ACTIVATION OF HUMAN MONOCYTE-DERIVED MACROPHAGES BY INTERFERON-GAMMA IS ACCOMPANIED BY INCREASE OF POLY(ADP-RIBOSE) POLYMERASE-ACTIVITY

被引：25

作者：

BERTON, G ^{[1
]}

SORIO, C ^{[1
]}

LAUDANNA, C ^{[1
]}

MENEGAZZI, M ^{[1
]}

DEPRATI, AC ^{[1
]}

SUZUKI, H ^{[1
]}

机构：

[1] UNIV VERONA,INST BIOL CHEM,I-37100 VERONA,ITALY

来源：

BIOCHIMICA ET BIOPHYSICA ACTA | 1991年 / 1091卷 / 01期

关键词：

INTERFERON-GAMMA; POLY(ADP-RIBOSYLATION); MACROPHAGE ACTIVATION; DNA STRAND BREAK;

D O I：

10.1016/0167-4889(91)90228-P

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

We have investigated poly(ADP-ribosyl)ation processes in human monocyte-derived macrophages and the effect of the activating cytokine, interferon gamma (IFN-gamma) on these processes. IFN-gamma was shown to increase the activity of poly(ADP-ribose) polymerase in human macrophages. A 2-3-fold enhancement of poly(ADP-ribose) polymerase activity was observed after 3-4 h of incubation with IFN-gamma, whose effects were dose-dependent and maximal at 20-50 U/ml. Staining with anti-poly(ADP-ribose) antibodies and purification of ADP-ribosylated nuclear proteins by affinity chromatography over boronate agarose showed that enhancement of poly(ADP-ribose) polymerase activity by IFN-gamma was accompanied by accumulation of poly(ADP-ribose) polymers in nuclear proteins. The effects of IFN-gamma on poly(ADP-ribose) polymerase activity were not due to an enhanced accumulation of the message for the enzyme, indicating that the activation of the enzyme activity was due to post-transcriptional modifications. IFN-gamma was shown to induce DNA strand breaks in human macrophages. This phenomenon followed the same time-course and was evident with the same doses of IFN-gamma that increased poly(ADP-ribose) polymerase activity. Since poly(ADP-ribose) polymerase is known to require DNA nicks for its activity, the capability of IFN-gamma to induce DNA strand breaks can explain its effects on poly(ADP-ribosyl)ation processes.

引用

页码：101 / 109

页数：9

共 48 条

[1]

ADAMIETZ P, 1984, METHOD ENZYMOL, V106, P462

[2]

AGARWAL S, 1988, J IMMUNOL, V140, P4187

[3]

Althaus F R, 1987, Mol Biol Biochem Biophys, V37, P1

[4]

ALTHAUS FR, 1982, J BIOL CHEM, V257, P5528