Imbalance of mitochondrial-nuclear cross talk in isocyanate mediated pulmonary endothelial cell dysfunction
| Autor: | Smita Banerjee, Hariom Panwar, Neelam Pathak, Gorantla V. Raghuram, Saba Khan, Arpit Bhargava, Deepika Jain, Pradyumna Kumar Mishra |
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| Rok vydání: | 2012 |
| Předmět: |
Pulmonary toxicity
DNA damage Clinical Biochemistry Apoptosis Mitochondrion Biology Pulmonary Artery medicine.disease_cause Biochemistry Cell Line chemistry.chemical_compound medicine Humans Endothelial cell apoptosis lcsh:QH301-705.5 Environmental medicine Cell Nucleus lcsh:R5-920 Occupational health Organic Chemistry Endothelial Cells Mitochondrial oxidative stress Isocyanate Mitochondria Endothelial stem cell chemistry lcsh:Biology (General) Gene Expression Regulation Immunology Signal transduction lcsh:Medicine (General) Reactive Oxygen Species Oxidative stress DNA Damage Isocyanates Research Paper |
| Zdroj: | Redox Biology Redox Biology, Vol 1, Iss 1, Pp 163-171 (2013) |
| ISSN: | 2213-2317 |
| Popis: | Mechanistic investigations coupled with epidemiology, case-control, cohort and observational studies have increasingly linked isocyanate exposure (both chronic and acute) with pulmonary morbidity and mortality. Though ascribed for impairment in endothelial cell function, molecular mechanisms of these significant adverse pulmonary outcomes remains poorly understood. As preliminary studies conducted in past have failed to demonstrate a cause-effect relationship between isocyanate toxicity and compromised pulmonary endothelial cell function, we hypothesized that direct exposure to isocyanate may disrupt endothelial structural lining, resulting in cellular damage. Based on this premise, we comprehensively evaluated the molecular repercussions of methyl isocyanate (MIC) exposure on human pulmonary arterial endothelial cells (HPAE-26). We examined MIC-induced mitochondrial oxidative stress, pro-inflammatory cytokine response, oxidative DNA damage response and apoptotic index. Our results demonstrate that exposure to MIC, augment mitochondrial reactive oxygen species production, depletion in antioxidant defense enzymes, elevated pro-inflammatory cytokine response and induced endothelial cell apoptosis via affecting the balance of mitochondrial-nuclear cross talk. We herein delineate the first and direct molecular cascade of isocyanate-induced pulmonary endothelial cell dysfunction. The results of our study might portray a connective link between associated respiratory morbidities with isocyanate exposure, and indeed facilitate to discern the exposure-phenotype relationship in observed deficits of pulmonary endothelial cell function. Further, understanding of inter- and intra-cellular signaling pathways involved in isocyanate-induced endothelial damage would not only aid in biomarker identification but also provide potential new avenues to target specific therapeutic interventions. Graphical abstract Highlights ► Pulmonary endothelial cells accomplish a vast variety of specialized functions. ► A balance in mitochondrial-nuclear cross talk is essential for endothelial integrity. ► Methyl isocyanate impairs redox balance in endothelial milieu. ► We profess a corollary between respiratory morbidities and methyl isocyanate exposure. |
| Databáze: | OpenAIRE |
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