The effect of hypoxia on the expression of 150 kDa oxygen-regulated protein (ORP 150) in HeLa cells.
Correct protein folding is an important factor, for the translocation of newly synthesised proteins to specific subcellular compartments, extracellular matrix or to biological fluids. This process is regulated by a group of specific proteins, referred to as chaperones. Many stress conditions, such as oxygen or glucose deprivation, slow down the folding process and cause accumulation of unfolded/misfolded proteins in the cell. Molecular chaperones are induced in these conditions; with some named as oxygen-regulated proteins (ORPs). These bind to unfolded / misfolded proteins to facilitate correct assembly. ORP 150 is the subject of this study. Hypoxia results in an enhancement of ORP 150 expression in several tumour cell lines cultured in vitro. HeLa cells grown in hypoxic conditions (despite an intensive expression of ORP 150) demonstrate higher rates of apoptosis in comparison to those cultured in normoxic conditions. Furthermore, the inhibition of ORP 150 synthesis by transfection of these cells with a specific siRNA resulted in an intensification of apoptosis, as indicated by specific markers of this process; the enhancement of poly ADP-ribose protein cleavage and the increase in Bim protein expression. We conclude from our study that the increase in ORP 150 synthesis protects the cells against the proapoptotic effect of hypoxia.
Novartis Oncology Department, Basel, Switzerland. mapasko@o2.pl
Marzanna
M
Cechowska-Pasko
Edward
E
Bankowski
Patrick
P
Chene
D017209:Apoptosis; D001483:Base Sequence; D015687:Cell Hypoxia / Q000235:genetics* / Q000502:physiology; D002460:Cell Line; D045744:Cell Line, Tumor; D015870:Gene Expression; D018840:HSP70 Heat-Shock Proteins; D006367:HeLa Cells; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D011506:Proteins / Q000235:genetics*; D034741:RNA, Small Interfering / Q000235:genetics; D014162:Transfection
C497442:HIF1A protein, human; D018840:HSP70 Heat-Shock Proteins; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D011506:Proteins; D034741:RNA, Small Interfering; C050087:oxygen-regulated proteins