Background
C16 ceramide (d18:1/16:0), as an endogenous ceramide, generated by ceramide synthase 6 (CerS6), that acts as a lipid second messenger to regulate apoptosis and stress signaling[1]. C16-ceramide plays a pivotal role in inducing insulin resistance[2].
In vitro, treatment with 100 μM synthetic C16 ceramide (d18:1/16:0), or accumulation of C16 ceramide (d18:1/16:0) through PPMP (30 μM) (namely, a selective inhibitor of glucosylceramide synthase) or MAPP (50 μM) (namely, a specific ceramidase inhibitor) induces apoptosis in neutrophil cultures via caspase-3 activation[3]. In vitro, 12 μM C16-ceramide treatment in HCT116 cells induces EMD (emerin) phosphorylation[4]. In vitro, 1 μM C16 ceramide partially rescued the LASP1-actin (play a role in cell migration) interaction under a CERS6 silencing condition[5]. Exogenous C16-ceramide (20 μM) and acid sphingomyelinase induced trophoblast apoptosis, an effect abrogated completely by cotreatment with 10 ng/ml EGF(epidermal growth factor)[6].
参考文献:
[1]White-Gilbertson S, et al. Ceramide synthase 6 modulates TRAIL sensitivity and nuclear translocation of active caspase-3 in colon cancer cells. Oncogene. 2009 Feb 26;28(8):1132-41.
[2]Chathoth S, et al. Insulin resistance induced by de novo pathway-generated C16-ceramide is associated with type 2 diabetes in an obese population. Lipids Health Dis. 2022 Feb 20;21(1):24.
[3]Seumois G, et al. De novo C16- and C24-ceramide generation contributes to spontaneous neutrophil apoptosis. J Leukoc Biol. 2007 Jun;81(6):1477-86.
[4]Deroyer C, et al. New role for EMD (emerin), a key inner nuclear membrane protein, as an enhancer of autophagosome formation in the C16-ceramide autophagy pathway. Autophagy. 2014 Jul;10(7):1229-40.
[5]Payne SG, et al. Epidermal growth factor inhibits ceramide-induced apoptosis and lowers ceramide levels in primary placental trophoblasts. J Cell Physiol. 1999 Aug;180(2):263-70.
C16 神经酰胺(d18:1/16:0)是一种内源性神经酰胺,由神经酰胺合成酶 6(CerS6)生成,作为脂质第二信使调控细胞凋亡和应激信号[1]。C16 神经酰胺在诱导胰岛素抵抗中起着关键作用[2]。
在体外,用 100 μM 合成 C16 神经酰胺(d18:1/16:0)处理细胞,或通过 PPMP(30 μM)即一种葡萄糖甘油酰胺合成酶选择性抑制剂)或 MAPP(50 μM)(即一种特异性神经酰胺酶抑制剂) 积累的C16 神经酰胺(d18:1/16:0),可通过 caspase-3 激活诱导中性粒细胞凋亡[3]。在体外,用12 μM C16 神经酰胺处理 HCT116 细胞可诱导 EMD(emerin)磷酸化[4]。在体外,1 μM C16 神经酰胺可部分缓解 CERS6 沉默条件下 LASP1 与肌动蛋白(在细胞迁移中发挥作用)之间的相互作用[5]。外源性C16-神经酰胺(20 μM )和酸性鞘磷脂酶可诱导滋养细胞凋亡,与 10 毫微克/毫升 EGF(表皮生长因子)共处理可完全消除这种效应[6]。
Protocol
| Cell experiment [1]: |
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Cell lines
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SW620 cells
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Preparation Method
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Exogenous C16 ceramide sensitizes tumor cell to Fas-mediated apoptosis. SW620 cells were treated with C16 ceramide for 1 h at the indicated concentrations (0 - 3 μM ), and then cultured in the absence or presence of FasL for approximately 24 h.
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Reaction Conditions
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0 - 3 μM; 24h
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Applications
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Exogenous C16 ceramide directly induced apoptosis in a dose-dependent manner, albeit at a low level, exogenous C16 ceramide significantly increased SW620 cell sensitivity to FasL-induced apoptosis。
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| Animal experiment [2]: |
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Animal models
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Male C57BL/6J mice
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Preparation Method
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Mice received repeated DH (the dorsal hippocampus) or BLA (the basolateral amygdala) infusions of vehicle, C8 ceramide ((d18:1/8:0); 2 μM/0.2 μL/side), C16 ceramide ((d18:1/16:0); 2 μM/0.2 μL/side), or C20 ceramide ((d18:1/20:0); 2 μM/0.2 μL/side).
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Dosage form
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2 μM/0.2 μL/side; Intracerebral infusions.
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Applications
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C16 ceramide induced a depressive-like phenotype when infused into the DH(the dorsal hippocampus), but a predominantly non-social anxiogenic-like phenotype when infused into the BLA(the basolateral amygdala).
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参考文献:
[1] Paschall AV, et al. Ceramide targets xIAP and cIAP1 to sensitize metastatic colon and breast cancer cells to apoptosis induction to suppress tumor progression. BMC Cancer. 2014 Jan 15;14:24.
[2] Zoicas I, et al. Ceramides affect alcohol consumption and depressive-like and anxiety-like behavior in a brain region- and ceramide species-specific way in male mice. Addict Biol. 2020 Nov;25(6):e12847.
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