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Modulation of keratinocyte expression of antioxidants by 4-hydroxynonenal, a lipid peroxidation end product.

Jeffrey D. Laskin, Ph.D. - Sat, 05/17/2014 - 02:00

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Modulation of keratinocyte expression of antioxidants by 4-hydroxynonenal, a lipid peroxidation end product.

Toxicol Appl Pharmacol. 2014 Mar 1;275(2):113-21

Authors: Zheng R, Heck DE, Mishin V, Black AT, Shakarjian MP, Kong AN, Laskin DL, Laskin JD

Abstract
4-Hydroxynonenal (4-HNE) is a lipid peroxidation end product generated in response to oxidative stress in the skin. Keratinocytes contain an array of antioxidant enzymes which protect against oxidative stress. In these studies, we characterized 4-HNE-induced changes in antioxidant expression in mouse keratinocytes. Treatment of primary mouse keratinocytes and PAM 212 keratinocytes with 4-HNE increased mRNA expression for heme oxygenase-1 (HO-1), catalase, NADPH:quinone oxidoreductase (NQO1) and glutathione S-transferase (GST) A1-2, GSTA3 and GSTA4. In both cell types, HO-1 was the most sensitive, increasing 86-98 fold within 6h. Further characterization of the effects of 4-HNE on HO-1 demonstrated concentration- and time-dependent increases in mRNA and protein expression which were maximum after 6h with 30 μM. 4-HNE stimulated keratinocyte Erk1/2, JNK and p38 MAP kinases, as well as PI3 kinase. Inhibition of these enzymes suppressed 4-HNE-induced HO-1 mRNA and protein expression. 4-HNE also activated Nrf2 by inducing its translocation to the nucleus. 4-HNE was markedly less effective in inducing HO-1 mRNA and protein in keratinocytes from Nrf2-/- mice, when compared to wild type mice, indicating that Nrf2 also regulates 4-HNE-induced signaling. Western blot analysis of caveolar membrane fractions isolated by sucrose density centrifugation demonstrated that 4-HNE-induced HO-1 is localized in keratinocyte caveolae. Treatment of the cells with methyl-β-cyclodextrin, which disrupts caveolar structure, suppressed 4-HNE-induced HO-1. These findings indicate that 4-HNE modulates expression of antioxidant enzymes in keratinocytes, and that this can occur by different mechanisms. Changes in expression of keratinocyte antioxidants may be important in protecting the skin from oxidative stress.

PMID: 24423726 [PubMed - indexed for MEDLINE]

Categories: Publications from UCDPER Members

Oxidative stress-induced autophagy: role in pulmonary toxicity.

Jeffrey D. Laskin, Ph.D. - Sat, 05/17/2014 - 02:00

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Oxidative stress-induced autophagy: role in pulmonary toxicity.

Toxicol Appl Pharmacol. 2014 Mar 1;275(2):145-51

Authors: Malaviya R, Laskin JD, Laskin DL

Abstract
Autophagy is an evolutionarily conserved catabolic process important in regulating the turnover of essential proteins and in elimination of damaged organelles and protein aggregates. Autophagy is observed in the lung in response to oxidative stress generated as a consequence of exposure to environmental toxicants. Whether autophagy plays role in promoting cell survival or cytotoxicity is unclear. In this article recent findings on oxidative stress-induced autophagy in the lung are reviewed; potential mechanisms initiating autophagy are also discussed. A better understanding of autophagy and its role in pulmonary toxicity may lead to the development of new strategies to treat lung injury associated with oxidative stress.

PMID: 24398106 [PubMed - indexed for MEDLINE]

Categories: Publications from UCDPER Members

Exposure science: a need to focus on conducting scientific studies, rather than debating its concepts.

Paul J. Lioy, Ph.D. - Thu, 05/15/2014 - 14:00

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Exposure science: a need to focus on conducting scientific studies, rather than debating its concepts.

J Expo Sci Environ Epidemiol. 2013 Sep-Oct;23(5):455-6

Authors: Lioy PJ

PMID: 23963520 [PubMed - indexed for MEDLINE]

Categories: Publications from UCDPER Members

Interconversion of chromium species during air sampling: effects of O3, NO2, SO2, particle matrices, temperature, and humidity.

Paul J. Lioy, Ph.D. - Thu, 05/15/2014 - 14:00

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Interconversion of chromium species during air sampling: effects of O3, NO2, SO2, particle matrices, temperature, and humidity.

Environ Sci Technol. 2013 May 7;47(9):4408-15

Authors: Huang L, Fan ZT, Yu CH, Hopke PK, Lioy PJ, Buckley BT, Lin L, Ma Y

Abstract
The interconversion between Cr(VI), a pulmonary carcinogen, and Cr(III), an essential human nutrient, poses challenges to the measurement of Cr(VI) in airborne particles. Chamber and field tests were conducted to identify the factors affecting Cr(VI)-Cr(III) interconversion in the basic filter medium under typical sampling conditions. In the chamber tests, isotopically enriched (53)Cr(VI) and (50)Cr(III) were spiked on diesel particulate matter (DPM) and secondary organic aerosol (SOA) that were precollected on a basic MCE filter. The filter samples were then exposed to clean air or the air containing SO2 (50 and 160 ppb), 100 ppb O3, or 150 ppb NO2 for 24 h at 16.7 LPM flow rate at designated temperature (20 and 31 °C) and RH (40% and 70%) conditions. Exposure to 160 ppb SO2 had the greatest effect on (53)Cr(VI) reduction, with (53)Cr(VI) recovery of 31.7 ± 15.8% (DPM) and 42.0 ± 7.9% (SOA). DPM and SOA matrix induced (53)Cr(VI) reduction when exposed to clean air while reactive oxygen species in SOA could promote (50)Cr(III) oxidation. Deliquescence when RH increased from 40% to 70% led to conversion of Cr(III) in SOA, whereas oxidized organics in DPM and SOA enhanced hygroscopicity and thus facilitated Cr(VI) reduction. Field tests showed seasonal variation of Cr(VI)-Cr(III) interconversion during sampling. Correction of the interconversion using USEPA method 6800 is recommended to improve accuracy of ambient Cr(VI) measurements.

PMID: 23550818 [PubMed - indexed for MEDLINE]

Categories: Publications from UCDPER Members