C2 Ceramide

C2 Ceramide (Ceramide 2) is the main lipid of the stratum corneum and a protein phosphatase 1 (PP1) activator. C2 Ceramide activates PP2A and ceramide-activated protein phosphatase (CAPP). C2 Ceramide induces cells differentiation, autophagy and apoptosis, inhibits mitochondrial respiratory chain complex III. C2 Ceramide is also a skin conditioning agent that protects the epidermal barrier from water loss^{[1][2][3][4][5]}. IC50 & Target: Protein phosphatase 1^[2]
PP2A^[4]
Ceramide-activated protein phosphatase (CAPP)^[4]
Apoptosis^[1]
Mitochondrial respiratory chain complex III^[1] In Vitro: C2 Ceramide (5 nM-200 µM; 24 hours; primary mouse osteoblasts) treatment (≤500 nM) promots osteoblast viability, whilst concentrations ≥2 µM significantly reduces osteoblast viability in a dose- and time-dependent manner^[1].
C2 Ceramide increases cytoplasmic histone-associated DNA fragments by 5.7- and 11.2-fold at 50 µM and 100 µM C2 Ceramide concentrations respectively in osteoblasts. At these higher concentrations, C2 Ceramide is a potent inducer of apoptosis in osteoblasts^[1].
C2 Ceramide up-regulates mRNA expression of angiogenic genes in human dental pulp cells (HDPCs) and increases the migration and capillary tube formation of endothelial cells, whereas PP1 small interfering RNA shows opposite effects. Human dental pulp cells (HDPCs) increases levels of bone morphogenetic protein 2, phosphorylation of Smad 1/5/8, and mRNA expression of runt-related transcription factor 2 and osterix^[2]. In Vivo: The PP1 activator C2 Ceramide increases alkaline phosphatase activity, mineralizes nodule formation, and mRNA expression of dentin matrix protein 1 and dentin sialophosphoprotein. In contrast, knockdown by PP1 small interfering RNA inhibits odontoblastic differentiation^[2].