Phosphorylation of caveolin-1 is anti-apoptotic and promotes cell attachment during oxidative stress of kidney cells.
OBJECTIVE
Caveolin-1 (cav1) is reported to have both cell survival and pro-apoptotic characteristics. This may be explained by its localisation or phosphorylation in injured cells. This study investigated the role of cav1 in kidney cells of different nephron origin and developmental state after oxidative stress.


METHODS
Renal MCDK distal tubular, HK2 proximal tubular epithelial cells and HEK293T renal embryonic cells were treated with 1 mM hydrogen peroxide. Apoptosis, loss of cell adhesion, and cell survival were compared with expression of cav1 in its non-phosphorylated and phosphorylated (p-cav1) forms. Cav1 was transfected into the HEK293T cells, or caveolae were disrupted with filipin or nystatin in HK2 cells, to investigate functions of cav1 and p-cav1.


RESULTS
Oxidative stress induced more apoptosis in HK2s than MDCKs (p < 0.05). HK2s had lower endogenous cav1 and p-cav1 than MDCKs (p < 0.05). Both cell lines had increased p-cav1, but not cav1, with oxidative stress. This increase was greatest in MDCKs (p < 0.01). Cav1 was located mainly in the plasma membrane of untreated cells and translocated to the cytoplasm with oxidative stress in both cell lines, more so in MDCKs. Disruption of caveolae caused cytoplasmic translocation of cav1 in HK2s, but did not alter high levels of oxidative stress-induced apoptosis. When HEK293Ts lacking endogenous cav1 were transfected with cav1, oxidant-induced apoptosis and loss of cell adhesion was decreased (p < 0.01), and p-cav1 was induced by treatment.


CONCLUSIONS
Cav1 expression and localisation in kidney cells is not anti-apoptotic, but increased expression of p-cav1 may promote cell survival after oxidative stress.
Percy
Christine J
CJ
Molecular and Cellular Pathology, School of Medicine, University of Queensland, Brisbane, Queensland, Australia.
Pat
Betty K
BK
Healy
Helen
H
Johnson
David W
DW
Gobe
Glenda C
GC
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D015153:Blotting, Western; D051242:Caveolin 1 / Q000378:metabolism*; D002448:Cell Adhesion / Q000502:physiology; D002460:Cell Line; D002470:Cell Survival; D004285:Dogs; D005455:Fluorescent Antibody Technique; D006801:Humans; D007684:Kidney Tubules / Q000166:cytology / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology*; D010766:Phosphorylation
D051242:Caveolin 1