Androgen-mediated apoptosis of kidney tubule cells: role of c-Jun amino terminal kinase.
The incidence and the rate of progression of chronic kidney diseases (CKD) are for most diseases greater in men than in age-matched women. We have previously shown that testosterone (T) promotes the apoptosis of proximal tubule kidney cells. To better understand the downstream signaling process associated with T-induced apoptosis, we examined the involvement of c-Jun amino terminal kinase (JNK) in a human proximal tubule cell line (HK-2) exposed to T: JNK and its downstream effector c-Jun were rapidly phosphorylated. By blocking androgen receptor, JNK phosphorylation was reduced and 17beta-Estradiol treatment had no effect on it. Similarly, pre-treatment with the JNK inhibitor SP600125 prevented the T-induced apoptosis, the phosphorylation of c-Jun and the upregulation of the Fas/FADD pathway. These data show that the JNK/c-Jun pathway is directly regulated by androgens in vitro and highlight a potential mechanism explaining the reported gender differences in the progression of renal diseases.
Verzola
Daniela
D
Department of Internal Medicine, Nephrology Division, Genoa University, Viale Benedetto XV, 6, Genoa, Italy.
Villaggio
Barbara
B
Procopio
Vanessa
V
Gandolfo
Maria Teresa
MT
Gianiorio
Fabio
F
Famà
Annamaria
A
Tosetti
Fanny
F
Traverso
Paolo
P
Deferrari
Giacomo
G
Garibotto
Giacomo
G
D000726:Androgen Antagonists / Q000494:pharmacology; D059002:Androgen Receptor Antagonists; D000728:Androgens / Q000494:pharmacology / Q000502:physiology*; D017209:Apoptosis; D002467:Cell Nucleus / Q000201:enzymology; D004958:Estradiol / Q000494:pharmacology; D053222:Fas Ligand Protein / Q000096:biosynthesis; D053200:Fas-Associated Death Domain Protein / Q000096:biosynthesis; D005485:Flutamide / Q000494:pharmacology; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D007684:Kidney Tubules / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D008297:Male; D010766:Phosphorylation / Q000187:drug effects; D013739:Testosterone / Q000494:pharmacology / Q000502:physiology*; D019014:fas Receptor / Q000096:biosynthesis
D000726:Androgen Antagonists; D059002:Androgen Receptor Antagonists; D000728:Androgens; C505533:FADD protein, human; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D053200:Fas-Associated Death Domain Protein; D019014:fas Receptor; D013739:Testosterone; D004958:Estradiol; D005485:Flutamide; D048031:JNK Mitogen-Activated Protein Kinases