Introduction

The peroxisomal 3-oxoacyl-CoA thiolase (thiolase) is involved in the final reaction of fatty acids P-oxidation. The enzyme cleaves long chain fatty acyl-CoA to generate acetyl-CoA and chain-shortened acyl-CoA. The importance of studying thiolase is that it generates acetyl-CoA which is the precursor for the synthesis of molecules like cholesterol and fatty acids. It is now established that several genes mediate lipid metabolism in target organs like liver and adipose tissue, and are thus regulated by several Peroxisome Proliferator-Activated Receptors (PPARs).

In rat liver at least 3 genes encode for peroxisomal thiolase of which thiolase B is inducible by peroxisome proliferators.1 To elucidate the mechanism of induction of thiolase B, an upstream 2.8kb fragment containing the promoter element has been sub-cloned and partially sequenced. The sequence analysis reavealed a putative PPRE (Peroxisome Proliferator Response Element) AGACCT T TGAACC at -681 to -668.2,3

To analyzes the functional elements in the 2.8 kb fragment, several deletions were made in the 5' and the 3' region in a plasmid containing TK promoter and the sequence encoding luciferase. Transfection assays were performed with these various deleted constructs in HeLa cells. Preliminary transfection results seem to suggest that this localized PPRE element is not the only one in controlling thiolase B expression by PPARa.

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