Role of Ceramide in Mediating the Inhibition of Telomerase Activity in A549 Human Lung Adenocarcinoma Cells

Öğretmen, Besim; Schady, Deborah; Usta, Jinan; Wood, Rachael; Kraveka, Jacqueline M.; Luberto, Chiara; Birbes, Hélène; Hannun, Yusuf A.; Obeid, Lina M.

doi:10.1074/jbc.m100314200

Cited by 111 publications

(106 citation statements)

References 52 publications

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“…Multiple lines of evidence have demonstrated the ability of endogenous ceramide to inhibit telomerase activity in A549 cells [87,88]. Moreover, exogenous C 6 -ceramide was also shown to inhibit telomerase, but interestingly, it was found that these actions are due to generation of endogenous ceramide in a process that requires recycling of the sphingosine backbone of C 6 -ceramide through deacylation followed by reacylation to mainly C 16:0 ceramide [18].…”

Section: -3 Telomerase Activity and Recycling Of Short-chain Ceramidementioning

confidence: 99%

The sphingolipid salvage pathway in ceramide metabolism and signaling

Kitatani

Idkowiak‐Baldys

Hannun

2008

Cellular Signalling

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526

457

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Sphingolipids are important components of eukaryotic cells, many of which function as bioactive signaling molecules. Of these, ceramide is a central metabolite and plays key roles in a variety of cellular responses, including regulation of cell growth, viability, differentiation, and senescence. Ceramide is composed of the long-chain sphingoid base, sphingosine, in N-linkage to a variety of acyl groups. Sphingosine serves as the product of sphingolipid catabolism, and it is mostly salvaged through re-acylation, resulting in the generation of ceramide or its derivatives. This recycling of sphingosine is termed the "salvage pathway", and recent evidence points to important roles for this pathway in ceramide metabolism and function. A number of enzymes are involved in the salvage pathway, and these include sphingomyelinases, cerebrosidases, ceramidases, and ceramide synthases. Recent studies suggest that the salvage pathway is not only subject to regulation, but it also modulates the formation of ceramide and subsequent ceramide-dependent cellular signals. This review focuses on the salvage pathway in ceramide metabolism, its regulation, its experimental analysis, and emerging biological functions.

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Section: -3 Telomerase Activity and Recycling Of Short-chain Ceramidementioning

confidence: 99%

The sphingolipid salvage pathway in ceramide metabolism and signaling

Kitatani

Idkowiak‐Baldys

Hannun

2008

Cellular Signalling

Self Cite

526

457

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“…One microgram of total RNA, isolated using an RNA isolation kit (Qiagen, Valencia, CA), was used in reverse transcription reactions as described (22). The resulting total cDNA was then used in the quantitative real-time PCR (Q-RT-PCR) to measure the mRNA levels using TaqMan gene expression kit (Applied Biosystems, Foster City, CA) with ABI 7300 Q-PCR system.…”

Section: Cell Lines and Culture Conditionsmentioning

confidence: 99%

“…The protein levels of human LASS1 and LASS6 were detected by Western blotting using mouse polyclonal antibodies (Abnova) as described previously (22).…”

Section: Cell Lines and Culture Conditionsmentioning

confidence: 99%

“…The levels of active caspase-3, caspase-8, or caspase-9 were also measured by Western blotting using antibodies against caspase-3 (Trevigen, Gaithersburg, MD), caspase-8, and caspase-9 (Cell Signaling Technology, Danvers, MA) as described previously (22). The active caspase-3 levels were also measured by immunofluorescence using active caspase-3 -specific antibody as described by the manufacturer.…”

Section: In Vitromentioning

confidence: 99%

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Role of human longevity assurance gene 1 and C18-ceramide in chemotherapy-induced cell death in human head and neck squamous cell carcinomas

Senkal¹,

Ponnusamy²,

Rossi³

et al. 2007

Molecular Cancer Therapeutics

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149

126

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In this study, quantitative isobologram studies showed that treatment with gemcitabine and doxorubicin, known inducers of ceramide generation, in combination, supraadditively inhibited the growth of human UM-SCC-22A cells in situ. Then, possible involvement of the human homologue of yeast longevity assurance gene 1 (LASS1)/ C 18 -ceramide in chemotherapy-induced cell death in these cells was examined. Gemcitabine/doxorubicin combination treatment resulted in the elevation of mRNA and protein levels of LASS1 and not LASS2-6, which was consistent with a 3.5-fold increase in the endogenous (dihydro)ceramide synthase activity of LASS1 for the generation of C 18 -ceramide. Importantly, the overexpression of LASS1 (both human and mouse homologues) enhanced the growth-inhibitory effects of gemcitabine/ doxorubicin with a concomitant induction of caspase-3 activation. In reciprocal experiments, partial inhibition of human LASS1 expression using small interfering RNA

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“…Telomerase downregulators include the estrogen analogue tamoxifen, 12 differentiation inducers such as retinoic acid, 13,14 DNA-interacting agents daunorubicin, doxorubicin and cisplatin. [15][16][17][18][19][20] However, some of these drugs have complex effects on telomerase activity in treated cells. For example, human testicular cancer cells treated with lethal doses (100 m) of the DNA cross-linker cisplatin exhibit decreased telomerase activity.…”

Section: Introductionmentioning

confidence: 99%

Rapid upregulation of telomerase activity in human leukemia HL-60 cells treated with clinical doses of the DNA-damaging drug etoposide

2002

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The enzyme telomerase is implicated in cellular resistance to apoptosis, but the mechanism for this resistance remains to be elucidated. The ability of telomerase to synthesize new DNA at telomeres suggests that this enzyme might function in the repair of double-stranded DNA breaks. To distinguish the effects of double-stranded DNA break damage and apoptosis on human telomerase activity, we treated the HL-60 human hematopoietic cancer cell line with clinical doses of the chemotherapeutic drug etoposide (0.5 to 5 M), which allowed us to distinguish between events associated with DNA damageinduced cell cycle arrest, and events associated with apoptosis. Large (three-to seven-fold) upregulation of telomerase activity occurred soon after etoposide treatment (3 h) in S/G2/M-arresting populations; this upregulation was abolished at onset of apoptotic cell death. No upregulation of telomerase activity was observed in cells treated with a larger dose of etoposide (5 M) that caused cells to undergo rapid apoptosis without intervening cell cycle arrests. These observations are consistent with a possible role for telomerase upregulation during the DNA damage response.

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Role of Ceramide in Mediating the Inhibition of Telomerase Activity in A549 Human Lung Adenocarcinoma Cells

Cited by 111 publications

References 52 publications

The sphingolipid salvage pathway in ceramide metabolism and signaling

The sphingolipid salvage pathway in ceramide metabolism and signaling

Role of human longevity assurance gene 1 and C18-ceramide in chemotherapy-induced cell death in human head and neck squamous cell carcinomas

Rapid upregulation of telomerase activity in human leukemia HL-60 cells treated with clinical doses of the DNA-damaging drug etoposide

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