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Clinical Effects of Pollution
Published in William J. Rea, Kalpana D. Patel, Reversibility of Chronic Disease and Hypersensitivity, Volume 5, 2017
William J. Rea, Kalpana D. Patel
While it is clear that CYP enzymes play an important role in bile acid synthesis and in cholesterol homeostasis, the details have not yet been worked out.979 However, some mouse knockout experiments produce embryonically lethal effects, pointing to the importance of these enzymes to biological systems. Disruption of CYP7A1, involved in bile acid synthesis in mice, induces elevated serum cholesterol and early death. Frequently, the food and chemically sensitive patient has increased cholesterol probably through this mechanism.
Regulation of cytochrome P450 expression by microRNAs and long noncoding RNAs: Epigenetic mechanisms in environmental toxicology and carcinogenesis
Published in Journal of Environmental Science and Health, Part C, 2019
Dongying Li, William H. Tolleson, Dianke Yu, Si Chen, Lei Guo, Wenming Xiao, Weida Tong, Baitang Ning
lncRNAs also modulate CYP expression at the post-transcriptional level. A high level of cholesterol in rats activates the C-EBPβ pathway, which promotes the expression of lnc-HC, a recently-identified hepatocyte-specific lncRNA. Lnc-HC interacting with hnRNPA2B1 increases the nuclear localization of hnRNPA2B1. This RNA/protein complex binds to CYP7A1 (cholesterol 7a-hydroxylase) mRNA and decreases its stability, resulting in decreased CYP7A1 protein levels.48 As CYP7A1 has a critical role in converting cholesterol to bile acids, the reduction in CYP7A1 expression leads to cholesterol accumulation. This lncRNA/heterogenous nuclear ribonucleoprotein interaction is essential for CYP7A1 mRNA binding and degradation, even though lncRNAs can hybridize with mRNA directly, highlighting the post-transcriptional control that lncRNAs exert in metabolic systems.