Transforming Growth Factor-β-Mediated Apoptosis in the Ramos B-Lymphoma Cell Line Is Accompanied by Caspase Activation and Bcl-XLDownregulation

Saltzman, Alan; Munro, Robin; Searfoss, George H.; Franks, Carol F.; Jaye, Michael; Ivashchenko, Yuri

doi:10.1006/excr.1998.4096

Cited by 91 publications

(74 citation statements)

References 41 publications

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“…Staurosporine had no effect on Bcl-2 expression (data not shown). These data confirm previous data in other cell types that also showed downregulation of Bcl-X L by staurosporine (Giuliano et al, 2004) and other pro-apoptotic stimuli (Liu and Stein, 1997;Saltzman et al, 1998;Weinmann et al, 1999). Furthermore, cell lysates of whole kidneys from SK-2-deficient mice exhibited significantly enhanced protein expression of Bcl-X L ( Figure 4B), but not of Bcl-2 (data not shown).…”

Section: Figuresupporting

confidence: 92%

Sphingosine kinase 1 and 2 regulate the capacity of mesangial cells to resist apoptotic stimuli in an opposing manner

Hofmann

Ren

Schwalm

et al. 2008

BCHM

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Sphingosine kinases (SKs) are key enzymes regulating the production of sphingosine-1-phosphate (S1P), which determines important cell responses including cell growth and death. Here we show that renal mesangial cells isolated from wild-type, SK-1 -/-, and SK-2 -/-mice show a differential response to apoptotic stimuli. Wildtype mesangial cells responded to staurosporine with increased DNA fragmentation and caspase-3 processing, which was enhanced in SK-1 -/-cells. In contrast, SK-2 -/-cells were highly resistant to staurosporine-induced apoptosis. Furthermore, the basal phosphorylation and activity of the anti-apoptotic protein kinase B (PKB) and of its substrate Bad were decreased in SK-1 -/-but not in SK-2 -/-cells. Upon staurosporine treatment, phosphorylation of PKB and Bad decreased in wild-type and SK-1 -/-cells, but remained high in SK-2 -/-cells. In addition, the anti-apoptotic Bcl-X L was significantly upregulated in SK-2 -/-cells, which may further contribute to the protective state of these cells. In summary, our data show that SK-1 and SK-2 have opposite effects on the capacity of mesangial cells to resist apoptotic stimuli. This is due to differential modulation of the PKB/Bad pathway and of Bcl-X L expression. Thus, subtype-selective targeting of SKs will be critical when considering these enzymes as therapeutic targets for the treatment of inflammation or cancer.

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Section: Figuresupporting

confidence: 92%

Sphingosine kinase 1 and 2 regulate the capacity of mesangial cells to resist apoptotic stimuli in an opposing manner

Hofmann

Ren

Schwalm

et al. 2008

BCHM

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“…Concomitant with our studies, others reported that this process involves activation of caspase 3 (24,25) and may involve down-regulation of the Bcl-2 family member Bcl-X L (24) and cleavage of the retinoblastoma protein (pRb). In this study, we show that these aforementioned events are late in TGF-␤1-mediated apoptosis and are preceded by activation of caspases 2, 7, 8, and 9 in a caspase 8-dependent, but caspase 3-independent manner.…”

supporting

confidence: 82%

“…TGF-␤1 pretreatment of primary B cells has been demonstrated to block activation signal-induced proliferation (11)(12)(13)(14) and to inhibit Ig secretion (15)(16)(17), and may promote class switching to an IgA phenotype (18). It has also been suggested that TGF-␤1 can induce apoptosis in human primary B lymphocytes (19 -21) and BL cell lines (20,(22)(23)(24)(25)(26). The induction of apoptosis by TGF-␤1 has also been observed in myeloid leukemia cells (27), gastric carcinoma cells (28), primary endometrial cells (29), primary hepatocytes and hepatoma cells (30), human cervical carcinoma cell lines (31), and human lung epithelial cell lines (32).…”

mentioning

confidence: 99%

Apoptosis Induced by TGF-β1 in Burkitt’s Lymphoma Cells Is Caspase 8 Dependent But Is Death Receptor Independent

