NUCLEAR LOCALIZATION OF ACTIVE MATRIX METALLOPROTEINASE-2 IN CIGARETTE SMOKE-EXPOSED APOPTOTIC ENDOTHELIAL CELLS

Autor:	Ruta, Aldonyte, Aldonyte, Ruta, Mark, Brantly, Brantly, Mark, Edward, Block, Block, Edward, Jawaharlal, Patel, Patel, Jawaharlal, Jianliang, Zhang, Zhang, Jianliang
Rok vydání:	2009
Předmět:	Pulmonary and Respiratory Medicine Programmed cell death Pathology medicine.medical_specialty Endothelium Swine Clinical Biochemistry Apoptosis Pulmonary Artery Matrix metalloproteinase Annexin Smoke medicine Animals Gelatinase Annexin A5 Molecular Biology Cells Cultured Cell Nucleus Metalloproteinase Chemistry Smoking Nuclear matrix Cell biology medicine.anatomical_structure Matrix Metalloproteinase 2 Endothelium Vascular Poly(ADP-ribose) Polymerases
Zdroj:	Experimental Lung Research. 35:59-75
ISSN:	1521-0499 0190-2148
DOI:	10.1080/01902140802406059
Popis:	Cigarette smoke (CS)-induced activation of proteases such as matrix metalloproteinases (MMPs) contributes to lung alveolar destruction due to cell death. The aim of this study was to determine whether MMPs are produced in pulmonary artery endothelial cells (PAECs) and whether CS activation of MMPs is associated with apoptosis. Cultured PAECs were exposed to CS and subjected to assessments of apoptosis and MMPs. Western blotting and in situ zymography were performed to localize gelatinolytic activity and to identify enzymes. CS-induced apoptosis, i.e., enhanced annexin V binding and cleaved poly-ADP-ribose-polymerase (PARP), correlated with increased degradation of gelatin, a substrate of MMPs. The levels of pro-MMP-2 and active MMP-2 were increased in cytosolic and nuclear fractions isolated from CS-exposed cells. MMP-2 protein colocalized with gelatinolytic activity in the nucleus of CS-exposed cells undergoing apoptosis. These observations support the notion that MMP-2 contributes to CS-induced gelatinase activity, which localizes in the nuclear region primarily and correlates with annexin V binding and PARP cleavage. This suggests a novel function of MMP-2 in the degradation of the nuclear matrix in CS-induced endothelial apoptosis.
Databáze:	OpenAIRE
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