High-density lipoprotein is a potential growth factor for adrenocortical cells

Koji Murao; Hitomi Imachi; Wenming Cao; Xiao Yu; Junhua Li; Kazuya Yoshida; Rania A M Ahmed; Kensuke Matsumoto; Takamasa Nishiuchi; Norman C W Wong; Toshihiko Ishida

doi:10.1016/j.bbrc.2006.03.131

High-density lipoprotein is a potential growth factor for adrenocortical cells

Biochem Biophys Res Commun. 2006 May 26;344(1):226-32. doi: 10.1016/j.bbrc.2006.03.131. Epub 2006 Mar 29.

Authors

Koji Murao¹, Hitomi Imachi, Wenming Cao, Xiao Yu, Junhua Li, Kazuya Yoshida, Rania A M Ahmed, Kensuke Matsumoto, Takamasa Nishiuchi, Norman C W Wong, Toshihiko Ishida

Affiliation

¹ Division of Endocrinology and Metabolism, Department of Internal Medicine, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe Miki-cho, Kita-gun, Kagawa, Japan. [email protected]

PMID: 16600185
DOI: 10.1016/j.bbrc.2006.03.131

Abstract

The entry of cholesterol contained within high-density lipoprotein (HDL) into adrenocortical cells is mediated by a human homologue of SR-BI, CD36, and LIMPII Analogous-1 (CLA-1) and thus augmenting their growth. To address the role of CLA-1, we created a mutant mCLA that lacked the C-terminal tail. HDL CE selective uptake by cells carrying the mCLA-1 receptor was fully active and equivalent to those transfected with full-length CLA-1 (fCLA-1). Expression of mCLA inhibited the proliferation of an adrenocortical cell line and the incorporation of [(3)H]thymidine into the cells. This effect was sensitive to wortmannin, an inhibitor of phosphoinositide 3-kinase (PI3K). Our transcriptional studies revealed that the inhibitory action of mCLA required the transcriptional factor AP-1 and the effect of HDL on AP-1 activation was also abrogated by wortmannin. These findings raise the possibility that the inhibitors of the effects of HDL may be of therapeutic value for adrenocortical tumor.

MeSH terms

Adrenal Cortex / cytology
Adrenal Cortex / drug effects*
Adrenal Cortex / metabolism
Androstadienes / pharmacology
Animals
Cell Line, Tumor
Cell Proliferation
Growth Substances / metabolism
Growth Substances / physiology*
Lipoproteins, HDL / metabolism
Lipoproteins, HDL / pharmacology*
Mice
Mutation
Phosphatidylinositol 3-Kinases / metabolism
Phosphoinositide-3 Kinase Inhibitors
Promoter Regions, Genetic
Proto-Oncogene Proteins c-akt / antagonists & inhibitors
Proto-Oncogene Proteins c-akt / metabolism
Scavenger Receptors, Class B / genetics
Scavenger Receptors, Class B / physiology*
Transcription Factor AP-1 / antagonists & inhibitors*
Transcription Factor AP-1 / genetics
Transcription Factor AP-1 / metabolism
Transcriptional Activation / drug effects
Wortmannin

Substances

Androstadienes
Growth Substances
Lipoproteins, HDL
Phosphoinositide-3 Kinase Inhibitors
Scarb1 protein, mouse
Scavenger Receptors, Class B
Transcription Factor AP-1
Proto-Oncogene Proteins c-akt
Wortmannin