Molecular Cloning of the cDNA Encoding Human Deoxyribonuclease II

Yasuda, Toshihiro; Takeshita, Hitoshi; Iida, Reiko; Nakajima, Tamiko; Hosomi, Osamu; Nakashima, Y.; Kishi, Koichiro

doi:10.1074/jbc.273.5.2610

Cited by 81 publications

(55 citation statements)

References 42 publications

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“…An assay of in vitro apoptosis indicates that anti-DNase II antibody can prevent DNA fragmentation in a nuclear extract cell-free system in pH4 and DNase II is the main DNase concerning radiationinduced apoptosis in HL60 cells. Therefore in our study, the most likely candidate for the acid DNase in lysosomes that causes DNA fragmentation is DNase II (12,23,24). However, it is unlikely that the action of DNase II directly generates TUNEL-positive cells, because cleavage of DNA by DNase II generates 5?-hydroxyl and 3?-phosphate ends that cannot be used as substrates for terminal transferase.…”

Section: Discussionmentioning

confidence: 99%

Nuclear Translocation of DNase II and Acid Phosphatase during Radiation-induced Apoptosis in HL60 Cells

et al. 2003

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DNase II is involved in DNA fragmentation induced by a variety of treatments. However, according to past reports DNase II does not directly generate TUNEL (in situ DNA end labeling)-positive cells. The purpose of this study was to investigate the participation of acid phosphatase in the generation of TUNEL-positive cells. DNase II-like proteins, whose molecular weights were 32-kDa, were detected in nuclear extracts of HL60 human myeloid leukemia cells post g-irradiation by SDS-PAGE and immunohistochemistry. Acidic nuclease activity was especially active in 32-kDa bands. TUNEL assay was positive post g-irradiation. From measurements of the activity of acid phosphatase, the activity in nuclear extracts increased remarkably post g-irradiation. g-irradiation can directly or indirectly activate DNase II. Once DNase II and acid phosphatase have been translocated from lysosomes into the nuclei, DNase II generates TUNEL reactive ends in combination with acid phosphatase.

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Section: Discussionmentioning

confidence: 99%

Nuclear Translocation of DNase II and Acid Phosphatase during Radiation-induced Apoptosis in HL60 Cells

et al. 2003

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“…The acidic nuclease, detected in HL-60 cells upon activation by U(V)C irradiation, is represented by four polypeptides of apparent molecular weight (M r ) 56, 48, 45 and 40 kDa, as revealed by SDS ± PAGE (Figure 1). The intensity of bands, which 40 we postulate that the nuclease monitored here represents a novel enzyme. It has been shown that in HL-60 cells an acidic nuclease but not a Ca 2+ /Mg 2+ -dependent nuclease is associated with the majority of the nucleolytic activity.…”

Section: Resultsmentioning

confidence: 99%

Activation of a low pH-dependent nuclease by apoptotic agents

Famulski

Macdonald²,

Paterson

et al. 1999

Cell Death Differ

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Intracellular acidification caused by agents such as UV(C), etoposide or ceramide accompanies the progression of apoptosis. It is suggested that cellular acidosis may set favorable conditions for a dormant, low pH-dependent (acidic) nuclease, which could be involved in intranucleosomal genome degradation, a hallmark of programmed cell death. Here we show that exposure of HL-60 cells to acidotic/ apoptotic agents results in the several-fold activation of a novel low pH-dependent (acidic) nuclease activity, as revealed by zymography. Its activity, which resides in nuclei, is associated with four polypeptides with apparent M r of 56, 48, 45 and 40 kDa. Treatment of HeLa cells with UV(C) or ceramide causes also the up-regulation of an acidic nuclease activity which is represented by 70 and 62 kDa polypeptides. These observations suggest that acidic nuclease activation can be induced by the same apoptotic agents in different cell types. In HL-60 cells, acidic nuclease up-regulation triggered by acidotic agents follows the induction of AP-1 transcription factor active complexes and accompanies the progression of apoptosis. Inhibition of AP-1 factor activity caused by either anti-caspase/anti-acidotic agent Zn 2+ or curcumin, an inhibitor of AP-1 binding to DNA and c-jun synthesis, protects cells from genome destruction. Acidic nuclease activation, however, is only partially inhibited by these factors. We propose that (i) the up-regulation of an acidic nuclease activity is governed by a regulatory pathway different from that responsible for AP-1 factor induction, caspases activation and intracellular acidification, and (ii) activation of an acidic nuclease does not cause any deleterious effects when AP-1 transcription factor induction, caspases activation and intracellular acidification are down-regulated. Thus, the acidic nuclease up-regulation alone is not a sufficient prerequisite for apoptosis.

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“…The anti-protease activity of LEI is lost during its conversion to active DNase II. As this DNase II is different from other DNases II already described, 25,26 and it is derived from LEI, we named it L-DNase II and we have demonstrated its involvement during apoptosis. 27 The aim of this study was to compare different morphological and biochemical parameters of apoptosis, including DNase activation in cells driven to apoptosis by different stimuli.…”

Section: Introductionmentioning

confidence: 99%

Differential involvement of DNases in HeLa cell apoptosis induced by etoposide and long term-culture

et al. 1999

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We have applied to human HeLa cells two different stimuli of apoptosis: the antitumoral drug etoposide, and a morè physiological' death condition, obtained by growing cells in the same medium for long time periods, for up to 10 days. Analysis of different parameters demonstrated that in both experimental systems the same apoptotic features are visible. However, the DNA degradation pattern appeared to be different, suggesting the involvement of different DNases. In this view, we have analyzed the activity and expression of Ca 2+ -Mg 2+ -dependent and acid DNases. We have observed that DNase I is not modulated during apoptosis. In contrast, the acid L-DNase II (derived from Leukocyte Elastase Inhibitor by post-translational modification), recently identified in our laboratory, is mainly active in the apoptotic pathway induced by long term-culture. Furthermore, we have provided evidence that while caspase 3 is activated by both inducers, caspase 1 is essential only for the etoposide-induced apoptosis.

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Molecular Cloning of the cDNA Encoding Human Deoxyribonuclease II

Cited by 81 publications

References 42 publications

Nuclear Translocation of DNase II and Acid Phosphatase during Radiation-induced Apoptosis in HL60 Cells

Nuclear Translocation of DNase II and Acid Phosphatase during Radiation-induced Apoptosis in HL60 Cells

Activation of a low pH-dependent nuclease by apoptotic agents

Differential involvement of DNases in HeLa cell apoptosis induced by etoposide and long term-culture

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