Inman

Allday

2000

The Journal of Immunology

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TGF-β is a potent inducer of apoptosis in many Burkitt’s lymphoma (BL) cell lines. In this study, we characterize this apoptotic process in the EBV-negative BL41 cell line. Induction of apoptosis was detected as early as 8 h after TGF-β treatment, as assayed by TUNEL and poly(ADP-ribose) polymerase cleavage. FACS analysis demonstrates that this proceeds predominately from the G1, but also from the G2/M phases of the cell cycle. We observed no early detectable changes in the steady-state levels of Bcl-2 and several of its family members after TGF-β treatment. We detected cleavage of caspases 2, 3, 7, 8, and 9 into their active subunits. Consistent with the involvement of these enzymes in TGF-β-mediated apoptosis, the broad spectrum caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp(Ome)-flouromethylketone (ZVAD-fmk) blocked TGF-β-induced apoptosis and revealed a G1 arrest in treated cells. Use of specific caspase inhibitors revealed that the induction of apoptosis is caspase 8 dependent, but caspase 3 independent. Activation of caspase 8 has been shown to be a critical event in death receptor-mediated apoptosis. However, TGF-β treatment of BL41 cells was found not to affect the cell surface expression of Fas, TNF-R1, DR3, DR4, or DR5, or the steady-state expression levels of Fas ligand, TNF-R1, DR3, DR4, and DR5. Furthermore, blocking experiments indicated that TGF-β-mediated apoptosis is not dependent on Fas ligand, TNF-α, tumor necrosis-like apoptosis-inducing ligand, or TNF-like weak inducer of apoptosis signaling. Therefore, it appears that TGF-β induces apoptosis in BL cell lines via caspase 8 in a death receptor-independent fashion.

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“…It was reported that TGF-β-induced apoptosis is associated with up-regulation of pro-apoptotic molecules such as Bax and p53 and/or with downregulation of anti-apoptotic molecules such as Bcl-2 and Bcl-X L [6], [14], [15]. TGF-b-induced apoptosis in AML-12 cells can be blocked by the inhibition of protein synthesis [33].…”

Section: Disscussionmentioning

confidence: 99%

“…Anti-oxidants, such as vitamin C, can block the TGF-β-induced apoptotic process [12]. Recently, several reports provide evidence showing that TGF-β-induced apoptosis can be mediated by caspases [5], [9], [13], [14]. It has also been reported that TGF-β induces apoptosis through the regulation of the expression of pro-and anti-apoptotic molecules, such as p53, Bax, Bik, Bcl-2, and Bcl-XL [6], [14], [15].…”

Section: Introductionmentioning

confidence: 99%

The involvement of p38 MAPK in transforming growth factor β1-induced apoptosis in murine hepatocytes

et al. 2001

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We reported in this manuscript that TGF-β1 induces apoptosis in AML12 murine hepatocytes, which is associated with the activation of p38 MAPK signaling pathway. SB202190, a specific inhibitor of p38 MAPK, strongly inhibited the TGF-β1-induced apoptosis and PAI-1 promoter activity. Treatment of cells with TGF-β1 activates p38. Furthermore, over-expression of dominant negative mutant p38 also reduced the TGF-β1-induced apoptosis. The data indicate that the activation of p38 is involved in TGF-β1-mediated gene expression and apoptosis.

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Transforming Growth Factor-β-Mediated Apoptosis in the Ramos B-Lymphoma Cell Line Is Accompanied by Caspase Activation and Bcl-XLDownregulation

Cited by 91 publications

References 41 publications

Sphingosine kinase 1 and 2 regulate the capacity of mesangial cells to resist apoptotic stimuli in an opposing manner

Sphingosine kinase 1 and 2 regulate the capacity of mesangial cells to resist apoptotic stimuli in an opposing manner

Apoptosis Induced by TGF-β1 in Burkitt’s Lymphoma Cells Is Caspase 8 Dependent But Is Death Receptor Independent

The involvement of p38 MAPK in transforming growth factor β1-induced apoptosis in murine hepatocytes

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