Abstract Influence of extracellular calcium on the transcription of peroxisome proliferator activated receptor alpha (PPAR a) and acyl coenzyme A oxidase (ACOX)

N.S. Yaacob^1* and M.N. Norazymi²

¹Department of Chemical Pathology, School of Medical Sciences and 2School of Health Sciences, Universiti Sains
Malaysia, 16150 Kubang Kerian, Kelantan, Malaysia

Received 9 March 2000 / Accepted 28 July 2000

Abstract.
The influence of extracellular calcium (Ca²⁺) on the peroxisome proliferator induced transcription of the peroxisome proliferator activated receptor alpha (PPARa) and the PPARa regulated peroxisomal enzyme, acyl coenzyme A oxidase (ACOX) in rat primary hepatocyte cultures were investigated using a competitive RT PCR method. In the presence of extracellular Ca²⁺, treatment with the peroxisome proliferators, Wyl4,643 and clofibrate, caused an increase in the level of PPARa mRNA by 2.4 fold (p < 0.005) and 1.8 fold (p < 0.05) respectively. However, in Ca²⁺ depleted cultures, Wyl4,643 and clofibrate did not increase the level of PPARa mRNA which remained significantly lower than the corresponding Ca²⁺ containing cultures (p < 0.005 and p < 0.05 respectively). The level of ACOX mRNA was also increased by Wyl4,643 (3.6 fold; p < 0.005) and clofibrate (3.9 fold; p < 0.005) in the presence of Ca²⁺. In Ca²⁺ depleted cultures, the level of ACOX mRNA in Wyl4,643 treated hepatocytes remained the same although cultures treated with clofibrate had partially reduced levels of ACOX mRNA (p < 0.01) but still remained higher than control values (p < 0.02). The results showed that whilst the transcription of PPARa may be dependent on Ca²⁺, that of ACOX may only be partially dependent or independent of Ca2+ This indicates that PPARa transcription but not necessarily its function, may be regulated by a Ca²⁺ dependent signal transduction pathway.

Keywords: Acyl coenzyme A oxidase, calcium, PCR MIMIC, peroxisome proliferator, PPARa