepatic or extrahepatic 27-hydroxylation by CYP27A1 (Norlin and Wikvall 2007). Formation of cholic acid requires insertion of a 12α-hydroxyl group catalyzed by CYP8B1. Oxysterols are precursors to bile acids, participate in cholesterol transport, and are known to affect the expression of several genes in cholesterol homeostasis. CYP27A1 is attached to the inner mitochondrial membrane and substrates appear to reach the active site through the membrane phase. The distance between the hydroxylation site and the end of the site chain is proportional to the regioselectivity of the enzyme (Dilworth et al. 1995).
The Role of Light and Electromagnetic Fields in Maintaining Vascular Health
Published in Aruna Bakhru, Nutrition and Integrative Medicine, 2018
Oxysterol sulfates are derivatives of cholesterol that have been oxidized by CYP enzymes and then sulfated by sulfotransferases (SULTs). They are produced in the liver, and it has recently become apparent that they are regulatory signaling molecules with dramatic responses when present at low concentrations [48]. In the liver, they have remarkably beneficial effects in suppressing the release of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and pro-inflammatory cytokines following exposure to lipopolysaccharides (LPS) and tumor necrosis factor α (TNFα). They reduce the build-up of lipid stores in the liver (fatty liver disease), protect from apoptosis, and promote proliferation of liver cells. They also promote bile flow, which is essential for the digestion of dietary fats, among many other roles. In many cases, the same oxysterols, when unsulfated, have the opposite effect.
Plasma levels of oxysterols 7-ketocholesterol and cholestane-3β, 5α, 6β-triol in patients with allergic asthma
Published in Journal of Asthma, 2023
Behnoush Nasr Zanjani, Afshin Samadi, Selen Yilmaz Isikhan, Incilay Lay, Sengul Beyaz, Asli Gelincik, Suna Buyukozturk, Nazli Arda
Oxysterols are defined as the final products of cholesterol oxidation. Generally, they are present in very low concentrations in mammalian tissues. These metabolites play key roles in health and disease, particularly in the development and regulation of immune cell responses (29). The roles of specific oxysterols as mediators, and their use as appropriate markers for diagnosing certain diseases, such as diabetes mellitus, Alzheimer’s disease, multiple sclerosis, osteoporosis, lung cancer, breast cancer, and infertility have been reported in various studies (30–33). Measuring 7-KC in combination with C-triol levels may be helpful in the prediction of oxidative stress in several diseases. For example, 7-KC and C-triol have been found to increase in diabetes mellitus (34) and neurodegenerative diseases (35). However, there has been no clinical study on oxysterols in allergic asthma to date, although it is known that they are directly related to oxidation, inflammation, and immunity (36).
The Controlling Nutritional Status (CONUT) Score and Prognosis in Malignant Tumors: A Systematic Review and Meta-Analysis
Published in Nutrition and Cancer, 2022
Junhao Chen, Pan Song, Zhufeng Peng, Zhenghuan Liu, Luchen Yang, Linchun Wang, Jing Zhou, Qiang Dong
Third, cholesterol plays a key role in maintaining cellular function. In addition to being an essential component of the plasma membrane, cholesterol also participates in intracellular signal transduction and the synthesis of steroid hormones (90). Furthermore, cholesterol metabolites have been demonstrated to be connected to cancer development (91). Oxysterol is an oxidation product of cholesterol, and many oxysterols, including 7α-hydroxycholesterol, 7β-hydroxycholesterol and 25- hydroxycholesterol, have been reported to inhibit proliferation in various cancer types (92). Studies have also reported that hypocholesterolemia is significantly associated with poor prognosis of various malignant tumors (93–95). Other immune-inflammatory indicators, such as PNI and mGPS, do not include cholesterol levels, which represent an important component of the CONUT score.
Rivaroxaban protects from the oxysterol-induced damage and inflammatory activation of the vascular endothelium
Published in Tissue Barriers, 2021
Paulina Gorzelak-Pabis, Marlena Broncel, Katarzyna Wojdan, Adrian Gajewski, Maciej Chalubinski, Mateusz Gawrysiak, Ewelina Wozniak
Oxysterols are bioactive lipids that act as regulators of inflammation and cell viability. Formation of oxysterols in atherotic lesions is confirmed. 25-hydroxycholesterol (25-OHC) is a type of oxidized cholesterol, which participates in chronic inflammation, vascular proliferation, and development of atherosclerosis.7 It is known that the control of coagulation environment is essential in the treatment of coronary artery disease. Mechanisms by which the inhibition of FXa interrupts atherosclerotic plaque development are complex.8 Histological analyses demonstrated that rivaroxaban significantly decreased lipid deposition, collagen loss, macrophage accumulation, and matrix metallopeptidase-9 (MMP-9) expression in atherosclerotic plaques in the aortic root of ApoE(-/-) mice. Moreover, rivaroxaban significantly reduced mRNA expression of inflammatory molecules, such as MMP-9 and TNF-α.9 In our previous study on HUVECs, we showed that rivaroxaban was able to reduce the level of oxidative damage induced by 25-OHC.10