Phosphatidylinositol 3-kinase/nuclear factor-kappa B signaling pathway is involved in the regulation of IGF-I on Fas-associated death domain-like interleukin-1-converting enzyme-inhibitory protein expression in cultured FRTL thyroid cells.
It is known that decreased apoptosis of thyrocytes may be involved in the formation of goiters in patients with Graves' disease, and growth factors are involved in regulating the size of the thyroid gland. The purpose of our study was to investigate mRNA and protein levels of an antiapoptotic protein, namely, Fas-associated death domain-like interleukin-1-converting enzyme (FLICE)-inhibitory protein (FLIP). The results showed that in FRTL thyroid cells, treatment with IGF-I upregulated mRNA and protein levels of FLIP in a dose-dependant manner. While a specific nuclear factor-kappaB (NF-kappaB) inhibitor, BAY11-7082, blocked this effect. Further study demonstrated that IGF-I induced the DNA-binding activity of NF-kappaB in association with decreased expression of the NF-kappaB inhibitory protein IkappaBalpha . These findings implied that IGF-I increased FLIP expression by enhancing the activation of NF-kappaB in FRTL thyroid cells. Using a specific phosphatidylinositol 3-kinase (PI3K) inhibitor, LY294002, we also found that PI3K was involved in the pathway by which IGF-I activated NF-kappaB and increased FLIP expression. When treated with IGF-I and LY294002, decreased NF-kappaB DNA binding activity and increased expression of IkappaBalpha protein were detected in cultured thyroid cells, which further confirmed that NF-kappaB was under the control of the PI3K pathway. Taken together, our results suggest that IGF-I regulates the expression of FLIP in FRTL cells by activating the PI3K/NF-kappaB cascade.
Ren
Meng
M
Central Laboratory, Shandong University, Jinan, China.
Guan
Qingbo
Q
Zhong
Xia
X
Gong
Bendi
B
Sun
Ying
Y
Xin
Wei
W
Guo
Jun
J
Wang
Hai
H
Gao
Ling
L
Zhao
Jiajun
J
D053446:CASP8 and FADD-Like Apoptosis Regulating Protein / Q000096:biosynthesis / Q000235:genetics; D020170:Caspase 1 / Q000378:metabolism*; D061945:Caspase Inhibitors; D002460:Cell Line; D053200:Fas-Associated Death Domain Protein / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism / Q000502:physiology*; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D013961:Thyroid Gland / Q000166:cytology / Q000201:enzymology*; D015854:Up-Regulation / Q000235:genetics
D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; D061945:Caspase Inhibitors; D053200:Fas-Associated Death Domain Protein; D016328:NF-kappa B; D007334:Insulin-Like Growth Factor I; D019869:Phosphatidylinositol 3-Kinases; D020170:Caspase 1