Tissue transglutaminase in cell death

Prematurely born babies are often treated with glucocorticoids. We studied the consequences of an early postnatal and short dexamethasone treatment (0.1–0.01 μg/g, days 1–4) on lung development in rats, focusing on its influence on peaks of cell proliferation around day 4 and of programmed cell death at days 19–21. By morphological criteria, we observed a dexamethasone-induced premature maturation of the septa ( day 4), followed by a transient septal immatureness and delayed alveolarization leading to complete rescue of the structural changes. The numbers of proliferating (anti-Ki67) and dying cells (TdT-mediated dUTP nick end labeling) were determined and compared with controls. In dexamethasone-treated animals, both the peak of cell proliferation and the peak of programmed cell death were reduced to baseline, whereas the expression of tissue transglutaminase (transglutaminase-C), another marker for postnatal lung maturation, was not significantly altered. We hypothesize that a short neonatal course of dexamethasone leads to severe but transient structural changes of the lung parenchyma and influences the balance between cell proliferation and cell death even in later stages of lung maturation.

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Importance of Tissue Transglutaminase in Repair of Extracellular Matrices and Cell Death of Dermal Fibroblasts After Exposure to a Solarium Ultraviolet A Source

Journal of Investigative Dermatology ◽

10.1046/j.1523-1747.2003.12353.x ◽

2003 ◽

Vol 121 (2) ◽

pp. 412-423 ◽

Cited By ~ 26

Author(s):

Stephane R. Gross ◽

Zita Balklava ◽

Martin Griffin

Keyword(s):

Cell Death ◽

Tissue Transglutaminase ◽

Dermal Fibroblasts ◽

Extracellular Matrices ◽

Ultraviolet A

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Tissue transglutaminase and apoptosis: sense and antisense transfection studies with human neuroblastoma cells

Molecular and Cellular Biology ◽

10.1128/mcb.14.10.6584-6596.1994 ◽

1994 ◽

Vol 14 (10) ◽

pp. 6584-6596

Author(s):

G Melino ◽

M Annicchiarico-Petruzzelli ◽

L Piredda ◽

E Candi ◽

V Gentile ◽

...

Keyword(s):

Cell Death ◽

Structural Changes ◽

Tissue Transglutaminase ◽

Neuroblastoma Cell ◽

Neuroblastoma Cells ◽

Neuroblastoma Cell Line ◽

Human Neuroblastoma Cell ◽

Human Neuroblastoma ◽

Transfected Cells ◽

Protein Levels

In this report, we show that the overexpression of tissue transglutaminase (tTG) in the human neuroblastoma cell line SK-N-BE(2) renders these neural crest-derived cells highly susceptible to death by apoptosis. Cells transfected with a full-length tTG cDNA, under the control of a constitutive promoter, show a drastic reduction in proliferative capacity paralleled by a large increase in cell death rate. The dying tTG-transfected cells exhibit both cytoplasmic and nuclear changes characteristic of cells undergoing apoptosis. The tTG-transfected cells express high Bcl-2 protein levels as well as phenotypic neural cell adhesion molecule markers (NCAM and neurofilaments) of cells differentiating along the neuronal pathway. In keeping with these findings, transfection of neuroblastoma cells with an expression vector containing segments of the human tTG cDNA in antisense orientation resulted in a pronounced decrease of both spontaneous and retinoic acid (RA)-induced apoptosis. We also present evidence that (i) the apoptotic program of these neuroectodermal cells is strictly regulated by RA and (ii) cell death by apoptosis in the human neuroblastoma SK-N-BE(2) cells preferentially occurs in the substrate-adherent phenotype. For the first time, we report here a direct effect of tTG in the phenotypic maturation toward apoptosis. These results indicate that the tTG-dependent irreversible cross-linking of intracellular protein represents an important biochemical event in the induction of the structural changes featuring cells dying by apoptosis.

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Cell cycle kinetics, tissue transglutaminase and programmed cell death (apoptosis)

FEBS Letters ◽

10.1016/0014-5793(92)81392-y ◽

1992 ◽

Vol 311 (2) ◽

pp. 174-178 ◽

Cited By ~ 29

Author(s):

S. El Alaoui ◽

S. Mian ◽

J. Lawry ◽

G. Quash ◽

M. Griffin

Keyword(s):

Cell Cycle ◽

Cell Death ◽

Programmed Cell Death ◽

Tissue Transglutaminase ◽

Cell Cycle Kinetics

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Stem cell factor and leukemia inhibitory factor promote primordial germ cell survival by suppressing programmed cell death (apoptosis)

Development ◽

10.1242/dev.118.4.1089 ◽

1993 ◽

Vol 118 (4) ◽

pp. 1089-1094 ◽

Cited By ~ 8

Author(s):

