Thiol Redox Transitions in Cell Signaling: a Lesson from N-Acetylcysteine
The functional status of cells is under the control of external stimuli affecting the function of critical proteins and eventually gene expression. Signal sensing and transduction by messengers to specific effectors operate by post-translational modification of proteins, among which thiol redox swit...
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| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2010-01-01
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| Series: | The Scientific World Journal |
| Online Access: | http://dx.doi.org/10.1100/tsw.2010.104 |
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| author | Tiziana Parasassi Roberto Brunelli Graziella Costa Marco De Spirito Ewa Krasnowska Thomas Lundeberg Eugenia Pittaluga Fulvio Ursini |
| author_facet | Tiziana Parasassi Roberto Brunelli Graziella Costa Marco De Spirito Ewa Krasnowska Thomas Lundeberg Eugenia Pittaluga Fulvio Ursini |
| author_sort | Tiziana Parasassi |
| collection | DOAJ |
| description | The functional status of cells is under the control of external stimuli affecting the function of critical proteins and eventually gene expression. Signal sensing and transduction by messengers to specific effectors operate by post-translational modification of proteins, among which thiol redox switches play a fundamental role that is just beginning to be understood. The maintenance of the redox status is, indeed, crucial for cellular homeostasis and its dysregulation towards a more oxidized intracellular environment is associated with aberrant proliferation, ultimately related to diseases such as cancer, cardiovascular disease, and diabetes. Redox transitions occur in sensitive cysteine residues of regulatory proteins relevant to signaling, their evolution to metastable disulfides accounting for the functional redox switch. N-acetylcysteine (NAC) is a thiol-containing compound that is able to interfere with redox transitions of thiols and, thus, in principle, able to modulate redox signaling. We here review the redox chemistry of NAC, then screen possible mechanisms to explain the effects observed in NAC-treated normal and cancer cells; such effects involve a modification of global gene expression, thus of functions and morphology, with a leitmotif of a switch from proliferation to terminal differentiation. The regulation of thiol redox transitions in cell signaling is, therefore, proposed as a new tool, holding promise not only for a deeper explanation of mechanisms, but indeed for innovative pharmacological interventions. |
| format | Article |
| id | doaj-art-944fa85af19145398261cbd2ccb42a2e |
| institution | OA Journals |
| issn | 1537-744X |
| language | English |
| publishDate | 2010-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | The Scientific World Journal |
| spelling | doaj-art-944fa85af19145398261cbd2ccb42a2e2025-08-20T02:09:47ZengWileyThe Scientific World Journal1537-744X2010-01-01101192120210.1100/tsw.2010.104Thiol Redox Transitions in Cell Signaling: a Lesson from N-AcetylcysteineTiziana Parasassi0Roberto Brunelli1Graziella Costa2Marco De Spirito3Ewa Krasnowska4Thomas Lundeberg5Eugenia Pittaluga6Fulvio Ursini7Istituto di Neurobiologia e Medicina Molecolare, CNR, Roma, ItalyDipartimento di Ginecologia e Ostetricia, Università di Roma Sapienza, Roma, ItalyIstituto di Neurobiologia e Medicina Molecolare, CNR, Roma, ItalyIstituto di Fisica, Facoltà di Medicina, Università Cattolica del Sacro Cuore, Roma, ItalyIstituto di Neurobiologia e Medicina Molecolare, CNR, Roma, ItalyFAAB Sabbatsbergs Hospital, Stockholm, SwedenIstituto di Neurobiologia e Medicina Molecolare, CNR, Roma, ItalyDipartimento di Chimica Biologica, Università di Padova, Padova, ItalyThe functional status of cells is under the control of external stimuli affecting the function of critical proteins and eventually gene expression. Signal sensing and transduction by messengers to specific effectors operate by post-translational modification of proteins, among which thiol redox switches play a fundamental role that is just beginning to be understood. The maintenance of the redox status is, indeed, crucial for cellular homeostasis and its dysregulation towards a more oxidized intracellular environment is associated with aberrant proliferation, ultimately related to diseases such as cancer, cardiovascular disease, and diabetes. Redox transitions occur in sensitive cysteine residues of regulatory proteins relevant to signaling, their evolution to metastable disulfides accounting for the functional redox switch. N-acetylcysteine (NAC) is a thiol-containing compound that is able to interfere with redox transitions of thiols and, thus, in principle, able to modulate redox signaling. We here review the redox chemistry of NAC, then screen possible mechanisms to explain the effects observed in NAC-treated normal and cancer cells; such effects involve a modification of global gene expression, thus of functions and morphology, with a leitmotif of a switch from proliferation to terminal differentiation. The regulation of thiol redox transitions in cell signaling is, therefore, proposed as a new tool, holding promise not only for a deeper explanation of mechanisms, but indeed for innovative pharmacological interventions.http://dx.doi.org/10.1100/tsw.2010.104 |
| spellingShingle | Tiziana Parasassi Roberto Brunelli Graziella Costa Marco De Spirito Ewa Krasnowska Thomas Lundeberg Eugenia Pittaluga Fulvio Ursini Thiol Redox Transitions in Cell Signaling: a Lesson from N-Acetylcysteine The Scientific World Journal |
| title | Thiol Redox Transitions in Cell Signaling: a Lesson from N-Acetylcysteine |
| title_full | Thiol Redox Transitions in Cell Signaling: a Lesson from N-Acetylcysteine |
| title_fullStr | Thiol Redox Transitions in Cell Signaling: a Lesson from N-Acetylcysteine |
| title_full_unstemmed | Thiol Redox Transitions in Cell Signaling: a Lesson from N-Acetylcysteine |
| title_short | Thiol Redox Transitions in Cell Signaling: a Lesson from N-Acetylcysteine |
| title_sort | thiol redox transitions in cell signaling a lesson from n acetylcysteine |
| url | http://dx.doi.org/10.1100/tsw.2010.104 |
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