Journal
PROTEOMICS
Volume 7, Issue 21, Pages 3906-3918Publisher
WILEY
DOI: 10.1002/pmic.200700377
Keywords
antioxidant; diesel exhaust particle; difference gel electrophoresis; human bronchial epithelial cells; oxidative stress
Funding
- NIAID NIH HHS [U19 AI070453] Funding Source: Medline
- NIEHS NIH HHS [R01 ES012053, R01 ES013432] Funding Source: Medline
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Ambient particulate matter (PM) induces adverse health effects through the ability of pro-oxidative chemicals to induce the production of oxygen radicals and oxidant injury. Utilizing a proteomics strategy involving 2-D DIGE, immunoblotting, and real-time PCR, we demonstrate that organic diesel exhaust particle (DEP) chemicals induce an unfolding protein response (UPR.) and proinflammatory effects in the human bronchial epithelial cell line, BEAS-2B. DIGE and M S showed the induction of at least 14 proteins, among which heat shock protein 70 (HSP70), HSP40,TPR2, and T-complex protein 1 (zeta-subunit) are known to play a role in the UPR. Demonstrating increased HSP70 mRNA expression and nuclear translocation of HSF1, the key transcription factor responsible for HSP expression, further strengthened this notion. Immunoblotting demonstrated increased expression of ATF4, an ER stress-associated transcriptional enhancer responsible for differential protein translation under conditions of ER stress. Finally, the DEP extract induced the expression of IL-6 and IL-8 in the culture supernatant. The role of oxidative stress was demonstrated further by response subtraction in the presence of the thiol antioxidant, N-acetyl cysteine. Our data suggest that pro-oxidative DEP chemicals induce protein unfolding/misfolding that lead to UPR and proinflammatory effects in a cell type that is targeted by PM in the lung.
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