International journal of radiation oncology, biology, physics, 2012-04, Vol.82 (5), p.1559-1566
2012
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- Autor(en) / Beteiligte
- Titel
- Irradiation Alters MMP-2/TIMP-2 System and Collagen Type IV Degradation in Brain
- Ist Teil von
- International journal of radiation oncology, biology, physics, 2012-04, Vol.82 (5), p.1559-1566
- Ort / Verlag
- New York, NY: Elsevier Inc
- Erscheinungsjahr
- 2012
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Purpose Blood-brain barrier (BBB) disruption is one of the major consequences of radiation-induced normal tissue injury in the central nervous system. We examined the effects of whole-brain irradiation on matrix metalloproteinases (MMPs)/tissue inhibitors of metalloproteinases (TIMPs) and extracellular matrix (ECM) degradation in the brain. Methods and Materials Animals received either whole-brain irradiation (a single dose of 10 Gy γ-rays or a fractionated dose of 40 Gy γ-rays, total) or sham-irradiation and were maintained for 4, 8, and 24 h following irradiation. mRNA expression levels of MMPs and TIMPs in the brain were analyzed by real-time reverse transcriptase-polymerase chain reaction (PCR). The functional activity of MMPs was measured by in situ zymography, and degradation of ECM was visualized by collagen type IV immunofluorescent staining. Results A significant increase in mRNA expression levels of MMP-2, MMP-9, and TIMP-1 was observed in irradiated brains compared to that in sham-irradiated controls. In situ zymography revealed a strong gelatinolytic activity in the brain 24 h postirradiation, and the enhanced gelatinolytic activity mediated by irradiation was significantly attenuated in the presence of anti-MMP-2 antibody. A significant reduction in collagen type IV immunoreactivity was also detected in the brain at 24 h after irradiation. In contrast, the levels of collagen type IV were not significantly changed at 4 and 8 h after irradiation compared with the sham-irradiated controls. Conclusions The present study demonstrates for the first time that radiation induces an imbalance between MMP-2 and TIMP-2 levels and suggests that degradation of collagen type IV, a major ECM component of BBB basement membrane, may have a role in the pathogenesis of brain injury.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0360-3016eISSN: 1879-355XDOI: 10.1016/j.ijrobp.2010.12.032Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3309226
- Format
- –
- Schlagworte
- Animals, ANTIBODIES, Basement membranes, Biological and medical sciences, Biological effects of radiation, BLOOD-BRAIN BARRIER, BRAIN, Brain - metabolism, Brain - radiation effects, Central nervous system, Cerebral Cortex - metabolism, Cerebral Cortex - radiation effects, COLLAGEN, Collagen type IV, Collagen Type IV - genetics, Collagen Type IV - metabolism, Collagen Type IV - radiation effects, Cranial Irradiation - adverse effects, Cranial Irradiation - methods, Extracellular matrix, Extracellular Matrix - metabolism, Extracellular Matrix - radiation effects, Female, Fluorescent Antibody Technique - methods, Fundamental and applied biological sciences. Psychology, gamma Radiation, Gelatinase A, Gelatinase B, Gelatinases - metabolism, Gelatinases - radiation effects, Gene expression, Hematology, Oncology and Palliative Medicine, Hippocampus - metabolism, Hippocampus - radiation effects, Immunoreactivity, Injuries, Ionizing radiations, IRRADIATION, Male, Matrix metalloproteinase, Matrix Metalloproteinase 2 - genetics, Matrix Metalloproteinase 2 - metabolism, Matrix Metalloproteinase 2 - radiation effects, Matrix Metalloproteinase 9 - genetics, Matrix Metalloproteinase 9 - metabolism, Matrix Metalloproteinase 9 - radiation effects, Matrix metalloproteinases, Medical sciences, MEMBRANES, MESSENGER-RNA, Mice, Mice, Inbred C57BL, PATHOGENESIS, POLYMERASE CHAIN REACTION, Radiation, RADIATION DOSES, RADIATION INJURIES, Radiation Injuries, Experimental - etiology, Radiation Injuries, Experimental - metabolism, Radiation therapy and radiosensitizing agent, Radiology, RADIOLOGY AND NUCLEAR MEDICINE, Rats, Rats, Inbred F344, Real-Time Polymerase Chain Reaction, RNA, Messenger - metabolism, Time Factors, Tissue inhibitor of metalloproteinase 1, Tissue inhibitor of metalloproteinase 2, Tissue Inhibitor of Metalloproteinase-2 - genetics, Tissue Inhibitor of Metalloproteinase-2 - metabolism, Tissue Inhibitor of Metalloproteinase-2 - radiation effects, Tissue inhibitor of metalloproteinases, Tissues, organs and organisms biophysics, Treatment with physical agents, Treatment. General aspects, Tumors, Whole-brain irradiation