Galectin-1 induces nuclear translocation of endonuclease G in caspase- and cytochrome c-independent T cell death

Hahn, Hejin P.; Pang, Mabel; He, Jiale; Hernandez, Joseph D.; Yang, Ri Yao; Li, Lily Y.; Wang, Xiaodong; Liu, Fu‐Tong; Baum, Linda G.

doi:10.1038/sj.cdd.4401485

Cited by 127 publications

(127 citation statements)

References 58 publications

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“…Besides regulation of cell cycle, exogenously added Gal‐1 also exerts effects through interaction with integrins (Astorgues‐Xerri et al, 2014; Moiseeva et al, 2003), such as activating proapoptotic α5β1‐integrin signaling (Sanchez‐Ruderisch et al, 2011). Gal‐1‐induced apoptosis involves several intracellular mediators including the transcription factor AP1 and the downregulation of Bcl2 protein production (Hahn et al, 2004; Rabinovich et al, 2000; Walzel et al, 2000). Taking into account that α5β1 integrin is an important mediator of microglial activation (Milner et al, 2007), cell surface presentation of Gal‐1 may be implicated in the α5β1‐integrin signaling also leading to death of microglia, consistent with our in vitro observations.…”

Section: Discussionmentioning

confidence: 99%

Astrocyte reactivity after brain injury—: The role of galectins 1 and 3

Sirko

Irmler

Gascón

et al. 2015

Glia

115

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Astrocytes react to brain injury in a heterogeneous manner with only a subset resuming proliferation and acquiring stem cell properties in vitro. In order to identify novel regulators of this subset, we performed genomewide expression analysis of reactive astrocytes isolated 5 days after stab wound injury from the gray matter of adult mouse cerebral cortex. The expression pattern was compared with astrocytes from intact cortex and adult neural stem cells (NSCs) isolated from the subependymal zone (SEZ). These comparisons revealed a set of genes expressed at higher levels in both endogenous NSCs and reactive astrocytes, including two lectins—Galectins 1 and 3. These results and the pattern of Galectin expression in the lesioned brain led us to examine the functional significance of these lectins in brains of mice lacking Galectins 1 and 3. Following stab wound injury, astrocyte reactivity including glial fibrillary acidic protein expression, proliferation and neurosphere‐forming capacity were found significantly reduced in mutant animals. This phenotype could be recapitulated in vitro and was fully rescued by addition of Galectin 3, but not of Galectin 1. Thus, Galectins 1 and 3 play key roles in regulating the proliferative and NSC potential of a subset of reactive astrocytes. GLIA 2015;63:2340–2361

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Section: Discussionmentioning

confidence: 99%

Astrocyte reactivity after brain injury—: The role of galectins 1 and 3

Sirko

Irmler

Gascón

et al. 2015

Glia

115

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“…Even though the signaling pathways responsible for exGal-1 driven T-cell apoptosis have largely been mapped [6,7,[36][37][38], many questions about the exact mechanism by which the cells were sensitized by inGal-1 to exGal-1 mediated apoptosis remain to be elucidated. While the anti-apoptotic effect of intracellular Gal-3 can be explained by the Bcl-2 homolog motif of the protein [39], Gal-1 does not have a homologous segment with any known apoptotic protein, and thus its function in apoptosis must stem from a yet unknown mechanism.…”

Section: Discussionmentioning

confidence: 99%

Novel role for galectin-1 in T-cells under physiological and pathological conditions

Deák¹,

Hornung²,

Novák³

et al. 2015

Immunobiology

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Secreted, extracellular galectin-1 (exGal-1) but not intracellular Gal-1 (inGal-1) has been described as a strong immunosuppressive protein due to its major activity of inducing apoptosis of activated T-cells. It has previously been reported that T-cells express Gal-1 upon activation, however its participation in T-cell functions has remained largely elusive. To determine function of Gal-1 expressed by activated Tcells we have carried out a series of experiments. We have shown that Gal-1, expressed in Gal-1-transgenic Jurkat cells or in activated T-cells, remained intracellularly indicating that Gal-1-induced T-cell death was not a result of an autocrine effect of the de novo expressed Gal-1. Rather, a particular consequence of the inGal-1 expression was that T-cells became more sensitive to exGal-1 added either as a soluble protein or bound to the surface of a Gal-1-secreting effector cell. This was also verified when the susceptibility of activated T-cells from wild type or Gal-1 knockout mice to Gal-1-induced apoptosis were compared. Murine T-cells expressing Gal-1 were more sensitive to the cytotoxicity of the exGal-1 than their Gal-1 knockout counterparts. We also conducted a study with activated T-cells from patients with systemic lupus erythematosus (SLE), a disease in which dysregulated T-cell apoptosis has been well described. SLE T-cells expressed lower amounts of Gal-1 than healthy T-cells and were less sensitive to exGal-1. These results suggested a novel role of inGal-1 in T-cells as a regulator of T-cell response to exGal-1, and its likely contribution to the mechanism in T-cell apoptosis deficiency in lupus.

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“…14 How to explain that only a minority of human melanoma areas show positive correlation between gal-1 expression and TAL apoptosis? There is extensive evidence 13,15,30,31 for the apoptotic role of gal-1 in thymocytes and activated lymphocytes expressing the required glycosyltransferases that modulate the modification of CD45 core 2-O-glycans. 32 However, the lack of correlation found in this report was not due to the absence of sensitive lymphocytes, because most TALs were CD45RO(ϩ), suggesting that they were indeed resistant to the gal-1 apoptosis signal.…”

Section: Discussionmentioning

confidence: 99%

Galectin-3 Expression Correlates with Apoptosis of Tumor-Associated Lymphocytes in Human Melanoma Biopsies

Zubieta

Furman

Barrio

et al. 2006

The American Journal of Pathology

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The immune system recognizes diverse melanoma antigens. However , tumors can evade the immune response , therefore growing and progressing. It has been reported that galectin-3 and galectin-1 can induce apoptosis of activated lymphocytes. However , there is strong evidence indicating that the regulation of galectins function in the human tumor microenvironment is a complex process that is influenced by diverse biological circumstances. Here , we have investigated 33 biopsies (eight primary and 25 metastases) from 24 melanoma patients (15-72 years old) and describe the correlation between the expression of galectin-3 or galectin-1 and the level of apoptosis of tumor-associated lymphocytes using immunohistochemistry and an in situ nick translation assay. The range of galectin-3-positive tumor cells varied between 0% and 93% and that of galectin-1-positive tumor cells varied between 5% and 97%. In addition, 23 ؎ 27% of tumor-associated lymphocytes were apoptotic. Although our results show a correlation between galectin-3 expression and apoptosis of tumorassociated lymphocytes, we could not find such correlation with galectin-1. Considering the complex process of cancer immunoediting, various interacting factors must be considered.

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Galectin-1 induces nuclear translocation of endonuclease G in caspase- and cytochrome c-independent T cell death

Cited by 127 publications

References 58 publications

Astrocyte reactivity after brain injury—: The role of galectins 1 and 3

Astrocyte reactivity after brain injury—: The role of galectins 1 and 3

Novel role for galectin-1 in T-cells under physiological and pathological conditions

Galectin-3 Expression Correlates with Apoptosis of Tumor-Associated Lymphocytes in Human Melanoma Biopsies

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