Chloroquine inhibits autophagy and deteriorates the mitochondrial dysfunction and apoptosis in hypoxic rat neurons.

Abstract

AIMS:

Mitochondrial dysfunction (MD) and apoptosis in the neurons are associated with neonatal hypoxic-ischemic (HI) encephalopathy (HIE). The present study was to explore the influence of autophagy on the induction of MD and apoptosis in the neurons in a neonatal HIE rats and in hypoxia-treated neurons in vitro.

MATERIALS AND METHODS:

Ten-day-old HI rat pups were sacrificed for brain pathological examination and immunohistochemical analysis. The induction of autophagy, apoptosis and MD were also determined in the neurons under hypoxia, with or without autophagy inhibitor, chloroquine (CQ) treatment.

KEY FINDINGS:

HI treatment caused atrophy and apoptosis of neurons, with a significantly increased levels of apoptosis- and autophagy-associated proteins, such as cleaved caspase 3 and the B subunit of autophagy-related microtubule-associated protein 1 light chain 3 (LC3-B). in vitro experiments demonstrated that the hypoxia induced autophagy in neurons, as was inhibited by CQ. The hypoxia-induced cytochrome c release, cleaved caspase 3 and cleaved caspase 9 were aggravated by CQ. Moreover, there were higher levels of reactive oxygen species, more mitochondrial superoxide and less mitochondrial membrane potential in the CQ-treated neurons under hypoxia than in the neurons singularly under hypoxia.

SIGNIFICANCE:

Apoptosis and autophagy were induced in HI neonatal rat neurons, autophagy inhibition deteriorates the hypoxia-induced neuron MD and apoptosis. It implies a neuroprotection of autophagy in the hypoxic-ischemic encephalopathy. Administration of autophagy inducer agents might be promising in HIE treatment.

• Authors: Peng Li, Lei Hao, Yan-Yan Guo, Guang-Lu Yang, Hua Mei, Xiao-Hua Li, Qiong-Xiang Zhai
• Journal: Life sciences (Life Sci) Vol. 202 Pg. 70-77 (Jun 01 2018) ISSN: 1879-0631 [Electronic] Netherlands
• PMID: 29331314 (Publication Type: Journal Article)
• Copyright: Copyright © 2018. Published by Elsevier Inc.

Chemical References

• LC3 protein, rat
• Microtubule-Associated Proteins
• Neuroprotective Agents
• Reactive Oxygen Species
• Chloroquine

Topics

• Animals
• Apoptosis (drug effects)
• Atrophy
• Autophagy (drug effects)
• Cell Hypoxia (drug effects)
• Chloroquine (pharmacology)
• Hypoxia-Ischemia, Brain (pathology)
• Membrane Potential, Mitochondrial (drug effects)
• Microtubule-Associated Proteins (biosynthesis, genetics)
• Mitochondrial Diseases (chemically induced)
• Neurons (drug effects, pathology)
• Neuroprotective Agents (pharmacology)
• Rats
• Rats, Sprague-Dawley
• Reactive Oxygen Species (metabolism)