C2 Ceramide is a short-chain cell-permeable ceramide analogue that inhibits the protein Bcl2 phosphorylation with an IC50 value of 14μmol/L [1]. C2 Ceramide serves as an effective research tool for tumor cell apoptosis studies because C2 Ceramide can activate apoptosis in nearly all cell types[2].
In vitro, C2 Ceramide exhibited the IC50 value of 39µmol/L toward HEp-2 cells for 24h[3]. C2 Ceramide caused the inhibition of HERG potassium channel current in HEK293 cells with an IC50 value of 19.5μmol/L after 10h treatment[4]. C2 Ceramide (25μmol/L, 1h) inhibited the mRNA levels and promoter activities of MMP-1, MMP-3 and MMP-9 in U87MG glioma cells, and suppressed cell migration[5]. The application of C2 Ceramide at a concentration of 50μmol/L for 60 minutes blocked the production of reactive oxygen species triggered by hydrogen peroxide and prevented the resulting cell death in rat primary astrocytes[6].
In vivo, C2 Ceramide treatment at 2.0mg/kg by intraperitoneal injection with Long Evans rat pups for 25 days alleviated the symptoms of hyperglycemia, hyperlipidemia and mild steatohepatitis, reduced the lipid content in the brain, and increased the ceramide levels in the liver, brain and serum[7]. The administration of 120μmol/L C2 Ceramide by gavage for 12 hours resulted in a significant reduction of mRNA and protein expression levels of HNF-1 and GSTA1 in the liver of adult male Kunming mice with acetaminophen-induced acute liver injury[8].
References:
[1] Ruvolo P P, Deng X, Ito T, et al. Ceramide induces Bcl2 dephosphorylation via a mechanism involving mitochondrial PP2A[J]. Journal of Biological Chemistry, 1999, 274(29): 20296-20300.
[2] Wagenknecht B, Roth W, Gulbins E, et al. C2-ceramide signaling in glioma cells: synergistic enhancement of CD95-mediated, caspase-dependent apoptosis[J]. Cell Death & Differentiation, 2001, 8(6): 595-602.
[3] Oğuz O, Manole F, Bayar Muluk N, et al. Effects of ceramide C2 application on human laryngeal carcinoma cells: a cell culture study[J]. Eur Rev Med Pharmacol Sci, 2023, 27(5 Suppl): 109-120.
[4] Bai Y, Wang J, Shan H, et al. Sphingolipid metabolite ceramide causes metabolic perturbation contributing to HERG K+ channel dysfunction[J]. Cellular Physiology and Biochemistry, 2007, 20(5): 429-440.
[5] Jung J S, Ahn Y H, Moon B I, et al. Exogenous C2 ceramide suppresses matrix metalloproteinase gene expression by inhibiting ROS production and MAPK signaling pathways in PMA-stimulated human astroglioma cells[J]. International Journal of Molecular Sciences, 2016, 17(4): 477.
[6] Jung J S, Choi M J, Ko H M, et al. Short-chain C2 ceramide induces heme oxygenase-1 expression by upregulating AMPK and MAPK signaling pathways in rat primary astrocytes[J]. Neurochemistry international, 2016, 94: 39-47.
[7] de la Monte S M, Tong M, Nguyen V A, et al. Ceramide-mediated insulin resistance and impairment of cognitive-motor functions[J]. Journal of Alzheimer’s Disease, 2010, 21(3): 967-984.
[8] Ma X, Chang Y, Zhang Y, et al. Effects of C2-ceramide and oltipraz on hepatocyte nuclear factor-1 and glutathione S-transferase A1 in acetaminophen-mediated acute mice liver injury[J]. Frontiers in Pharmacology, 2018, 9: 1009.
C2 Ceramide是一种短链细胞渗透性神经酰胺类似物，可抑制Bcl2蛋白的磷酸化，IC50值为14μmol/L[1]。C2 Ceramide可以激活几乎所有细胞类型的凋亡，是肿瘤细胞凋亡研究的有效工具[2]。
在体外，C2 Ceramide对HEp-2细胞处理24小时的IC50值为39µmol/L[3]。C2 Ceramide处理10小时后，可抑制HEK293细胞中的HERG钾通道电流，IC50值为19.5μmol/L[4]。C2 Ceramide（25μmol/L, 1h）抑制U87MG胶质瘤细胞MMP-1、MMP-3和MMP-9 mRNA水平和启动子活性，抑制细胞迁移[5]。C2 Ceramide在50μmol/L浓度下作用60分钟，可阻断大鼠原代星形胶质细胞中由过氧化氢引起的活性氧的产生，防止大鼠原代星形胶质细胞死亡[6]。
在体内，C2 Ceramide以2.0mg/kg剂量腹腔注射处理Long Evans大鼠幼崽25天，可缓解高血糖、高脂血症和轻度脂肪性肝炎症状，降低脑内脂质含量，提高肝、脑和血清中神经酰胺水平[7]。通过灌胃给予120μmol/L C2神经酰胺12小时后，对乙酰氨基酚诱导的急性肝损伤成年昆明雄性小鼠肝脏中HNF-1和GSTA1的mRNA及蛋白表达水平均显著降低[8]。