|
KMID : 0043320030260121055
|
|
Archives of Pharmacal Research
2003 Volume.26 No. 12 p.1055 ~ p.1060
|
|
|
Lisophosphatidic Acid Inhibits Melanocyte Proliferation via Cell Cycle Arrest
|
|
Kim Dong-Seok
Kwon Sun-Bang
Park Eun-Sang
Youn Sang-Woong
Park Kyoung-Chan
Park Seo-Hyoung
Kim Sung-Eun
|
|
|
Abstract
|
|
|
|
Lysophosphatidic acid (LPA) is a well-known mitogen in various cell types. However, we found that LPA inhibits melanocyte proliferation. Thus, we further investigated the possible signaling pathways involved in melanocyte growth inhibition. We first examined the regulation of the three major subfamilies of mitogen-activated protein (MAP) kinases and of the Akt pathway by LPA. The activations of extracellular signal-regulated protein kinase (ERK) and c-Jun N-terminal kinase (JNK) were observed in concert with the inhibition of melanocyte proliferation by LPA, whereas p38 MAP kinase and Akt were not influenced by LPA. However, the specific inhibition of the ERK or JNK pathways by PD98059 or D-JNKI1, respectively, did not restore the antiproliferative effect. We next examined changes in the expression of cell cycle related proteins. LPA decreased cyclin levels but increased (p21) and (p27) levels, which are known inhibitors of cyclin-dependent kinase. Flow cytometric analysis showed the inhibition of DNA synthesis by a reduction in the S phase and an increase in the phase of the cell cycle. Our results suggest that LPA induces cell cycle arrest by regulating the expressions of cell cycle related proteins.
|
|
|
KEYWORD
|
|
|
Lysophosphatidic acid, Proliferation, ERK/JNK, Cell cycle
|
|
|
FullTexts / Linksout information
|
|
|
|
|
|
Listed journal information
|
|
  
|