Ceramides and cell signaling molecules in psoriatic epidermis: reduced levels of ceramides, PKC-alpha, and JNK.
Ceramides are the main lipids in the stratum corneum and are generated during cellular stress and apoptosis by de novo synthesis or by the action of sphingomyelinase. In addition, they are lipid second messengers produced by sphingolipid metabolism and trigger important cell responses, including protein kinase C-alpha (PKC-alpha) activation and the stimulation of signal transduction pathways with apoptosis and stress-activated protein kinases (SAPK), such as c-jun N-terminal kinase (JNK). Thus, ceramides have anti-proliferative and apoptotic effects. This study measured the changes in the levels of epidermal ceramides and ceramide-related apoptotic signaling molecules in psoriasis patients. Samples from lesional and non-lesional epidermis were obtained from psoriasis patients. Total ceramides were fractionated using thin-layer chromatography, and the levels of PKC-alpha and JNK expression were measured using Western blot analysis with specific antibodies. The ceramide level was reduced significantly, and this was associated with the downregulation of apoptotic signaling molecules, such as PKC-alpha and JNK, in the lesional epidermis of psoriasis patients. These results suggest that the decreased level of ceramides downregulates the apoptotic pathway, leading to epidermal proliferation in psoriasis.
Lew
Bark-Lynn
BL
Department of Dermatology, College of Medicine, Kyung Hee University, Seoul, Korea.
Cho
Yunhi
Y
Kim
Jungmin
J
Sim
Woo-Young
WY
Kim
Nack-In
NI
D000328:Adult; D017209:Apoptosis / Q000502:physiology; D015153:Blotting, Western; D002518:Ceramides / Q000378:metabolism*; D002855:Chromatography, Thin Layer; D004817:Epidermis / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D005260:Female; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008297:Male; D051571:Protein Kinase C-alpha / Q000378:metabolism; D011565:Psoriasis / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D012720:Severity of Illness Index; D015398:Signal Transduction / Q000502:physiology*
D002518:Ceramides; D051571:Protein Kinase C-alpha; D048031:JNK Mitogen-Activated Protein Kinases