Abstract
Particulate matter (PM) modulates the expression of autophagy; however, the role of selective autophagy by PM remains unclear. The objective of this study was to determine the underlying mechanisms in protein oxidation and degradation caused by PM. Human epithelial A549 cells were exposed to diesel exhaust particles (DEPs), urban dust (UD), and carbon black (CB; control particles). Cell survival and proliferation were significantly reduced by DEPs and UD in A549 cells. First, benzo(a)pyrene diolepoxide (BPDE) protein adduct was caused by DEPs at 150 μg/ml. Methionine oxidation (MetO) of human albumin proteins was induced by DEPs, UD, and CB; however, the protein repair mechanism that converts MetO back to methionine by methionine sulfoxide reductases A (MSRA) and B3 (MSRB3) was activated by DEPs and inhibited by UD, suggesting that oxidized protein was accumulating in cells. As to the degradation of oxidized proteins, proteasome and autophagy activation was induced by CB with ubiquitin accumulation, whereas proteasome and autophagy activation was induced by DEPs without ubiquitin accumulation. The results suggest that CB-induced protein degradation may be via an ubiquitin-dependent autophagy pathway, whereas DEP-induced protein degradation may be via an ubiquitin-independent autophagy pathway. A distinct proteotoxic effect may depend on the physicochemistry of PM.
Highlights
Particulate matter (PM) modulates the expression of autophagy; the role of selective autophagy by PM remains unclear
The size of diesel exhaust particles (DEPs) was significantly smaller than those of carbon black (CB) and urban dust (UD) according to Field emission-scanning electron microscopy (FE-SEM) images, whereas UD had the largest size among these particles
Five major findings are reported in the present study: (1) cell survival and proliferation were significantly reduced by DEPs and UD; (2) methionine oxidation (MetO) occurred after CB, DEP, and UD exposure; (3) the protein repair mechanism that converts methionine sulfoxide (MetO) back to methionine by methionine sulfoxide reductase A (MSRA) and MSRB3 was activated by DEPs and inhibited by UD; (4) proteasome and autophagy activation was induced by CB with ubiquitin accumulation, whereas proteasome and autophagy activation was induced by DEPs without ubiquitin accumulation; and (5) CB-induced protein degradation was via a ubiquitin-dependent autophagy pathway, whereas DEP-induced protein degradation was via a ubiquitin-independent autophagy pathway
Summary
Particulate matter (PM) modulates the expression of autophagy; the role of selective autophagy by PM remains unclear. Pardo and colleagues showed that repeated exposure to urban PM caused protein oxidation in mouse lungs[9]. Those authors suggested that chemical compounds may be important in regulating protein oxidation. 90% of damaged proteins are degraded into small peptides by the ubiquitin-proteasome pathway[12], which plays a critical role in removing oxidized proteins and maintaining biological systems in a healthy status. Human studies showed that acute exposure to diesel exhaust and secondary organic aerosols reduced proteasome activity in peripheral blood cells[14,15], suggesting that proteasomes are an important mechanism in response to acute exposure of air pollution
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