Role of High-Mobility Group Box 1 Protein and Poly(ADP-Ribose) Polymerase 1 Degradation inChlamydia trachomatis-Induced Cytopathicity
- 1 July 2010
- journal article
- Published by American Society for Microbiology in Infection and Immunity
- Vol. 78 (7), 3288-3297
- https://doi.org/10.1128/iai.01404-09
Abstract
As intracellular bacteria, chlamydiae block the apoptotic pathways of their host cells. However, the infection of epithelial cells causes the loss of cell membrane integrity and can result in nonapoptotic death. Normally, cells undergoing necrosis release high-mobility group box 1 protein (HMGB1) that acts as an important proinflammatory mediator. Here, we show that inChlamydia trachomatis-infected HeLa cells HMGB1 is not translocated from the nucleus to the cytosol and not released from injured cells in increased amounts. At 48 h after infection, degradation of HMGB1 was observed. In infected cells, poly(ADP-ribose) polymerase 1 (PARP-1), a DNA repair enzyme that also regulates HMGB1 translocation, was found to be cleaved into fragments that correspond to a necrosislike pattern of PARP-1 degradation. Cell-free cleavage assays and immunoprecipitation using purified proteolytic fractions from infected cells demonstrated that the chlamydial-protease-like activity factor (CPAF) is responsible for the cleavage of both HMGB1 and PARP-1. Proteolytic cleavage of PARP-1 was accompanied by a significant decrease in the enzymatic activity in a time-dependent manner. The loss of PARP-1 function obviously affects the viability ofChlamydia-infected cells because silencing of PARP-1 in uninfected HeLa cells with specific small interfering RNA results in increased cell membrane permeability. Our findings suggest that theChlamydia-specific protease CPAF interferes with necrotic cell death pathways. By the degradation of HMGB1 and PARP-1, the pathogen may have evolved a strategy to reduce the inflammatory response to membrane-damaged cellsin vivo.Keywords
This publication has 39 references indexed in Scilit:
- Classification of cell death: recommendations of the Nomenclature Committee on Cell Death 2009Cell Death & Differentiation, 2008
- Cytopathicity of Chlamydia is largely reproduced by expression of a single chlamydial proteaseThe Journal of cell biology, 2008
- Chlamydophila pneumoniae derived from inclusions late in the infectious cycle induce aponecrosis in human aortic endothelial cellsBMC Microbiology, 2008
- Mechanisms of host cell exit by the intracellular bacteriumChlamydiaProceedings of the National Academy of Sciences of the United States of America, 2007
- Activation of Poly(ADP)-ribose Polymerase (PARP-1) Induces Release of the Pro-inflammatory Mediator HMGB1 from the NucleusOnline Journal of Public Health Informatics, 2007
- Characterization of Host Cell Death Induced byChlamydia trachomatisInfection and Immunity, 2006
- Chlamydia and programmed cell deathCurrent Opinion in Microbiology, 2006
- Apoptosis, Pyroptosis, and Necrosis: Mechanistic Description of Dead and Dying Eukaryotic CellsInfection and Immunity, 2005
- Cell death, BAX activation, and HMGB1 release during infection with ChlamydiaMicrobes and Infection, 2004
- Role of Poly(ADP-ribose) Polymerase (PARP) Cleavage in ApoptosisOnline Journal of Public Health Informatics, 1999