Transglutaminase overexpression sensitizes neuronal cell lines to apoptosis by increasing mitochondrial membrane potential and cellular oxidative stress

Mauro Piacentini, Maria Grazia Farrace, Lucia Piredda, Paola Matarrese, Fabiola Ciccosanti, Laura Falasca, Carlo Rodolfo, Anna Maria Giammarioli, Elisabetta Verderio, Martin Griffin, Walter Malorni

Research output: Contribution to journalArticle

Abstract

'Tissue' transglutaminase (tTG) selectively accumulates in cells undergoing apoptosis both in vivo and in vitro. Considering the central role played by mitochondria in apoptosis, we investigated the relationships existing amongst tTG expression, apoptosis and mitochondrial function. To this aim we studied the mechanisms of apoptosis in a neuronal cell line (SK-N-BE (2)) in which the tTG-expression was driven by a constitutive promoter. Furthermore, a tet-off inducible promoter was also used in 3T3 fibroblastic cells used as control. Both cell lines, when expressing tTG, appeared 'sensitized' to apoptosis. Strikingly, we found major differences in the morphological features of mitochondria among cell lines in the absence of apoptotic stimuli. In addition, these ultrastructural characteristics were associated with specific functional features: (i) constitutively hyperpolarized mitochondria and (ii) increased reactive oxygen intermediates production. Importantly, after mitochondrial-mediated apoptosis by staurosporine, a rapid loss of mitochondrial membrane potential was found in tTG cells only. Taken together, these results seem to suggest that, via hyperpolarization, tTG might act as a 'sensitizer' towards apoptotic stimuli specifically targeted to mitochondria. These results could also be of pathogenetic relevance for those diseases that are characterized by increased tTG and apoptotic rate together with impaired mitochondrial function, e.g. in some neurodegenerative disease.
Original languageEnglish
Pages (from-to)1061-1072
Number of pages12
JournalJournal of Neurochemistry
Volume81
Issue number5
Early online date21 May 2001
DOIs
Publication statusPublished - Jun 2002

Keywords

  • apoptosis
  • mitochondrial membrane potential
  • transglutaminase

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    Piacentini, M., Farrace, M. G., Piredda, L., Matarrese, P., Ciccosanti, F., Falasca, L., Rodolfo, C., Giammarioli, A. M., Verderio, E., Griffin, M., & Malorni, W. (2002). Transglutaminase overexpression sensitizes neuronal cell lines to apoptosis by increasing mitochondrial membrane potential and cellular oxidative stress. Journal of Neurochemistry, 81(5), 1061-1072. https://doi.org/10.1046/j.1471-4159.2002.00898.x