Large changes in NAD levels associated with CD38 expression during HL-60 cell differentiation
| Autor: | Zainab N. Al-Abady, Richard A. Billington, A. John Moody, Barbara Durante |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Cell physiology
Biophysics HL-60 Cells CD38 Biology Biochemistry Cofactor immune system diseases hemic and lymphatic diseases Humans RNA Messenger Molecular Biology chemistry.chemical_classification Cell Differentiation hemic and immune systems Cell Biology NAD ADP-ribosyl Cyclase 1 Leukemia Lymphocytic Chronic B-Cell Cell biology Enzyme chemistry Second messenger system biology.protein NAD+ kinase Intracellular Homeostasis |
| Zdroj: | Biochemical and Biophysical Research Communications. 442:51-55 |
| ISSN: | 0006-291X |
| Popis: | NAD is an important cofactor involved in multiple metabolic reactions and as a substrate for several NAD-dependent signalling enzymes. One such enzyme is CD38 which, alongside synthesising Ca(2+)-releasing second messengers and acting as a cell surface receptor, has also been suggested to play a key role in NAD(+) homeostasis. CD38 is well known as a negative prognostic marker in B-CLL but the role of its enzymatic activity has not been studied in depth to date. We have exploited the HL-60 cell line as a model of inducible CD38 expression, to investigate CD38-mediated regulation intracellular NAD(+) levels and the consequences of changes in NAD(+) levels on cell physiology. Intracellular NAD(+) levels fell with increasing CD38 expression and this was reversed with the CD38 inhibitor, kuromanin confirming the key role of CD38 in NAD(+) homeostasis. We also measured the consequences of CD38 expression during the differentiation on a number of functions linked to NAD(+) and we show that some but not all NAD(+)-dependent processes are significantly affected by the lowered NAD(+) levels. These data suggest that both functional roles of CD38 might be important in the pathogenesis of B-CLL. |
| Databáze: | OpenAIRE |
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