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Cysteine Proteases in Differentiation of Embryonic Stem Cells into Neural Cells

Azevedo-Pereira, Ricardo Luiz de ; Lima, Ana Paula C.A. ; Rodrigues, Deivid de Carvalho ; Rondinelli, Edson ; Medei, Emiliano Horácio ; Goldenberg, Regina Coeli ; Campos de Carvalho, Antonio Carlos ; Mendez-Otero, Rosalia

Stem cells and development, 2011-11, Vol.20 (11), p.1859-1872 [Periódico revisado por pares]

United States: Mary Ann Liebert, Inc

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Cysteine Proteases in Differentiation of Embryonic Stem Cells into Neural Cells
Autor: Azevedo-Pereira, Ricardo Luiz de ; Lima, Ana Paula C.A. ; Rodrigues, Deivid de Carvalho ; Rondinelli, Edson ; Medei, Emiliano Horácio ; Goldenberg, Regina Coeli ; Campos de Carvalho, Antonio Carlos ; Mendez-Otero, Rosalia
Assuntos: Animals ; Antigens, Differentiation - genetics ; Antigens, Differentiation - metabolism ; Calpain - antagonists & inhibitors ; Cathepsin L - antagonists & inhibitors ; Cathepsin L - metabolism ; Cell Differentiation ; Cell Line ; Cell Surface Extensions - metabolism ; Coculture Techniques ; Cystatin C - metabolism ; Cystatin C - pharmacology ; Cystatin C - physiology ; Cysteine Proteinase Inhibitors - pharmacology ; Embryoid Bodies - cytology ; Embryoid Bodies - drug effects ; Embryoid Bodies - enzymology ; Embryonic stem cells ; Embryonic Stem Cells - drug effects ; Embryonic Stem Cells - enzymology ; Embryonic Stem Cells - physiology ; Eye Proteins - metabolism ; GAP-43 Protein - genetics ; GAP-43 Protein - metabolism ; Gene Expression ; Homeodomain Proteins - metabolism ; Humans ; Intermediate Filament Proteins - genetics ; Intermediate Filament Proteins - metabolism ; Leucine - analogs & derivatives ; Leucine - pharmacology ; Membrane Potentials ; Mice ; Nerve Tissue Proteins - genetics ; Nerve Tissue Proteins - metabolism ; Nestin ; Neurofilament Proteins - metabolism ; Neurons ; Neurons - drug effects ; Neurons - enzymology ; Nuclear Proteins - genetics ; Nuclear Proteins - metabolism ; Original Research Reports ; Paired Box Transcription Factors - metabolism ; PAX6 Transcription Factor ; Physiological aspects ; Proteases ; Repressor Proteins - metabolism
É parte de: Stem cells and development, 2011-11, Vol.20 (11), p.1859-1872
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Descrição: Glycosylated mouse cystatin C (mCysC), an endogenous inhibitor of cysteine cathepsin proteases (CP), has been suggested as a cofactor of β-FGF to induce the differentiation of mouse embryonic stem cells into neural progenitor cells (NPCs). To investigate the possible role of CP in neural differentiation, we treated embryoid bodies (EBs) with (i) E64, an inhibitor of papain-like CP and of calpains, (ii) an inhibitor of cathepsin L (iCatL), (iii) an inhibitor of calpains (iCalp), or (iv) cystatins, and their ability to differentiate into neural cells was assessed. We show that the inhibition of CP induces a significant increase in Pax6 expression in EBs, leading to an increase in the number of nestin-positive cells after 3 days. Fourteen days after E64 treatment, we observed increased numbers of β-III-tubulin-positive cells, showing greater percentage of immature neurons, and this feature persisted up to 24 days. At this point, we encountered higher numbers of neurons with inward Na + current compared with untreated EBs. Further, we show that mCysC and iCatL, but not unglycosylated egg white cystatin or iCalp, increased the numbers of NPCs. In contrast to E64 and iCatL, mCysC did not inhibit CP in EBs and its neural-inducing activity required β-FGF. We propose that the inhibition of CP induces the differentiation of mouse embryonic stem cells into NPCs and neurons through a mechanism that is distinct from CysC-induced neural differentiation.
Editor: United States: Mary Ann Liebert, Inc
Idioma: Inglês

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Cysteine Proteases in Differentiation of Embryonic Stem Cells into Neural Cells

Azevedo-Pereira, Ricardo Luiz de ; Lima, Ana Paula C.A. ; Rodrigues, Deivid de Carvalho ; Rondinelli, Edson ; Medei, Emiliano Horácio ; Goldenberg, Regina Coeli ; Campos de Carvalho, Antonio Carlos ; Mendez-Otero, Rosalia

United States: Mary Ann Liebert, Inc

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