Actin Is the Naturally Occurring Inhibitor of Deoxyribonuclease I

Lazarides, Elias; Lindberg, Uno

doi:10.1073/pnas.71.12.4742

Cited by 571 publications

(273 citation statements)

References 36 publications

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“…Two alternative possibilities for the acceleration of the DNase I activity by C1q can therefore be hypothesized. Either, in analogy to SAP (23), C1q may increase the access of DNase to the DNA in the chromatin of necrotic cells by displacing the DNA binding proteins, or C1q may block the immobilization of DNase by components of the actin cytoskeleton (59)(60)(61) and, as a consequence, increase the access of DNase to the chromatin.…”

Section: Discussionmentioning

confidence: 99%

Cooperation between C1q and DNase I in the clearance of necrotic cell–derived chromatin

Gaipl¹,

Beyer²,

Heyder³

et al. 2004

Arthritis & Rheumatism

105

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Objective. The efficient uptake of dying cells by phagocytes is essential to the avoidance of chronic inflammation. Some human autoimmune responses are thought to be driven by autoantigens from apoptotic or necrotic cells. We analyzed the role of C1q and DNase I in the disposal of necrotic cell-derived chromatin because deficiencies in these serum factors predispose to the development of systemic autoimmune disorders, such as systemic lupus erythematosus.Methods. Human necrotic peripheral blood lymphocytes were incubated in cell culture medium supplemented with various sera or serum components. Chromatin degradation was monitored by measuring the residual DNA content by flow cytometry. The uptake of necrotic cell-derived nuclei was analyzed by in vitro phagocytosis assays.Results. Reconstitution of C1q-depleted serum with C1q strongly increased its ability to degrade necrotic cell-derived chromatin. Although C1q itself displayed no DNase activity, it strongly augmented the activity of serum DNase I. Whereas an excess of recombinant DNase I degraded chromatin in the absence of C1q, efficient uptake of the predigested material by monocyte-derived phagocytes required the presence of C1q. These data show that C1q and DNase I cooperate in the degradation of chromatin from necrotic cells. Furthermore, C1q was found to be necessary for effective uptake of degraded chromatin by monocyte-derived phagocytes.Conclusion. C1q or DNase I deficiencies may precipitate autoimmunity in humans by a mechanism similar to that of other molecules that are involved in the safe, efficient, and rapid disposal of dying cells.

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Section: Discussionmentioning

confidence: 99%

Cooperation between C1q and DNase I in the clearance of necrotic cell–derived chromatin

Gaipl¹,

Beyer²,

Heyder³

et al. 2004

Arthritis & Rheumatism

105

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“…After washing the light membrane free of sucrose with twice-distilled water, proteins were extracted with EDTA according to Marchesi et al [8]. The extract was lyophilized and the protein purified on a column of DNase-agarose according to the method of Lazarides and Lindberg [5]. Parallely membrane proteins were extracted with EDTA from the membrane fraction obtained as above [7] but from livers of rats poisoned [3H] desmethylphalloin [9] (2 mg per kg, spec.…”

Section: Methodsmentioning

confidence: 99%

“…Although these properties strongly point to an actinlike nature, it was desirable to isolate and to characterize the liver filaments by additional comparing experiments. A characteristic property of actin recently described is its inhibitory effect on DNase-I [5], which can be counteracted by phalloidin [6]. We have now isolated a protein from cytoplasma membranes of rat liver by affinity chromatography on DNase-agarose [5] and identified it with muscle actin by gel electrophoresis and by its property to inhibit DNase-I by concentrations comparable with those of muscle actin.…”

Section: Introductionmentioning

confidence: 99%

“…A characteristic property of actin recently described is its inhibitory effect on DNase-I [5], which can be counteracted by phalloidin [6]. We have now isolated a protein from cytoplasma membranes of rat liver by affinity chromatography on DNase-agarose [5] and identified it with muscle actin by gel electrophoresis and by its property to inhibit DNase-I by concentrations comparable with those of muscle actin. Furthermore the phalloidin containing filaments from livers of poisoned rats were isolated by gel chromatography and identified as actin like filaments by electron microscopy.…”

Section: Introductionmentioning

confidence: 99%

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Isolation and identification of an actin from rat liver

Govindan¹,

Wieland²

1975

FEBS Letters

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“…Although not widely recognised as an ABP, Lazarides and Lindberg [13] were the first to suggest that DNase I may be a cytoskeletal protein.…”

Section: Introductionmentioning

confidence: 99%

The distribution of cofilin and DNase I in vivo

2002

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Actin is the principal component of the cytoskeleton, a structure that can be disassembled and reassembled in a matter of seconds in vivo. The state of assembly of actin in vivo is primarily regulated by one or more actin binding proteins (ABPs). Typically, the actions of ABPs have been studied one by one, however, we propose that multiple ABPs, acting cooperatively, may be involved in the control of actin filament length. Cofilin and DNase I are two ABPs that have previously been demonstrated to form a ternary complex with actin in vitro. This is the first report to demonstrate their co-localisation in vivo, and differences in their distributions. Our observations strongly suggest a physiological role for higher order complexes of actin in regulation of cytoskeletal assembly during processes such as cell division.

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Actin Is the Naturally Occurring Inhibitor of Deoxyribonuclease I

Cited by 571 publications

References 36 publications

Cooperation between C1q and DNase I in the clearance of necrotic cell–derived chromatin

Cooperation between C1q and DNase I in the clearance of necrotic cell–derived chromatin

Isolation and identification of an actin from rat liver

The distribution of cofilin and DNase I in vivo

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