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Transglutaminase overexpression sensitizes neuronal cell lines to apoptosis by increasing mitochondrial membrane potential and cellular oxidative stress
Author(s) -
Grazia Farrace Maria,
Piredda Lucia,
Matarrese Paola,
Ciccosanti Fabiola,
Falasca Laura,
Rodolfo Carlo,
Giammarioli Anna Maria,
Verderio Elisabetta,
Griffin Martin,
Malorni Walter
Publication year - 2002
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2002.00898.x
Subject(s) - mitochondrion , apoptosis , staurosporine , microbiology and biotechnology , biology , membrane potential , tissue transglutaminase , mitochondrial apoptosis induced channel , cell culture , oxidative stress , reactive oxygen species , inner mitochondrial membrane , signal transduction , biochemistry , protein kinase c , genetics , enzyme
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 stauro‐ sporine, 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.