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Human Keratinocyte Responses to Woodsmoke

ABSTRACT: Air pollution consists of complex mixtures of chemicals with serious deleterious health effects from acute and chronic exposure. To help understand mechanisms by which adverse effects occur, present work examines responses of cultured human epidermal keratinocytes to specific chemicals commonly found in woodsmoke. Our earlier findings with liquid smoke flavoring (aqueous extract of charred wood) revealed that such extracts stimulated expression of genes associated with oxidative stress and proinflammatory response, activated the aryl hydrocarbon receptor, thereby inducing cytochrome P4501A1 activity, and induced cross-linked envelope formation, a lethal event ordinarily occurring during terminal differentiation. Present results showed that furfural produced transcriptional responses resembling those of liquid smoke, cyclohexanedione activated the aryl hydrocarbon receptor, and several chemicals induced envelope formation. Of these, syringol permeabilized the cells to egress of lactate dehydrogenase at a concentration close to that yielding envelope formation, while furfural induced envelope formation without permeabilization detectable in this way. Furfural (but not syringol) stimulated incorporation of amines into cell protein in extracts in the absence of transglutaminase activity. Nevertheless, both chemicals substantially increased the amount of cellular protein incorporated into envelopes and greatly altered the envelope protein profile. Moreover, the proportion of keratins in envelopes was dramatically increased. These findings are consistent with chemically induced protein cross-linking in the cells. Elucidating mechanisms by which this phenomenon occurs may help interpret bioassays of complex pollutant mixtures and suggest additional sensitive ways to monitor exposures.

INSTRUMENT(S): Q Exactive Plus

ORGANISM(S): Homo Sapiens (ncbitaxon:9606)

SUBMITTER: Robert H. Rice

PROVIDER: MSV000093227 | MassIVE | Wed Nov 01 11:06:00 GMT 2023

SECONDARY ACCESSION(S): PXD046590

REPOSITORIES: MassIVE

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Human Keratinocyte Responses to Woodsmoke

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