Hyperosmotic stress up-regulates the expression of major vault protein in SW620 human colon cancer cells.
The major vault protein (MVP) is the major constituent of the vault particle, the largest ribonuclear protein complex described to date and is identical to lung resistance-related protein (LRP). Although MVP is also expressed in several normal tissues, little is known about its physiological role. MVP played a protective role against some xenobiotics and other stresses. We thus investigated the effect of osmotic stress on MVP expression by treating human colon cancer SW620 cells with sucrose or NaCl. The expression level of both MVP protein and MVP mRNA was increased by the osmostress. Sucrose or sodium chloride could also enhance MVP promoter activity. Inhibition of p38 MAPK in SW620 cells by SB203580 inhibited the expression of MVP under hyperosmotic stress. These findings suggested that osmotic stress up-regulated the MVP expression through p38 MAPK pathway. Down-regulation of MVP expression by MVP interfering RNA (RNAi) in SW620 cells increased the sensitivity of the cells to hyperosmotic stress and enhanced apoptosis. Furthermore, MVP RNAi prevented the osmotic stress-induced, time-dependent increase in phosphorylated Akt. These findings suggest that the PI3K/Akt pathway might be implicated in the cytoprotective effect of MVP. Our data demonstrate that exposure of cells to hyperosmotic stress induces MVP that might play an important role in the protection of the cells from the adverse effects of osmotic stress.
Ikeda
Ryuji
R
Department of Clinical Pharmacy and Pharmacology, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan.
Iwashita
Ken-ichi
K
Sumizawa
Tomoyuki
T
Beppu
Shun-ichi
S
Tabata
Sho
S
Tajitsu
Yusuke
Y
Shimamoto
Yuichi
Y
Yoshida
Kenichi
K
Furukawa
Tatsuhiko
T
Che
Xiao-Fang
XF
Yamaguchi
Tatsuya
T
Ushiyama
Mina
M
Miyawaki
Akihiko
A
Takeda
Yasuo
Y
Yamamoto
Masatatsu
M
Zhao
Hong-Ye
HY
Shibayama
Yoshihiko
Y
Yamada
Katsushi
K
Akiyama
Shin-ichi
S
D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival; D002867:Chromones / Q000378:metabolism; D003110:Colonic Neoplasms / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000378:metabolism; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D006801:Humans; D009025:Morpholines / Q000378:metabolism; D009997:Osmotic Pressure; D011401:Promoter Regions, Genetic; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D012965:Sodium Chloride / Q000378:metabolism; D013395:Sucrose / Q000378:metabolism; D020394:Vault Ribonucleoprotein Particles / Q000235:genetics / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D000099187:Major Vault Protein
D002867:Chromones; D004791:Enzyme Inhibitors; D009025:Morpholines; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D012965:Sodium Chloride; D013395:Sucrose; D020394:Vault Ribonucleoprotein Particles; D048051:p38 Mitogen-Activated Protein Kinases; D000099187:Major Vault Protein; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one