Urotensin II exerts antiapoptotic effect on NRK-52E cells through prostacyclin-mediated peroxisome proliferator-activated receptor alpha and Akt activation.
Urotensin II (UII) is a cyclic vasoactive peptide which is mainly expressed in kidneys. Although elevated plasma UII levels are associated with renal impairment, the influence of UII on renal injury is unclear. In this study, we monitored the influence of UII on gentamicin-induced apoptosis in rat tubular cells (NRK-52E). We found that UII significantly reduced gentamicin-induced apoptosis and apoptotic signals. Blocking endogenous UII secretion caused cells to be more susceptible to gentamicin. In gentamicin-treated mice, UII also expressed protective effect on renal tubular cells. UII was also found to induce prostacyclin (PGI2) production, which caused peroxisomal proliferator-activated receptor α (PPARα) activation as revealed by both PGI2 synthase siRNA transfection and piroxicam treatment. Blockage of PPARα by siRNA transfection inhibited UII-induced Akt phosphorylation and the antiapoptotic effect of UII. Our results suggest that UII can protect renal tubular cells from gentamicin-induced apoptosis through PGI2-mediated PPARα and Akt activation.
Division of Nephrology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan.
Yung-Ho
YH
Hsu
Tso-Hsiao
TH
Chen
Yen-Cheng
YC
Chen
Chung-Yi
CY
Cheng
Yuh-Mou
YM
Sue
Jia-Rung
JR
Chen
Cheng-Hsien
CH
Chen
D000818:Animals; D017209:Apoptosis; D002460:Cell Line; D004789:Enzyme Activation; D011464:Epoprostenol / Q000378:metabolism / Q000502:physiology*; D007686:Kidney Tubules, Distal / Q000502:physiology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D047493:PPAR alpha / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D015398:Signal Transduction; D015854:Up-Regulation; D014579:Urotensins / Q000502:physiology*
D047493:PPAR alpha; D043562:Receptors, G-Protein-Coupled; D014579:Urotensins; C512325:urotensin II receptor, mouse; C029677:urotensin II; D011464:Epoprostenol; D051057:Proto-Oncogene Proteins c-akt
6-keto-PGF1α; 6-keto-prostaglandin F1α; Akt; Apoptosis; CKD; ESRD; IP; IV; PGI(2); PI; PI3K; PPARα; Peroxisome proliferator-activated receptor alpha (PPARα); Prostacyclin; TUNEL; UII; Urotensin II; chronic kidney disease; end-stage renal disease; intraperitoneal injection; intravenous injection; peroxisome proliferator-activated receptor alpha; phosphatidylinositol 3-kinase; propidium iodide; prostacyclin; terminal deoxynucleotidyl transferase dUTP nick end labeling; urotensin II