Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
2004-10-6
pubmed:abstractText
We demonstrated previously that smoke exposure and/or high-dose beta-carotene supplementation decreases levels of retinoic acid and retinoic acid receptor beta (RARbeta) protein, but increase levels of c-Jun and proliferating cellular nuclear antigen protein in the lungs of ferrets. In contrast, low-dose beta-carotene can prevent the decreased lung retinoic acid and the smoke-induced lung lesions. In the present study, we investigated whether smoke exposure and/or beta-carotene supplementation could affect Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinase (MAPK), and p53 in the lungs of ferrets. Ferrets were subjected to cigarette smoke exposure and either a high or low dose of beta-carotene (2 x 3 factorial design) for 6 mo. There were greater protein levels of phosphorylated JNK, p38, and c-Jun, but lower levels of MAPK phophatase-1 (MKP-1) in groups exposed to smoke and/or high dose beta-carotene. Both phosphorylated-p53 and total p53 were substantially increased in the lungs of these groups. In contrast, low-dose beta-carotene greatly attenuated the smoke-induced phosphorylation of JNK, p38, c-Jun, p53, and total p53, accompanied by upregulated MKP-1. Smoke exposure increased MAPK kinase-4 (MKK4) phosphorylation regardless of beta-carotene supplementation. These data indicate that restoration of retinoic acid and MKP-1 by low-dose beta-carotene in the lungs of ferrets may prevent the smoke-induced activation of the JNK-dependent signaling pathway, p38 MAPK, and the associated phosphorylation of p53, thereby lowering the risk of the smoke-related lung lesions. These data provide supportive evidence that the beneficial vs. detrimental effects of beta-carotene supplementation are related to the dosage of beta-carotene administered.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0022-3166
pubmed:author
pubmed:issnType
Print
pubmed:volume
134
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2705-10
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Low dose beta-carotene supplementation of ferrets attenuates smoke-induced lung phosphorylation of JNK, p38 MAPK, and p53 proteins.
pubmed:affiliation
Nutrition and Cancer Biology Laboratory, Jean Mayer U.S. Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, Boston, MA 02111, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't