p38‐MAP kinase activation followed by BIM induction is essential for glucocorticoid‐induced apoptosis in lymphoblastic leukemia cells

Lu, Jianghua; Quearry, Bonnie; Harada, Hisashi

doi:10.1016/j.febslet.2006.05.031

Cited by 91 publications

(105 citation statements)

References 24 publications

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“…It has previously been reported that p38-MAPK activation is essential for GC-induced apoptosis [19,23]. Dex increased the phosphorylation level of p38-MAPK (Fig.…”

Section: Dex Activates P38-mapk In Osteoblastsmentioning

confidence: 61%

“…Previous reports showed that p38-MAPK is involved in apoptosis [14,23] and activated during the GC-induced apoptosis [15,19]. Recent studies demonstrated that p38-MAPK plays many critical roles in apoptosis and survival in osteoblasts [16,17].…”

Section: Discussionmentioning

confidence: 98%

“…Glucocorticoids have been known to have an effect on bone metabolism [1] and to induce apoptosis in osteoblasts [24,25], osteocytes [26], and numerous lymphoid and myeloid tissues [19,23]. Although the effects of GCs in bone remodeling have been reported, the mechanism of GC-induced apoptosis is poorly understood.…”

Section: Discussionmentioning

confidence: 99%

“…The p38-MAPK has been shown to play many important roles in apoptosis and survival in osteoblasts [16,17]. It has recently been found to phosphorylate the GC receptor [18] and cause dexamethasone (Dex)-induced apoptosis in lymphoid cells [19].…”

Section: Introductionmentioning

confidence: 99%

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Glucocorticoid induces apoptosis of osteoblast cells through the activation of glycogen synthase kinase 3β

et al. 2008

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Glucocorticoids (GCs), which play an important role in the normal regulation of bone remodeling, are widely used as anti-inflammatory and chemotherapeutic agents. However, continued exposure to GCs results in osteoporosis, which is partially due to apoptosis of osteoblasts and osteocytes. To understand the mechanism of how GCs induce cell death in osteoblasts, we examined apoptotic effects of dexamethasone (Dex), GC, on MC3T3-E1 osteoblast cells. Results revealed that Dex-induced apoptosis was inhibited by a GC receptor antagonist, mifepristone, and a general caspase inhibitor, Z-VAD-fmk, indicating that Dex induces apoptosis of MC3T3-E1 cells through the pathways involved in GC receptor and caspase. Glycogen synthase kinase 3b (GSK3b) is known to participate in apoptosis signaling in MC3T3-E1 cells. Dex activated both GSK3b and p38-mitogen-activated protein kinase (MAPK). The inhibition of GSK3b by inhibitor (LiCl) or small interference RNA (siRNA) decreased apoptosis. In contrast, the inhibition of p38-MAPK by inhibitor (SB203580) or siRNA did not decrease, but increase apoptosis. These results suggest that Dex-mediated apoptosis of osteoblasts is facilitated by GSK3b, but prevented by p38-MAPK.

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“…It has previously been reported that p38-MAPK activation is essential for GC-induced apoptosis [19,23]. Dex increased the phosphorylation level of p38-MAPK (Fig.…”

Section: Dex Activates P38-mapk In Osteoblastsmentioning

confidence: 61%

Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Glucocorticoid induces apoptosis of osteoblast cells through the activation of glycogen synthase kinase 3β

et al. 2008

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“…Bim's pro-apoptotic activity is stimulated by phosphorylation through pro-apoptotic JNK and p38 MAP kinases and inhibited by phosphorylation through pro-survival ERK [9,16,[32][33][34][35][36]. Besides phosphorylation, increased Bim protein expression is also associated with some forms of apoptosis [16,37]. In this study, we discovered that sodium arsenite-induced apoptosis requires induction of Bim EL transcription and protein expression.…”

Section: Discussionmentioning

confidence: 99%

p38 MAP kinase mediates arsenite-induced apoptosis through FOXO3a activation and induction of Bim transcription

Cai

Xia

2008

Apoptosis

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Sodium arsenite induces apoptosis in PC12 cells by activating the stress-activated p38 MAP kinase and the pro-apoptotic Bcl-2 family protein Bim EL . However, the relationship between p38 and Bim EL in this apoptosis has not been fully defined. Here, we report that sodium arsenite stimulates the protein expression and promoter activity of Bim EL in a p38-dependent manner. Sodium arsenite also caused nuclear translocation of FOXO3a, indicative of FOXO3a activation. Addition of a p38 inhibitor prevented FOXO3a nuclear translocation. RNAi knock down of FOXO3a inhibited Bim promoter activity, Bim EL protein expression, and arsenite-induced apoptosis. Our data identify p38 activation of FOXO3a and subsequent induction of Bim EL expression as a novel apoptotic mechanism. Together with our previous finding that Bim EL is phosphorylated and activated by p38, these results demonstrate that p38 induces apoptosis by regulating Bim EL at both the transcriptional and post-translational levels.

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Gene expression profile analysis of SUDHL6 cells with siRNA‐mediated BCL11A downregulation

Gao

Ding

et al. 2014

Cell Biology International

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Our previous study has shown that downregulation of B-cell chronic lymphocytic leukemia (CLL)/lymphoma11A (BCL11A) gene by small interfering RNA (siRNA) resulted in the growth inhibition and apoptosis of B cell lymphoma cell line SUDHL6. To gain further insight into the molecular mechanisms of this process and identify the differentially expressed genes in SUDHL6 cells after BCL11A downregulation, the global gene expression profile was identified and analyzed using the Affymetrix HG-U133 Plus 2.0 array. Twenty-one differentially expressed genes were validated and analyzed from the BCL11A siRNA-treated SUDHL6 cells. There was a significant dysregulation in the global gene expression of the BCL11A-suppressed SUDHL6 cells. There were 1903 genes differentially expressed with >2-fold changes between the BCL11A siRNA- and negative control-transfected cells. Of these, there were 916 upregulated genes and 987 downregulated genes. The differential genes are involved in various molecular functions and signaling pathways. QRT-PCR validation of the selected differentially expressed genes demonstrated there was a good correlation with the microarray analysis. There was a significant deregulation of expression in the apoptosis-related genes such as BCL-2, BCL2L11 and involved in TGFβ, MAPK, WNT signaling pathways after BCL11A was downregulated in SUDHL6 cells. Our results show that the suppression of BCL11A by RNA interference altered gene expression profile of SUDHL6 cells. The apoptosis-related genes BCL-2, BCL2L11 and the gene alterations in TGFβ, MAPK, WNT signaling pathways might be important in BCL11A siRNA-induced apoptosis of SUDHL6 cells, suggesting BCL11A is involved in gene networks associated with apoptosis.

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p38‐MAP kinase activation followed by BIM induction is essential for glucocorticoid‐induced apoptosis in lymphoblastic leukemia cells

Cited by 91 publications

References 24 publications

Glucocorticoid induces apoptosis of osteoblast cells through the activation of glycogen synthase kinase 3β

Glucocorticoid induces apoptosis of osteoblast cells through the activation of glycogen synthase kinase 3β

p38 MAP kinase mediates arsenite-induced apoptosis through FOXO3a activation and induction of Bim transcription

Gene expression profile analysis of SUDHL6 cells with siRNA‐mediated BCL11A downregulation

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