TY - JOUR
T1 - Differential activation of a calcium-dependent endonuclease in human B lymphocytes - Role in ionomycin-induced apoptosis
AU - Aagaard-Tillery, Kjersti M.
AU - Jelinek, Diane F.
PY - 1995
Y1 - 1995
N2 - The state of B cell maturation profoundly influences the outcome, i.e., activation, growth arrest, or programmed cell death, of a variety of stimuli, including the calcium ionophore, ionomycin. Initial studies confirmed the observation that cell lines representative of immature B cells, i.e., Burkitt lymphoma cell lines, were induced to undergo apoptosis in response to ionomycin, whereas more mature B cell lines did not, and instead underwent cell cycle arrest in the G1 interval. To understand this differential outcome, we have focused on comparing the expression and activation of an endonuclease(s) in cells induced by ionomycin to undergo programmed cell death (Ramos) with cells resistant to ionomycin-induced programmed cell death (Ly1). Our results demonstrated that a low m.w. fraction of an endogenous Ca2+/Mg2+-dependent endonuclease was activated in Ramos cells, but not in activated Ly1 cells, following the addition of ionomycin. Of interest, however, low m.w. endogenous endonuclease(s) activity was induced when isolated Ly1 cell nuclei were treated with exogenous calcium instead. Use of field inversion gel electrophoresis further indicated that cleavage of DNA into large m.w. (>50 kbp) DNA fragments does not precede ionomycin-induced internucleosomal cleavage in Ramos cells or in ionomycin-resistant Ly1 cells. In summary, these data support the conclusion that ionomycin-induced apoptosis involves the activation of a latent, low m.w., calcium-responsive endonuclease and suggest that control of endonuclease derepression may contribute to cell-specific regulation of calcium ionophore-induced apoptosis.
AB - The state of B cell maturation profoundly influences the outcome, i.e., activation, growth arrest, or programmed cell death, of a variety of stimuli, including the calcium ionophore, ionomycin. Initial studies confirmed the observation that cell lines representative of immature B cells, i.e., Burkitt lymphoma cell lines, were induced to undergo apoptosis in response to ionomycin, whereas more mature B cell lines did not, and instead underwent cell cycle arrest in the G1 interval. To understand this differential outcome, we have focused on comparing the expression and activation of an endonuclease(s) in cells induced by ionomycin to undergo programmed cell death (Ramos) with cells resistant to ionomycin-induced programmed cell death (Ly1). Our results demonstrated that a low m.w. fraction of an endogenous Ca2+/Mg2+-dependent endonuclease was activated in Ramos cells, but not in activated Ly1 cells, following the addition of ionomycin. Of interest, however, low m.w. endogenous endonuclease(s) activity was induced when isolated Ly1 cell nuclei were treated with exogenous calcium instead. Use of field inversion gel electrophoresis further indicated that cleavage of DNA into large m.w. (>50 kbp) DNA fragments does not precede ionomycin-induced internucleosomal cleavage in Ramos cells or in ionomycin-resistant Ly1 cells. In summary, these data support the conclusion that ionomycin-induced apoptosis involves the activation of a latent, low m.w., calcium-responsive endonuclease and suggest that control of endonuclease derepression may contribute to cell-specific regulation of calcium ionophore-induced apoptosis.
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M3 - Article
C2 - 7561022
AN - SCOPUS:0029156724
SN - 0022-1767
VL - 155
SP - 3297
EP - 3307
JO - Journal of Immunology
JF - Journal of Immunology
IS - 7
ER -