M. Pesce ◽

M.G. Farrace ◽

M. Piacentini ◽

S. Dolci ◽

M. De Felici

Keyword(s):

Cell Death ◽

Stem Cell ◽

Programmed Cell Death ◽

Leukemia Inhibitory Factor ◽

Stem Cell Factor ◽

Tissue Transglutaminase ◽

Primordial Germ Cell ◽

Inhibitory Factor ◽

High Level

Proliferating primordial germ cells (PGCs) isolated from mouse embryos soon after their arrival in the genital ridges would only survive in vitro at temperature of less than 30 degrees C (De Felici, M. and McLaren, A. (1983). Exp. Cell. Res. 144, 417–427; Wabik-Sliz, B. and McLaren, A. (1984). Exp. Cell. Res. 154, 530–536) or when co-cultured on cell feeder layers (Donovan, P. J., Stott, D., Godin, I., Heasman, J. and Wylie, C. C. (1986). Cell 44, 831–838; De Felici, M. and Dolci, S. (1991). Dev. Biol. 147, 281–284). In the present paper we report that mouse PGC death in vitro occurs with all the hallmarks of programmed cell death or apoptosis. We found that after 4–5 hours in culture many PGCs isolated from 12.5 dpc fetal gonads assumed a nuclear morphology and produced membrane bound fragments (apoptotic bodies) typical of apoptotic cells. In addition, PGCs in culture accumulated high level of tissue transglutaminase (tTGase; an enzyme that is induced and activated during apoptosis) and showed extensive degradation of DNA to oligonucleosomal fragments, which is characteristic of apoptosis. The physiological relevance of this mechanism of PGC death is supported by the finding that some PGCs undergoing apoptosis, as revealed by the high level of tTGase expression, were detected in the embryo. Most importantly, we show that the addition of stem cell factor (SCF) or leukemia inhibitory factor (LIF) to the culture medium, two cytokines known to favour PGC survival and/or proliferation in vitro, markedly reduced the occurrence of apoptosis in PGCs during the first hours in culture.(ABSTRACT TRUNCATED AT 250 WORDS)

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Hormonal Control of “Tissue” Transglutaminase Induction during Programmed Cell Death in Frog Liver

Experimental Cell Research ◽

10.1006/excr.1998.4358 ◽

1999 ◽

Vol 247 (2) ◽

pp. 339-346 ◽

Cited By ~ 8

Author(s):

Loredana Assisi ◽

Francesco Autuori ◽

Virgilio Botte ◽

Maria Grazia Farrace ◽

Mauro Piacentini

Keyword(s):

Cell Death ◽

Programmed Cell Death ◽

Tissue Transglutaminase ◽

Hormonal Control

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Induction of tissue transglutaminase by dexamethasone: its correlation to receptor number and transglutaminase-mediated cell death in a series of malignant hamster fibrosarcomas

Biochemical Journal ◽

10.1042/bj3310105 ◽

1998 ◽

Vol 331 (1) ◽

pp. 105-112 ◽

Cited By ~ 24

Author(s):

Timothy S. JOHNSON ◽

Claire I. SCHOLFIELD ◽

James PARRY ◽

Martin GRIFFIN

Keyword(s):

Cell Death ◽

Cell Damage ◽

Tissue Transglutaminase ◽

Receptor Protein ◽

Mrna Synthesis ◽

Body Formation ◽

Transglutaminase Activity ◽

Receptor Number ◽

Dose Dependent ◽

Hamster Fibrosarcoma

Treatment of the hamster fibrosarcoma cell lines (Met B, D and E) and BHK-21 hamster fibroblast cells with the glucocorticoid dexamethasone led to a powerful dose-dependent mRNA-synthesis-dependent increase in transglutaminase activity, which can be correlated with dexamethasone-responsive receptor numbers in each cell line. Increasing the number of dexamethasone-responsive receptors by transfection of cells with the HG1 glucocorticoid receptor protein caused an increase in transglutaminase activity that was proportional to the level of transfected receptor. In all experiments the levels of the tissue transglutaminase-mediated detergent-insoluble bodies was found to be comparable with increases in transglutaminase activity. Despite an increase in detergent-insoluble body formation, an increase in apoptosis as measured by DNA fragmentation was not found. Incubation of cells with the non-toxic competitive transglutaminase substrate fluorescein cadaverine led to the incorporation of this fluorescent amine into cellular proteins when cells were damaged after exposure to trypsin during cell passage. These cross-linked proteins containing fluorescein cadaverine were shown to be present in the detergent-insoluble bodies, indicating that the origin of these bodies is via activation of tissue transglutaminase after cell damage by trypsinization rather than apoptosis per se,since Met B cells expressing the bcl-2 cDNA were not protected from detergent-insoluble body formation. We describe a novel mechanism of cell death related to tissue transglutaminase expression and cell damage.

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