Raghavamenon Achuthan C., Gao Xueli, Atkins-Ball Deidra S., Varikuti Sanjay, Parinandi Narasimham L., Uppu Rao M.
Department of Environmental Toxicology and the Health Research Center, Southern University and A&M College, Baton Rouge, LA, USA
Present address: Department of Biochemistry, Amala Cancer Research Center, Thrissur, Kerala, India
Cholesterol is an important plasma membrane component, precursor for hormones and vitamins, and is a regulator of metabolism. However, the oxidized forms of cholesterol (oxysterols) can cause toxicity and induce pro-inflammatory responses and are implicated in chronic degenerative diseases. In general, oxysterols with a modified sidechain serve in various physiological and/or pathophysiological functions. The source of these oxysterols may be exogenous, from the food we ingest, or endogenous, as the by-product of normal cholesterol metabolism, free radical-mediated oxidation, or autoxidation of cholesterol. This chapter discusses the nature of oxysterols as oxidized cholesterol species, oxysterol signaling and pathophysiology, oxysterols and neurodegenerative diseases, ozone-oxidized cholesterol as a new class of oxysterols, detection of 3β-hydroxy-5-oxo-5,6-secocholestan-6-al (cholesterol secoaldehyde, ChSeco or atheronal-A) at sites of inflammation and evidence for in vivo existence, cytotoxicity of ChSeco and pro-inflammatory actions in the cells of mammalian systems, and ChSeco signaling in neuronal cells and implications in Alzheimer’s pathology.
胆固醇是一种重要的质膜成分、激素和维生素的前体，也是新陈代谢的调节剂。然而，胆固醇的氧化形式（氧化甾醇）会导致毒性并引发促炎反应，还与慢性退行性疾病有关。一般来说，具有修饰侧链的氧化甾醇具有多种生理和/或病理生理功能。这些氧化甾醇的来源可能是外源性的，来自我们摄入的食物，也可能是内源性的，作为正常胆固醇代谢、自由基介导的氧化或胆固醇自氧化的副产物。本章讨论了氧化甾醇作为氧化胆固醇种类的性质、氧化甾醇信号传导和病理生理学、氧化甾醇与神经退行性疾病、作为一类新型氧化甾醇的臭氧氧化胆固醇、炎症部位3β-羟基-5-氧代-5,6-断胆甾烷-6-醛（胆固醇断醛，ChSeco或动脉粥样硬化醛-A）的检测及体内存在证据、ChSeco在哺乳动物系统细胞中的细胞毒性和促炎作用，以及ChSeco在神经元细胞中的信号传导及其在阿尔茨海默病病理学中的意义。
