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Characterization of distinct sub-cellular location of transglutaminase type II: changes in intracellular distribution in physiological and pathological states.

Piacentini M, D'Eletto M, Farrace MG, Rodolfo C, Del Nonno F, Ippolito G, Falasca L - Cell Tissue Res. (2014)

Bottom Line: Human tissue samples of myocardium and gut mucosa (diseased and healthy) are also analyzed.We describe a possible unrecognized location of TG2.Our findings thus provide useful insights regarding the functions and regulation of this pleiotropic enzyme.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, University of Rome 'Tor Vergata', Rome, Italy.

ABSTRACT
Transglutaminase type II (TG2) is a pleiotropic enzyme that exhibits various activities unrelated to its originally identified functions. Apart from post-translational modifications of proteins (peculiar to the transglutaminase family enzymes), TG2 is involved in diverse biological functions, including cell death, signaling, cytoskeleton rearrangements, displaying enzymatic activities, G-protein and non-enzymatic biological functions. It is involved in a variety of human diseases such as celiac disease, diabetes, neurodegenerative diseases, inflammatory disorders and cancer. Regulatory mechanisms might exist through which cells control multifunctional protein expression as a function of their sub-cellular localization. The definition of the tissue and cellular distribution of such proteins is important for the determination of their function(s). We investigate the sub-cellular localization of TG2 by confocal and immunoelectron microscopy techniques in order to gain an understanding of its properties. The culture conditions of human sarcoma cells (2fTGH cells), human embryonic kidney cells (HEK293(TG)) and human neuroblastoma cells (SK-n-BE(2)) are modulated to induce various stimuli. Human tissue samples of myocardium and gut mucosa (diseased and healthy) are also analyzed. Immuno-gold labeling indicates that TG2 is localized in the nucleus, mitochondria and endoplasmic reticulum under physiological conditions but that this is not a stable association, since different locations or different amounts of TG2 can be observed depending on stress stimuli or the state of activity of the cell. We describe a possible unrecognized location of TG2. Our findings thus provide useful insights regarding the functions and regulation of this pleiotropic enzyme.

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Related in: MedlinePlus

Immuno-gold localization of TG2 in SK-n-BE(2) neuroblastoma cells treated with doxorubicin. The anti-cancer drug doxorubicin causes an extensive distribution of TG2 at the plasma membrane. Gold particles seem to be associated with both dense vesicles (arrowheads) located under the cell surface (a) and with protruding cell processes (b). Bars 0.15 μm
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Fig8: Immuno-gold localization of TG2 in SK-n-BE(2) neuroblastoma cells treated with doxorubicin. The anti-cancer drug doxorubicin causes an extensive distribution of TG2 at the plasma membrane. Gold particles seem to be associated with both dense vesicles (arrowheads) located under the cell surface (a) and with protruding cell processes (b). Bars 0.15 μm

Mentions: A different aspect of TG2 and the extracellular environment relates to cancer cells. TG2 appears to be associated with the early changes in cervical carcinogenesis (Del Nonno et al. 2011) and is involved in epithelial mesenchymal transition, a key step in cancer metastasis (Lin et al. 2011). It has also been reported to be over-expressed in highly aggressive and chemo-resistant human brain, breast, lung and colorectal cancers and to be involved in the migration and invasion of cancer cells such as breast cancer cells and neuroblastomas (Miyoshi et al. 2010; Choi et al. 2011; Oh et al. 2011). Several studies have reported a relationship between TG2 expression and doxorubicin drug resistance but the mechanism has not been fully clarified. Here, the distribution of TG2 was studied in SK-n-BE(2) neuroblastoma cells after doxorubicin treatment (10 μM for 3 h). The immunoelectron microscopic localization showed that treatment with the anti-cancer drug doxorubicin induced a translocation of the enzyme to the cell surface at the level of plasma membrane projections (Fig. 8). Cell surface microvilli displayed numerous microvesicles on their inside; these appeared to be decorated with gold particles indicating the presence of TG2. These observations also provide further insights regarding the possible mechanism utilized by the cell to externalize TG2, suggesting that it is delivered to the surface inside small vesicles (Fig. 8a).Fig. 8


Characterization of distinct sub-cellular location of transglutaminase type II: changes in intracellular distribution in physiological and pathological states.

