QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, June 1, 2003, 23(11):4635-4644

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (13) Citing Articles via Google Scholar Google Scholar Articles by Pasquini, L. A. Articles by Soto, E. F. Search for Related Content PubMed PubMed Citation Articles by Pasquini, L. A. Articles by Soto, E. F.

 Previous Article  |  Next Article 

Inhibition of the Proteasome by Lactacystin Enhances Oligodendroglial Cell Differentiation

Laura A. Pasquini, Pablo M. Paez, Marcos A. N. Besio Moreno, Juana M. Pasquini, and Eduardo F. Soto

Departamento de Química Biológica, Instituto de Química y Fisicoquímica Biológica, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires 1113, Argentina

We have used lactacystin, a specific inhibitor of the 26S proteasome, in oligodendroglial cell (OLGc) primary cultures to explore the possible participation of the proteasome–ubiquitin-dependent pathway in the decision of the OLGcs to arrest their proliferation and start differentiation. Addition of lactacystin at various concentrations to cultures containing a majority of OLGc was found to produce their withdrawal from the cell cycle and to induce their biochemical and morphological differentiation, with the appearance of extensive myelin-like sheets. The three classic proteolytic activities of the proteasome were significantly decreased in the lactacystin-treated cultures, and the immunocytochemical analysis showed an increase in the number of O4-, O1-, myelin basic protein-, and myelin proteolipid protein-positive cells and a decrease in A2B5-reacting cells. Quantitative immunochemical evaluation of the expression of certain proteins controlling the cell cycle showed an increase in p27^kip1-, cyclin D-, and cdk4-positive cells, with a decrease in cyclin E- and cdk2-positive cells. In the lactacystin-treated OLGcs, there was a dose-dependent decrease in the number of cells incorporating bromodeoxyuridine and in the activity of the complexes cyclin D–cdk4 and cyclin E–cdk2. Furthermore, increased levels of expression of several STAT factors were found, suggesting that proteasome inhibition in OLGcs could stabilize signals of survival and differentiation that might be processed through the JAK/STAT signaling cascade.

Key words: oligodendroglial cells; lactacystin; MG132; differentiation; cyclins; p27^kip1; JAK/STAT; ubiquitin; proteasome; myelination

---

Received Aug. 26, 2002; revised Mar. 12, 2003; accepted Mar. 19, 2003.

This article has been cited by other articles:

				F. Guo, J. Ma, E. McCauley, P. Bannerman, and D. Pleasure Early Postnatal Proteolipid Promoter-Expressing Progenitors Produce Multilineage Cells In Vivo J. Neurosci., June 3, 2009; 29(22): 7256 - 7270. [Abstract] [Full Text] [PDF]

				M. Fujita, S. Sugama, M. Nakai, T. Takenouchi, J. Wei, T. Urano, S. Inoue, and M. Hashimoto {alpha}-Synuclein Stimulates Differentiation of Osteosarcoma Cells: RELEVANCE TO DOWN-REGULATION OF PROTEASOME ACTIVITY J. Biol. Chem., February 23, 2007; 282(8): 5736 - 5748. [Abstract] [Full Text] [PDF]

				W. Guo, F. Shang, Q. Liu, L. Urim, M. Zhang, and A. Taylor Ubiquitin-proteasome pathway function is required for lens cell proliferation and differentiation. Invest. Ophthalmol. Vis. Sci., June 1, 2006; 47(6): 2569 - 2575. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help