Alterations in cell death and cell cycle progression in the UV-irradiated epidermis of bcl-2-deficient mice

Gillardon, Frank; Moll, Ingrid; Meyer, Michaël; Michaelidis, Theologos M.

doi:10.1038/sj.cdd.4400455

Cited by 27 publications

(23 citation statements)

References 19 publications

(27 reference statements)

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“…The ability of Akt promoting cell survival is generally known to be based on its ability to phosphorylate on residues necessary for their inactivation of several proapoptotic proteins, including Bad, caspase-9, transcription factors of the forkhead family and IKK. [9][10][11][12] We here presented that Bcl-2 overexpression sustained Akt level and its phosphorylation. Although the increase of antiapoptotic effect of Akt was previously demonstrated in Bcl-2 overexpressing cells, any evidence showing direct association between Bcl-2 overexpression and PI3K/Akt signaling pathway has not been elucidated to date.…”

Section: Discussionmentioning

confidence: 85%

“…Overexpression of either of these proteins serves to protect cells against apoptosis induced by such diverse stimuli as viral infection, hypoxia, ionizing radiation or chemotherapeutic agents. [7][8][9][10][11] In vivo and in vitro studies have shown that Bcl-2 regulates intracellular Ca 2+ levels and prevents the loss of mitochondrial membrane potential induced by proapoptotic stimuli. 12 It has been suggested that Bcl-2 may act as an ion channel and regulates the release of cytochrome c from mitochondria.…”

Section: Introductionmentioning

confidence: 99%

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Bcl-2 attenuates anticancer agents-induced apoptosis by sustained activation of Akt/protein kinase B in U937 cells

et al. 2005

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Aberrant overexpression of antiapoptotic members of the Bcl-2 protein family contributes to resistance to anticancer therapeutic drugs. Thus, this protein represent attractive target for novel anticancer agents. In the present study, we determined the effect of the anti-apoptosis protein Bcl-2 on caspase-3 activation, PLC-gamma1 degradation and Akt activation during the various anticancer agents-induced apoptosis. Treatment with chrysin for 12 h produced morphological features of apoptosis in U937 cells, which was associated with caspase-3 activation and PLC-gamma1 degradation. Induction of apoptosis was also accompanied by down-regulation of XIAP and inactivation of Akt. Chrysin-induced caspase-3 activation, PLC-gamma1 degradation and apoptosis were significantly attenuated in Bcl-2 overexpressing U937/Bcl-2 cells. Ectopic expression of Bcl-2 appeared to inhibit ceramide-, and Akt specific inhibitor (SH-6)-induced apoptosis by sustained Akt activation. Thus, our findings imply that some of the biological functions of Bcl-2 may be attributed to their ability to inhibit anticancer agents-induced apoptosis through the sustained Akt activation.

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Section: Discussionmentioning

confidence: 85%

Section: Introductionmentioning

confidence: 99%

Bcl-2 attenuates anticancer agents-induced apoptosis by sustained activation of Akt/protein kinase B in U937 cells

et al. 2005

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“…Rather, galectin-7 operates in vivo as a fine tuner, ensuring the completion of a robust and short apoptotic reaction in response to UVB stress. It is worth noting that this information could only have been obtained by examining the kinetics of the apoptotic response over the (Ziegler et al, 1994;Gillardon et al, 1999;Grossman et al, 2001), would have been misleading. For example, at 12 h post-UVB, the reduced number of apoptotic cells in the mutant mice could have been taken as a proof of a proapoptotic role, whereas the opposite conclusion could have been drawn from the results obtained at 9 h post-UVB.…”

Section: Discussionmentioning

confidence: 99%

Galectin-7 in the Control of Epidermal Homeostasis after Injury

Gendronneau

Sidhu

Delacour

et al. 2008

MBoC

105

131

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Galectins, a family of ␤-galactoside binding lectins, have recently emerged as novel regulators of tissue homeostasis. Galectin-7 is predominantly expressed in stratified epithelia, especially in epidermis. We report here the generation of galectin-7-deficient mice that are viable and do not display phenotypical abnormalities in skin structure or expression of epidermal markers. However, these mice show unique defects in the maintenance of epidermal homeostasis in response to environmental challenges. First, after UVB irradiation in vivo, the apoptotic response is prematurely triggered and lasts longer in the mutant epidermis. This result contrasts with the proapoptotic role that had been proposed for galectin-7. Second, wound-healing experiments in vivo revealed that galectin-7-deficient mice displayed a reduced reepithelialization potential compared with wild-type littermates. This effect could be attributed to a defect in cell migration. Because galectin-7 is located in the podosomes of keratinocytes migrating out of skin explants in culture, we propose that this glycan-binding protein may directly influence cell/extracellular matrix interactions. Finally, we also detected an unexpected intense hyperproliferative reaction consecutive to both types of stress in galectin-7-deficient mice. Together, these studies provide the first genetic evidence showing that galectin-7 can modulate keratinocyte apoptosis, proliferation, and migration during skin repair. INTRODUCTIONGalectins are a family of soluble lectins sharing a unique carbohydrate recognition domain (CRD) that confers specificity for ␤-galactoside derivatives (Barondes et al., 1994a,b). The 15 mammalian members known to date can be classified into three groups on the basis of their structure, namely, "proto-type" galectins containing one CRD domain (14 kDa); galectin-3 (30 kDa), which is a unique chimeric molecule containing a single CRD motif combined with a prolinerich N-terminal domain; and tandem-repeat galectins that are composed of two CRDs separated by a short linker sequence (30 kDa) (Hirabayashi and Kasai, 1993). Despite their lack of signal peptide, galectins can be secreted by an endoplasmic reticulum (ER)-Golgi-independent pathway (Lindstedt et al., 1993;Sato et al., 1993). They can be found both intracellularly (cytoplasm and/or nucleus) and extracellularly depending on the cell type, cell cycle stage, and differentiation state. Galectins can be associated with the plasma membrane, but they do not contain transmembrane domain. Consistent with this variable subcellular location, galectins have been implicated in a wide range of cellular processes, including cell-cell interactions, extracellular matrix remodelling, apoptosis, the cell cycle, intracellular trafficking, and splicing (Hughes, 2001;Liu et al., 2002;Hsu and Liu, 2004;Delacour et al., 2006;Elola et al., 2007). Their roles in cancer biology (Lahm et al., 2004;Takenaka et al., 2004;Liu and Rabinovich, 2005;Thijssen et al., 2007), immune response (Sato and Nieminen, 2004;Rabinovich et a...

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“…44,45 Indeed, the effects of both donor T cells and UV irradiation are pleiotropic. UV irradiation causes acute cell death and local inflammation, [49][50][51][52] and alloreactive T cells induce systemic cytokines and local inflammation in skin and can directly target nonhematopoietic and hematopoietic cells in addition to LCs. Our finding that donor LCs engrafted in Langerin-DTA recipients, which have a very specific loss of only LCs, 23 without the need for allogeneic T cells or UV irradiation indicates that skin inflammation per se is not required for donor LC engraftment.…”

Section: Discussionmentioning

confidence: 99%