Piacentini M, D'Eletto M, Farrace MG, Rodolfo C, Del Nonno F, Ippolito G, Falasca L - Cell Tissue Res. (2014)

Immuno-gold localization of TG2 in SK-n-BE(2) neuroblastoma cells treated with doxorubicin. The anti-cancer drug doxorubicin causes an extensive distribution of TG2 at the plasma membrane. Gold particles seem to be associated with both dense vesicles (arrowheads) located under the cell surface (a) and with protruding cell processes (b). Bars 0.15 μm
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4233112&req=5

Fig8: Immuno-gold localization of TG2 in SK-n-BE(2) neuroblastoma cells treated with doxorubicin. The anti-cancer drug doxorubicin causes an extensive distribution of TG2 at the plasma membrane. Gold particles seem to be associated with both dense vesicles (arrowheads) located under the cell surface (a) and with protruding cell processes (b). Bars 0.15 μm
Mentions: A different aspect of TG2 and the extracellular environment relates to cancer cells. TG2 appears to be associated with the early changes in cervical carcinogenesis (Del Nonno et al. 2011) and is involved in epithelial mesenchymal transition, a key step in cancer metastasis (Lin et al. 2011). It has also been reported to be over-expressed in highly aggressive and chemo-resistant human brain, breast, lung and colorectal cancers and to be involved in the migration and invasion of cancer cells such as breast cancer cells and neuroblastomas (Miyoshi et al. 2010; Choi et al. 2011; Oh et al. 2011). Several studies have reported a relationship between TG2 expression and doxorubicin drug resistance but the mechanism has not been fully clarified. Here, the distribution of TG2 was studied in SK-n-BE(2) neuroblastoma cells after doxorubicin treatment (10 μM for 3 h). The immunoelectron microscopic localization showed that treatment with the anti-cancer drug doxorubicin induced a translocation of the enzyme to the cell surface at the level of plasma membrane projections (Fig. 8). Cell surface microvilli displayed numerous microvesicles on their inside; these appeared to be decorated with gold particles indicating the presence of TG2. These observations also provide further insights regarding the possible mechanism utilized by the cell to externalize TG2, suggesting that it is delivered to the surface inside small vesicles (Fig. 8a).Fig. 8

Bottom Line: Human tissue samples of myocardium and gut mucosa (diseased and healthy) are also analyzed.We describe a possible unrecognized location of TG2.Our findings thus provide useful insights regarding the functions and regulation of this pleiotropic enzyme.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, University of Rome 'Tor Vergata', Rome, Italy.

ABSTRACT
Transglutaminase type II (TG2) is a pleiotropic enzyme that exhibits various activities unrelated to its originally identified functions. Apart from post-translational modifications of proteins (peculiar to the transglutaminase family enzymes), TG2 is involved in diverse biological functions, including cell death, signaling, cytoskeleton rearrangements, displaying enzymatic activities, G-protein and non-enzymatic biological functions. It is involved in a variety of human diseases such as celiac disease, diabetes, neurodegenerative diseases, inflammatory disorders and cancer. Regulatory mechanisms might exist through which cells control multifunctional protein expression as a function of their sub-cellular localization. The definition of the tissue and cellular distribution of such proteins is important for the determination of their function(s). We investigate the sub-cellular localization of TG2 by confocal and immunoelectron microscopy techniques in order to gain an understanding of its properties. The culture conditions of human sarcoma cells (2fTGH cells), human embryonic kidney cells (HEK293(TG)) and human neuroblastoma cells (SK-n-BE(2)) are modulated to induce various stimuli. Human tissue samples of myocardium and gut mucosa (diseased and healthy) are also analyzed. Immuno-gold labeling indicates that TG2 is localized in the nucleus, mitochondria and endoplasmic reticulum under physiological conditions but that this is not a stable association, since different locations or different amounts of TG2 can be observed depending on stress stimuli or the state of activity of the cell. We describe a possible unrecognized location of TG2. Our findings thus provide useful insights regarding the functions and regulation of this pleiotropic enzyme.

Show MeSH
Related in: MedlinePlus