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Albumin Protects Lung Cells against Acrolein Cytotoxicity and Acrolein-Adducted Albumin Increases Heme Oxygenase 1 Transcripts
journal contribution
posted on 2020-06-29, 18:11 authored by Kiflai Bein, Rahel L. Birru, Heather Wells, Theodore P. Larkin, Pamela S. Cantrell, Matthew V. Fagerburg, Xuemei Zeng, George D. LeikaufAlbumin
is an abundant protein in the lung lining fluid that forms
an interface between lung epithelial cells and the external environment.
In the lung, albumin can be targeted for adduction by inhaled acrolein.
Acrolein, an α,β-unsaturated aldehyde, reacts with biomolecules
via Michael addition at the β-carbon or Schiff base formation
at the carbonyl carbon. To gain insight into acrolein’s mode
of action, we investigated in vitro albumin–acrolein
reactivity and the consequence of albumin adduction by acrolein on
cytotoxicity and transcript changes in NCI-H441 and human airway epithelial
cells (HAEC). Albumin protected NCI-H441 cells from acrolein toxicity.
In addition, albumin inhibited acrolein-induced increase of transcripts
associated with cellular stress response, activating transcription
factor 3 (ATF3), and antioxidant response, heme oxygenase 1 (HMOX1)
in HAEC cells. Acrolein-adducted albumin itself increased HMOX1 transcripts
but not ATF3 transcripts. The HMOX1 transcript increase was inhibited
by hydralazine, a carbonyl scavenger, suggesting that the carbonyl
group of acrolein-adducted albumin mediated HMOX1 transcript increase.
In acutely exposed C57BL/6J mice, bronchoalveolar lavage protein carbonylation
increased. Acrolein-adducted albumin Cys34 was identified by nLC-MS/MS.
These findings indicate that adduction of albumin by acrolein confers
a cytoprotective function by scavenging free acrolein, decreasing
a cellular stress response, and inducing an antioxidant gene response.
Further, these results suggest that β-carbon reactivity may
be required for acrolein’s cytotoxicity and ATF3 transcript
increase, and the carbonyl group of acrolein-adducted albumin can
induce HMOX1 transcript increase.
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Keywords
antioxidant gene responseAcrolein-Adducted Albumin Increases...HMOX 1 transcript increaseAlbumin Protects Lung CellsATF 3 transcriptsHAECstress responseβ- carbon reactivitySchiff base formationheme oxygenase 1ATF 3 transcript increaseNCI-H 441 cellsHMOX 1 transcriptsairway epithelial cellsAcrolein-adducted albumin Cys 34C 57BL micebronchoalveolar lavage protein carb...acrolein-adducted albumintranscription factor 3lung epithelial cellscarbonyl group
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