Effect of beta-carotene on the expression of 3-hydroxy-3-methylglutaryl coenzyme A reductase in rat liver.
3-Hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase), is a rate-limiting enzyme in the biosynthesis of not only cholesterol but also a variety of non-sterol isoprenoids. It is subjected to multivalent feedback suppression by transcriptional and post-transcriptional control mechanisms mediated by sterols and non-sterol substances. In the present study, the effect of a plant isoprenoid, beta-carotene, on the expression of HMG-CoA reductase in rat liver was investigated. In control rats the hepatic levels of mRNA transcripts of HMG-CoA reductase increased following 2/3 partial hepatectomy with two peaks, one at 8 h and the other at 24 h. Administration of the carotenoid (70 mg/kg, given every alternate day for 3 consecutive weeks) partially inhibited the increase in the transcript level with a 50% reduction at 8 h and 30% reduction at 24 h post partial hepatectomy. Nuclear run-off assays with nuclei isolated from the resting liver and from livers of control rats and rats exposed to beta-carotene for 3 consecutive weeks and killed 8 h after partial hepatectomy indicated that beta-carotene did not inhibit the rate of transcription of HMG-CoA reductase gene. These observations suggest that beta-carotene regulates the expression of HMG-CoA reductase by some post-transcriptional mechanisms.
Moreno
F S
FS
Departmento de Alimentos e Nutricao, Experimental, Faculdade de Ciéncias, Farmacêuticas, Universidade de São Paulo, Brazil.
Rossiello
M R
MR
Manjeshwar
S
S
Nath
R
R
Rao
P M
PM
Rajalakshmi
S
S
Sarma
D S
DS
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D015152:Blotting, Northern; D002338:Carotenoids / Q000494:pharmacology*; D002467:Cell Nucleus / Q000378:metabolism; D005246:Feedback; D015870:Gene Expression / Q000187:drug effects*; D006498:Hepatectomy; D006903:Hydroxymethylglutaryl CoA Reductases / Q000096:biosynthesis*; D008297:Male; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D011916:Rats, Inbred F344; D012016:Reference Values; D014158:Transcription, Genetic / Q000187:drug effects; D019207:beta Carotene
D000970:Antineoplastic Agents; D012333:RNA, Messenger; D019207:beta Carotene; D002338:Carotenoids; D006903:Hydroxymethylglutaryl CoA Reductases