کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2020029 1542245 2008 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Characterization of N,N,-dimethyl-d-erythro-sphingosine-induced apoptosis and signaling in U937 cells: Independence of sphingosine kinase inhibition
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Characterization of N,N,-dimethyl-d-erythro-sphingosine-induced apoptosis and signaling in U937 cells: Independence of sphingosine kinase inhibition
چکیده انگلیسی

In the present study, we studied N,N-dimethyl-d-erythro-sphingosine (DMS)-induced cell death and its signaling mechanism in U937 human monocytes. We found that DMS induced cell death in a concentration-dependent manner, while sphingosine 1-phoshate did not. DMS also induced DNA fragmentation, nuclear disruption, and cytochrome c release from mitochondria in a concentration- and time-dependent manner, implying apoptotic cell death. DMS was found to increase mitochondrial membrane potential (MMP) immediately after addition of DMS and to decrease MMP at 2 h after addition. However, sphingosine kinase inhibitors and PKC inhibitors did not induce cell death in U937 cells, a result that appears to exclude sphingosine kinase and PKC as target molecules of DMS in the cell death induction process. Furthermore, DMS modulated the activity of several signaling molecules. DMS induced activation of JNK and p38 MAP kinase, while it decreased the activity of ERK and Akt kinase. However, decrease of MMP, inhibition of JNK, p38 MAP kinase, ERK, or Akt with specific inhibitors could not mimic the DMS-induced cell death, implying multiple concerted processes are involved in DMS-induced cell death. In summary, DMS induced apoptotic cell death via modulation of MMP, JNK, p38 MAP kinase, ERK, and Akt kinase, but not through inhibition of sphingosine kinase or PKC in U937 cells.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Prostaglandins & Other Lipid Mediators - Volume 86, Issues 1–4, June 2008, Pages 18–25
نویسندگان
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