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Biomed Pharmacother. 2018 Feb;98:63-68. doi: 10.1016/j.biopha.2017.11.142. Epub 2017 Dec 12.

Lin28a functionally modulates bupivacaine-induced dorsal root ganglion neuron apoptosis through TrkA activation.

Author information

1
Department of Anesthesiology, Huangshi AiKang Hospital, Huangshi, 435000, China.
2
Department of Anesthesiology, People's Hospital of Shenzhen, Shenzhen, 518000, China.
3
Department of Anesthesiology, Huangshi Maternity and Children's Health Hospital, Edong Health care Group, 80 South Guilin Rd., Huangshi, 435000, China. Electronic address: tangb118@aol.com.

Abstract

PURPOSE:

Lin-28 Homolog A gene (Lin28a) is an important regulator in nerve system. In this study, we investigated the functional mechanism of Lin28a during the process of bupivacaine (BUP)-induced neuronal apoptosis of spinal cord dorsal root ganglion neurons (DRGNs).

METHODS:

Young mouse DRGNs were cultured in vitro and treated with series concentrations of BUP. Apoptosis was evaluated by TUNEL assay. Corresponding Lin28a mRNA and protein expressions were evaluated by qRT-PCR and western blot (WB) assays. Lin28a was downregulated by siRNA and its effect on BUP (5 mM)-induced DRGN apoptosis was measured by qRT-PCR, WB and TUNEL assays, respectively. Alternatively, Lin28a was upregulated in DRGNs. It's effect on BUP (0.1 mM)-induced DRGN apoptosis was also measured. Finally, WB was used to examine Caspase-3/9 and TrkA protein expressions in Lin28a-downregualted and BUP-injured DRGN to explore Lin28a-associated signaling pathways.

RESULTS:

In DRGN in vitro culture, 0.1 mM BUP induced moderate neuronal apoptosis while 5 mM BUP induced significant apoptosis. Lin28a mRNA and protein were both upregulated by BUP, in concentration-dependent manner. Functional assays showed that Lin28a downregulation rescued 5 mM BUP-induced neuronal apoptosis, whereas Lin28a upregulation aggravated 0.1 mM BUP-induced neuronal apoptosis in DRGNs. WB showed that Lin28a downregulation reduced Caspase-3/9 proteins and activated TrkA through phosphorylation in BUP-injured DRGNs.

CONCLUSION:

Lin28a is a potent regulator in BUP-induced neuronal apoptosis in DRGNs. The apoptotic protection by Lin28a inhibition is likely through the activation of TrkA signaling pathway.

KEYWORDS:

Apoptosis; Bupivacaine; DRGN; Lin28a; Neuron

PMID:
29245067
DOI:
10.1016/j.biopha.2017.11.142
[Indexed for MEDLINE]

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