C18 Ceramide (d18:1/18:0) is an endogenous bioactive sphingolipid produced by the metabolism of Ceramide within cells. It can cross the blood-brain barrier and is the main ceramide produced after damage to the hippocampal region [1-2]. Ceramide is an important signaling sphingolipid involved in cell growth arrest, differentiation, and apoptosis. C18 Ceramide induces cell death, promotes autophagy, and enhances exocytosis through mechanisms such as activating endoplasmic reticulum stress, inhibiting the PI3K/AKT signaling pathway, and affecting lipid raft-related functions [3-4]. C18 Ceramide has anti-cancer functions and can be used in the research of cancer such as glioma and mechanisms of neuronal damage [5].
In vitro, treatment with C18 Ceramide (20μM; 48h) significantly inhibited the cell viability of U251 and A172 glioma cells overexpressing CERS1, induced cell death, and activated endoplasmic reticulum stress, increasing the mRNA and protein levels of ATF-4, XBP-1(s), and CHOP [4]. Treatment with C18 Ceramide (0.01, 0.1, and 10μM; 4d) on osteoclasts and osteoblasts significantly promoted the formation of differentiated osteoblasts, increased the generation of osteoblasts and the expression levels of osteoclast differentiation markers (such as Trap, Ctr, Mmp9, and Catk) [6].
In vivo, C18 Ceramide (5mg/kg/day; 10d; i.p.) treatment significantly alleviated bile-accumulation-induced liver injury (CLI) in wild-type (WT) female mice, increased the level of C18 Ceramide in the liver, and significantly elevated the expression of nuclear Lxrβ and Sult2a1 in liver cells, as well as the mRNA levels of Scd1 and Fasn [7].
References:
[1] Tang N, et al. Differential effects of ceramide species on exocytosis in rat PC12 cells. Exp Brain Res. 2007 Nov;183(2):241-7.
[2] Mizutani, Y., Kihara, A., and Igarashi, Y. Mammalian Lass6 and its related family members regulate synthesis of specific ceramides. Biochem J. 390(Pt. 1), 263-271 (2005).
[3] Chen L, Chen H, Li Y, et al. Endocannabinoid and ceramide levels are altered in patients with colorectal cancer[J]. Oncology reports, 2015, 34(1): 447-454.
[4] Wang Z, et al. Overexpression of ceramide synthase 1 increases C18-ceramide and leads to lethal autophagy in human glioma. Oncotarget. 2017 Oct 23;8(61):104022-104036.
[5] Saddoughi S A, Garrett-Mayer E, Chaudhary U, et al. Results of a phase II trial of gemcitabine plus doxorubicin in patients with recurrent head and neck cancers: serum C18-ceramide as a novel biomarker for monitoring response[J]. Clinical Cancer Research, 2011, 17(18): 6097-6105.
[6] Kim B J, Lee J Y, Park S J, et al. Elevated ceramides 18: 0 and 24: 1 with aging are associated with hip fracture risk through increased bone resorption[J]. Aging (Albany NY), 2019, 11(21): 9388.
[7] Liao L, Liu Z, Liu L, et al. Targeting the ceramidase ACER3 attenuates cholestasis in mice by mitigating bile acid overload via unsaturated ceramide-mediated LXRβ signaling transduction[J]. Nature Communications, 2025, 16(1): 2112.
C18 Ceramide (d18:1/18:0)是Ceramide在细胞内经过代谢产生的一种内源性生物活性鞘脂，可通过血脑屏障，是海马区受损后产生的主要神经酰胺 [1-2]。神经酰胺是参与细胞生长停滞、分化和细胞凋亡的重要信号鞘脂。C18 Ceramide通过激活内质网应激、抑制PI3K/AKT信号通路以及影响脂质筏相关功能等机制，诱导细胞死亡、促进自噬、增强胞吐 [3-4]。C18 Ceramide具有抑癌功能，可用于胶质瘤等癌症和神经元损伤机制研究 [5]。
在体外，C18 Ceramide (20μM; 48h)处理显著抑制了CERS1过表达的U251和A172胶质瘤细胞的细胞活力，诱导细胞死亡并激活内质网应激，增加了ATF-4、XBP-1(s)和CHOP的mRNA和蛋白水平[4]。C18 Ceramide（0.01、0.1和10μM; 4d）处理破骨细胞和成骨细胞，显著促进了分化成骨细胞的形成，增加成骨细胞的生成和骨吸收细胞分化标志物（如Trap、Ctr、Mmp9和Catk）的表达水平 [6]。
在体内，C18 Ceramide（5mg/kg/day; 10d; i.p.）处理显著减弱了野生型（WT）雌性小鼠的胆汁淤积性肝损伤（CLI），升高了肝脏中C18 Ceramide水平，肝细胞中核Lxrβ、Sult2a1的表达和Scd1、Fasn的mRNA水平也显著升高 [7]。