TY - JOUR
T1 - Anti-CD3 activation of human CD4+ T cells increases expression of the intracellular β-endorphin endopeptidase (IDE/γ-EpGE)
AU - Sarada, Boppana
AU - Thiele, Dwain L
AU - Dang, Tuyet
AU - Lee, Jong
AU - Safavia, Afshin
AU - Hersh, Louis B.
AU - Cottam, Gene L.
PY - 1998/5/1
Y1 - 1998/5/1
N2 - In this study, increased expression of an endopeptidase hydrolyzing β- endorphin (β-Ep) to γ-endorphin (γ-Ep, β-Ep1-17) was observed upon immobilized anti-CD3 stimulated activation of human peripheral blood CD4+ T cells (hCD4+ T cells). Although freshly isolated hCD4+ T cells are devoid of significant β-Ep endopeptidase activity (< 0.1 nmol h-1 106 cells- 1), activation of these cells with immobilized anti-CD3 results in a time dependent appearance of β-Ep endopeptidase activity which reaches a maximal value of 17.4 ± 0.48 nmol h-1 106 cells-1 after 48 h of culture. Significant up-regulation of both mRNA encoding IDE/γ-EpGE and immunoreactive protein are observed in anti-CD3 stimulated hCD4+ T cells, indicating transcription and translation of IDE/γ-EpGE may be elevated. No significant hydrolysis of exogenous β-Ep is observed with intact hCD4+ T cells whether quiescent or activated or from preparations of hCD4+ T cell membranes. Therefore, this activity appears to be intracellular. Immunoreactive IDE/γ-EpGE is detected inside activated hCD4+ T cells. Analysis of metabolites generated upon hydrolysis of β-Ep with lysed activated hCD4+ T cell preparations identified the presence of: β-Ep1-18, β-Ep2-18, β-Ep1-17, β-Ep2-17, β-Ep18-31, β-Ep19-31, β-Ep1-13, β-Ep2- 13, β-Ep18-26, and β-Ep20-31 as major metabolites and the majority of these are consistent with β-Ep hydrolytic activity attributable to IDE/γ-EpGE.
AB - In this study, increased expression of an endopeptidase hydrolyzing β- endorphin (β-Ep) to γ-endorphin (γ-Ep, β-Ep1-17) was observed upon immobilized anti-CD3 stimulated activation of human peripheral blood CD4+ T cells (hCD4+ T cells). Although freshly isolated hCD4+ T cells are devoid of significant β-Ep endopeptidase activity (< 0.1 nmol h-1 106 cells- 1), activation of these cells with immobilized anti-CD3 results in a time dependent appearance of β-Ep endopeptidase activity which reaches a maximal value of 17.4 ± 0.48 nmol h-1 106 cells-1 after 48 h of culture. Significant up-regulation of both mRNA encoding IDE/γ-EpGE and immunoreactive protein are observed in anti-CD3 stimulated hCD4+ T cells, indicating transcription and translation of IDE/γ-EpGE may be elevated. No significant hydrolysis of exogenous β-Ep is observed with intact hCD4+ T cells whether quiescent or activated or from preparations of hCD4+ T cell membranes. Therefore, this activity appears to be intracellular. Immunoreactive IDE/γ-EpGE is detected inside activated hCD4+ T cells. Analysis of metabolites generated upon hydrolysis of β-Ep with lysed activated hCD4+ T cell preparations identified the presence of: β-Ep1-18, β-Ep2-18, β-Ep1-17, β-Ep2-17, β-Ep18-31, β-Ep19-31, β-Ep1-13, β-Ep2- 13, β-Ep18-26, and β-Ep20-31 as major metabolites and the majority of these are consistent with β-Ep hydrolytic activity attributable to IDE/γ-EpGE.
KW - HCD4 T cells
KW - Insulin degrading enzyme (IDE)
KW - β-Endorphin
KW - γ-Endorphin generating enzyme
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U2 - 10.1016/S0165-5728(97)00268-3
DO - 10.1016/S0165-5728(97)00268-3
M3 - Article
C2 - 9626998
AN - SCOPUS:0032078738
VL - 85
SP - 59
EP - 68
JO - Journal of Neuroimmunology
JF - Journal of Neuroimmunology
SN - 0165-5728
IS - 1
ER -