Malondialdehyde-acetaldehyde adducts decrease bronchial epithelial wound repair.
Most people who abuse alcohol are cigarette smokers. Previously, we have shown that malondialdehyde, an inflammation product of lipid peroxidation, and acetaldehyde, a component of both ethanol metabolism and cigarette smoke, form protein adducts that stimulate protein kinase C (PKC) activation in bronchial epithelial cells. We have also shown that PKC can regulate bronchial epithelial cell wound repair. We hypothesize that bovine serum albumin adducted with malondialdehyde and acetaldehyde (BSA-MAA) decreases bronchial epithelial cell wound repair via binding to scavenger receptors on bronchial epithelial cells. To test this, confluent monolayers of bovine bronchial epithelial cells were grown in serum-free media prior to wounding the cells. Bronchial epithelial cell wound closure was inhibited in a dose-dependent manner (up to 60%) in the presence of BSA-MAA than in media treated cells (Laboratory of Human Carcinogenesis [LHC]-9-Roswell Park Memorial Institute [RPMI]). The specific scavenger receptor ligand, fucoidan, also stimulated PKC activation and decreased wound repair. Pretreatment with fucoidan blocked malondialdehyde-acetaldehyde binding to bronchial epithelial cells. When bronchial epithelial cells were preincubated with a PKC alpha inhibitor, Gö 6976, the inhibition of wound closure by fucoidan and BSA-MAA was blocked. Western blot demonstrated the presence of several scavenger receptors on bronchial epithelial cell membranes, including SRA, SRBI, SRBII, and CD36. Scavenger receptor-mediated activation of PKC alpha may function to reduce wound healing under conditions of alcohol and cigarette smoke exposure where malondialdehyde-acetaldehyde adducts may be present.
Wyatt
Todd A
TA
Research Service, Department of Veterans Affairs Medical Center, 4101 Woolworth Avenue, Omaha, NE 68105, USA. twyatt@unmc.edu
Kharbanda
Kusum K
KK
Tuma
Dean J
DJ
Sisson
Joseph H
JH
Spurzem
John R
JR
D000079:Acetaldehyde / Q000378:metabolism*; D000818:Animals; D001980:Bronchi / Q000293:injuries* / Q000502:physiology; D002227:Carbazoles / Q000494:pharmacology; D002417:Cattle; D002460:Cell Line; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology; D004847:Epithelial Cells / Q000502:physiology; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D008315:Malondialdehyde / Q000378:metabolism*; D011485:Protein Binding; D011493:Protein Kinase C / Q000502:physiology; D051116:Receptors, Scavenger / Q000032:analysis / Q000502:physiology; D014945:Wound Healing
D002227:Carbazoles; D007211:Indoles; D051116:Receptors, Scavenger; C081021:Go 6976; D008315:Malondialdehyde; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D000079:Acetaldehyde