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Ghrelin Inhibits High Glucose-Induced PC12 Cell Apoptosis by Regulating TLR4/NF-κB Pathway

Abstract

Ghrelin has a protective effect on diabetic encephalopathy. To expound the protective mechanism, we investigated the effects of ghrelin on high glucose-induced cell apoptosis and intracellular signaling in cultured PC12, which is a suitable model for studying neuronal cell death. High glucose-induced PC12 apoptosis was significantly inhibited by co-treatment of ghrelin. Sustaining inflammatory response is one of the molecular mechanisms of diabetic encephalopathy and TLR4 signaling has close relationship with inflammatory response. But there is no report about the biologic role of toll-like receptor 4/nuclear factor-κB (TLR4/NF-κB) signaling in controlling high glucose-induced PC12 apoptosis by ghrelin. In this study, we found that TLR4/NF-κB pathway was activated by high glucose stimulation in PC12 and significantly alleviated by the co-treatment of ghrelin. From these findings, we made the conclusion that ghrelin could attenuate the symptoms of diabetic encephalopathy, which alleviates inflammatory reaction of diabetic encephalopathy by regulating TLR4/NF-κB pathway.

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Abbreviations

TLR4/NF-κB:

Toll-like receptor 4/nuclear factor-κB

HG:

High glucose

TEM:

Transmission electron microscopy

FBS:

Fetal bovine serum

DMEM:

Dulbecco’s modified Eagle’s medium

DMSO:

Dimethyl sulfoxide

DEPC:

Diethylpyrocarbonate

SDS:

Sodium dodecyl sulfate

ECL:

Electrochemiluminescence

ATCC:

American Type Culture Collection

PBS:

Phosphate-buffered saline

MyD88:

Myeloid differentiation primary response gene 88

TRAF6:

Human tumor necrosis factor receptor-associated factor 6

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ACKNOWLEDGMENTS

Our work was supported by grants from both the Key Projects of Medical Science sponsored by Chongqing Municipal Health Bureau in the People’s Republic of China (2010-1-8) and the Natural Science Foundation of Chongqing in the People’s Republic of China (CSTC, 2010BB5396). The study is also supported by the National Foundation of Natural Science of China (no. 81170752).

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The authors declare no competing interests.

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Correspondence to Qian Xiao.

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Liu, X., Xiao, Q., Zhao, K. et al. Ghrelin Inhibits High Glucose-Induced PC12 Cell Apoptosis by Regulating TLR4/NF-κB Pathway. Inflammation 36, 1286–1294 (2013). https://doi.org/10.1007/s10753-013-9667-2

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KEY WORDS

  • PC12
  • ghrelin
  • high glucose
  • TLR4/NF-κB pathway
  • inflammation