Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.4.24.23 (
MMP
)
4,246
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
C2-ceramide, a cell permeable analogue of ceramide [
CER
] markedly reduced mitochondrial membrane potential [
MMP
] in insulin-secreting INS cells, which was followed by a significant accumulation of cytochrome c [Cyt c] into the cytosolic compartment. In a manner akin to
CER
, exposure of these cells to interleukin-1beta [IL-1beta] also resulted in reduction in
MMP
and cytosolic accumulation of Cyt c. Further, long-term exposure of these cells to either
CER
[but not its inactive analogue] or IL-1beta caused a marked reduction in their metabolic viability. However, unlike IL-1beta, which increased nitric oxide [NO] release,
CER
-treatment of INS cells had no effects of
CER
on NO release were demonstrable. Together, these findings suggest that
CER
-induced mitochondrial effects may not be mediated via iNOS gene expression and NO production.
CER
also activated an okadaic acid -sensitive protein phosphatase [CAPP] in the purified mitochondrial fraction, suggesting that CAPP might represent one of the target proteins for
CER
in the beta cell mitochondria. Together, our findings suggest direct detrimental effects of
CER
on mitochondrial function in beta cells leading to their dysfunction and demise via apoptosis. Moreover, our findings provide evidence for a potential difference in the mechanisms underlying
CER
- and IL-1beta-induced mitochondrial defects and apoptotic demise of the effete beta cell.
...
PMID:Ceramide induces mitochondrial abnormalities in insulin-secreting INS-1 cells: potential mechanisms underlying ceramide-mediated metabolic dysfunction of the beta cell. 1613 74
