The role of oxysterols in human body and disease
1. Introduction
Oxysterols are 27-carbon derivatives of cholesterol created by spontaneous or enzymatic oxidation (Figure 1, (Brown and Jessup, 2009)). The oxidation of cholesterol occurs either on the side chain or on the sterol core. Side chain oxidation generates, e.g., 24-hydroxycholesterol (24-HC), 25-hydroxycholesterol (25-HC) or 27-hydroxycholesterol (27-HC) while the core oxidation gives rise to ring oxysterols, mostly ring-B oxysterols, such as 6-hydroxycholesterol (6-HC), 7-hydroxycholesterol (7-HC) and 7-ketocholesterol (7-KC).
In very low concentrations, oxysterols present natural components of the human body and mediate many physiological functions. Oxysterols influence several signaling …show more content…
They arise as a result of cholesterol oxidation in animal products, such as eggs, red meat, liver, or dairy products (Guardiola et al., 2002). The oxysterol content in these products is influenced by ambient conditions (Zanardi et al., 2002; Soupas et al., 2004), e.g., temperature, light, or presence of oxygen in the place, where the food is stored. The saturation of lipid content in cell membrane also influences the sterol oxidation extent (Soupas et al., 2004). Oxysterols enter the human body also through the skin. Tonello and Polli showed, that non-enzymatic oxidation of certain cosmetic products containing phytosterols is another way how oxysterols enter the organism (Tonello and Poli, …show more content…
For example, OSBP1 protein regulates transport of sphingomyelin and ceramide molecules (Perry and Ridgway, 2006). Moreover, it can also influence sterol metabolism via negative regulation of ABCA1 transporter through regulation of its gene expression and protein destabilization (Bowden and Ridgway, 2008). The regulation of ABCA1 is also mediated by ORP8 (Yan et al., 2008). Overexpression or knock-out experiments with ORP2 (OMIM: 606731) (Hynynen et al., 2005), ORP5 (OMIM: 606733) (Du et al., 2011), and ORP8 (OMIM: 606736) (Zhou et al., 2011) caused alteration in cholesterol level, suggesting that these ORPs also take part in cholesterol metabolism or trafficking. The modulation of cholesterol metabolism may be mediated through transcription factors. Accordingly, ORP8 was shown to regulate activity of SREBP, presumably by an indirect mechanism (Zhou et al., 2011). ORP2 binds LXRs and is required for expression of LXR target genes (Escajadillo et al., 2016).
OSBP family modulates also vesicular transport. OSBP1 interacts with VAP-A protein, which is important for protein and lipid transport to the Golgi apparatus (Wyles et al., 2002). The depletion of OSBP1 causes changes in localization of intra-Golgi v-SNARE proteins (Nishimura et al.,
1. Introduction
Oxysterols are 27-carbon derivatives of cholesterol created by spontaneous or enzymatic oxidation (Figure 1, (Brown and Jessup, 2009)). The oxidation of cholesterol occurs either on the side chain or on the sterol core. Side chain oxidation generates, e.g., 24-hydroxycholesterol (24-HC), 25-hydroxycholesterol (25-HC) or 27-hydroxycholesterol (27-HC) while the core oxidation gives rise to ring oxysterols, mostly ring-B oxysterols, such as 6-hydroxycholesterol (6-HC), 7-hydroxycholesterol (7-HC) and 7-ketocholesterol (7-KC).
In very low concentrations, oxysterols present natural components of the human body and mediate many physiological functions. Oxysterols influence several signaling …show more content…
They arise as a result of cholesterol oxidation in animal products, such as eggs, red meat, liver, or dairy products (Guardiola et al., 2002). The oxysterol content in these products is influenced by ambient conditions (Zanardi et al., 2002; Soupas et al., 2004), e.g., temperature, light, or presence of oxygen in the place, where the food is stored. The saturation of lipid content in cell membrane also influences the sterol oxidation extent (Soupas et al., 2004). Oxysterols enter the human body also through the skin. Tonello and Polli showed, that non-enzymatic oxidation of certain cosmetic products containing phytosterols is another way how oxysterols enter the organism (Tonello and Poli, …show more content…
For example, OSBP1 protein regulates transport of sphingomyelin and ceramide molecules (Perry and Ridgway, 2006). Moreover, it can also influence sterol metabolism via negative regulation of ABCA1 transporter through regulation of its gene expression and protein destabilization (Bowden and Ridgway, 2008). The regulation of ABCA1 is also mediated by ORP8 (Yan et al., 2008). Overexpression or knock-out experiments with ORP2 (OMIM: 606731) (Hynynen et al., 2005), ORP5 (OMIM: 606733) (Du et al., 2011), and ORP8 (OMIM: 606736) (Zhou et al., 2011) caused alteration in cholesterol level, suggesting that these ORPs also take part in cholesterol metabolism or trafficking. The modulation of cholesterol metabolism may be mediated through transcription factors. Accordingly, ORP8 was shown to regulate activity of SREBP, presumably by an indirect mechanism (Zhou et al., 2011). ORP2 binds LXRs and is required for expression of LXR target genes (Escajadillo et al., 2016).
OSBP family modulates also vesicular transport. OSBP1 interacts with VAP-A protein, which is important for protein and lipid transport to the Golgi apparatus (Wyles et al., 2002). The depletion of OSBP1 causes changes in localization of intra-Golgi v-SNARE proteins (Nishimura et al.,