22(R)-hydroxy Cholesterol

22(R)-hydroxy Cholesterol is an endogenous agonist of the liver X receptor (LXR), with an EC₅₀ value of 325nM ^[1]. The LXRs (LXRα and LXRβ) can regulate the expression of cholesterol 7α-hydroxylase induced by oxidosteroids, and cholesterol 7α-hydroxylase is the rate-limiting enzyme in the classical bile acid synthesis process ^[2]. 22(R)-hydroxy Cholesterol can be used to induce cell differentiation and protect neuronal cells ^[3-4].

In vitro, 22(R)-hydroxy Cholesterol (30nM-3μM; 96h) treatment significantly inhibited the proliferation of LNCaP prostate cancer cells in a dose-dependent manner ^[5]. 22(R)-hydroxy Cholesterol (2μM; 14 days) treatment induced hMSCs cells to exhibit neuronal cell-like characteristics, increasing the average cell area, the length of neurites and axons, and increasing the expression of dopamine neuron cell-specific proteins and the percentage of MAP2-positive cells ^[6].

References:
[1] Spencer, T.A., Dansu, L., Russel, J.S., et al. Pharmacophore analysis of the nuclear oxysterol receptor LXRα. J. Med. Chem. 44(6), 886-897 (2001).
[2] Repa, J.J., Turley, S.D., Lobaccaro, J.-M.A., et al. Regulation of absorption and ABC1-mediated efflux of cholesterol by RXR heterodimers. Science 289(5484), 1524-1529 (2000).
[3] Yao Z X, Han Z, Xu J, et al. 22R-Hydroxycholesterol induces differentiation of human NT2 precursor (Ntera2/D1 teratocarcinoma) cells[J]. Neuroscience, 2007, 148(2): 441-453.
[4] Yao Z X, Brown R C, Teper G, et al. 22R‐Hydroxycholesterol protects neuronal cells from β‐amyloid‐induced cytotoxicity by binding to β‐amyloid peptide[J]. Journal of neurochemistry, 2002, 83(5): 1110-1119.
[5] Chuu C P, Lin H P. Antiproliferative effect of LXR agonists T0901317 and 22 (R)-hydroxycholesterol on multiple human cancer cell lines[J]. Anticancer research, 2010, 30(9): 3643-3648.
[6] Singh M, Jain M, Bose S, et al. 22 (R)-hydroxycholesterol for dopaminergic neuronal specification of MSCs and amelioration of Parkinsonian symptoms in rats[J]. Cell death discovery, 2021, 7(1): 13.

22(R)-hydroxy Cholesterol是一种肝X受体（LXR）的内源性激动剂，其EC₅₀值为325nM ^[1]。LXRs（LXRα和LXRβ）能调节由氧化固醇诱导的胆固醇7α-hydroxylase的表达，而胆固醇7α-hydroxylase是经典胆汁酸合成过程中的限速酶 ^[2]。22(R)-hydroxy Cholesterol可用于诱导细胞分化和保护神经元细胞 ^[3-4]。

在体外，22(R)-hydroxy Cholesterol（30nM-3μM; 96h）处理以剂量依赖性方式显著抑制了LNCaP前列腺癌细胞的增殖 ^[5]。22(R)-hydroxy Cholesterol（2μM; 14 days）处理诱导hMSCs细胞产生神经元细胞样特征，增加了细胞的平均面积、神经突和轴突长度，并增加多巴胺能神经元细胞特异性蛋白的表达和MAP2阳性细胞的百分比 ^[6]。