2. Academic Validation
  3. Morphine and Naloxone Facilitate Neural Stem Cells Proliferation via a TET1-Dependent and Receptor-Independent Pathway

Morphine and Naloxone Facilitate Neural Stem Cells Proliferation via a TET1-Dependent and Receptor-Independent Pathway

  • Cell Rep. 2020 Mar 17;30(11):3625-3631.e6. doi: 10.1016/j.celrep.2020.02.075.
Lining Liang 1,  Jinlong Chen 1,  Yuan Li 2,  Xiaowei Lai 1,  Hao Sun 1,  Changpeng Li 2,  Mengdan Zhang 1,  Tingting Yang 1,  Fei Meng 1,  Ping-Yee Law 3,  Horace H Loh 4,  Hui Zheng 5
Affiliations

Affiliations

  • 1 CAS Key Laboratory of Regenerative Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China; Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou 510700, China; Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou 510530, China; University of Chinese Academy of Sciences, Beijing 100049, China.
  • 2 CAS Key Laboratory of Regenerative Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China; Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou 510700, China; Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou 510530, China.
  • 3 Department of Pharmacology, University of Minnesota, Minneapolis, MN 55455, USA.
  • 4 Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou 510700, China; Department of Pharmacology, University of Minnesota, Minneapolis, MN 55455, USA.
  • 5 CAS Key Laboratory of Regenerative Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China; Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou 510700, China; Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou 510530, China; University of Chinese Academy of Sciences, Beijing 100049, China; Institutes for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing 100101, China. Electronic address: zheng_hui@gibh.ac.cn.
PMID: 32187535 DOI: 10.1016/j.celrep.2020.02.075
Abstract

Normally, opioids function in a receptor-dependent manner. They bind to opioid receptors, activate or inhibit receptor activation, and subsequently modulate downstream signal transduction. However, the complex functions of opioids and the low expression of opioid receptors and their endogenous peptide agonists in neural stem cells (NSCs) suggest that some opioids may also modulate NSCs via a receptor-independent pathway. In the current study, two opioids, morphine and naloxone, are demonstrated to facilitate NSC proliferation via a receptor-independent and ten-eleven translocation methylcytosine dioxygenase 1 (TET1)-dependent pathway. Morphine and naloxone penetrate cell membrane, bind to TET1 protein via three key residues (1,880-1,882), and subsequently result in facilitated proliferation of NSCs. In addition, the two opioids also inhibit the DNA demethylation ability of TET1. In summary, the current results connect opioids and DNA demethylation directly at least in NSCs and extend our understanding on both opioids and NSCs.

Keywords

Tet1; morphine; naloxone; neural stem cells; proliferation; receptor-independent.

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