The serum and glucocorticoid-regulated kinase 1 in hypoxic renal injury.
The serum- and glucocorticoid-inducible kinase 1 (SGK1) is a serine threonine protein kinase activated through the phosphatidylinositol 3-kinase (PI3-kinase) pathway and counteracting apoptosis. Protein expression and activation of SGK1 are increased in various models of cell stress. The present study explored the role of SGK1 in renal hypoxia/ischemia induced apoptosis. HEK 293 cells were exposed in vitro to hypoxia/reoxygenation (H/R), which increased SGK1 transcript levels, SGK1 protein abundance and SGK1 phosphorylation. H/R injury further enhanced the percentage of apoptotic cells, an effect significantly blunted by prior SGK1 overexpression. In vivo renal ischemia/reperfusion (I/R) injury increased SGK1 transcript levels and SGK1 protein abundance. I/R enhanced apoptosis, an effect significantly more pronounced in gene targeted mice lacking SGK1. In conclusion, SGK1 is up-regulated and counteracts apoptosis following H/R in vitro and ischemia In vivo.
Rusai
Krisztina
K
First Department of Pediatrics, Semmelweis University, Budapest, Hungary.
Wagner
Bettina
B
Roos
Marcel
M
Schmaderer
Christoph
C
Strobl
Matthias
M
Boini
Krishna M
KM
Grenz
Almut
A
Kuhl
Dietmar
D
Heemann
Uwe
U
Lang
Florian
F
Lutz
Jens
J
D000818:Animals; D017209:Apoptosis; D015687:Cell Hypoxia; D002460:Cell Line; D006801:Humans; D017874:Immediate-Early Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D020287:In Situ Nick-End Labeling; D007674:Kidney Diseases / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000099184:Serum-Glucocorticoid Regulated Kinases
D017874:Immediate-Early Proteins; D017346:Protein Serine-Threonine Kinases; D000099184:Serum-Glucocorticoid Regulated Kinases