The effect of propofol on hypoxia-modulated expression of heat shock proteins: potential mechanism in modulating blood-brain barrier permeability.

Abstract

Heat shock proteins (HSPs) may be induced by hypoxia and alleviate blood-brain barrier (BBB) damage. The neuroprotective effect of propofol has been reported. We aimed to identify whether propofol induced HSPs expression and protected BBB integrity. Mouse astrocytes and microglia cells were cultured and exposed to hypoxia and propofol. The expression of HSP27, HSP32, HSP70, and HSP90, and the translocation of heat shock factor 1 (HSF1) and Nuclear factor-E2-related factor 2 (Nrf2) were investigated. Mouse brain microvascular endothelial cells, astrocytes, and microglial cells were co-cultured to establish in vitro BBB model, and the effects of hypoxia and propofol as well as HSPs knockdown/overexpression on BBB integrity were measured. Hypoxia (5% O2, 5% CO2, 90% humidity) treatment for 6 h and 12 h induced HSP27, HSP32, and HSP70 expression. Propofol (25 μΜ) increased HSP27 and HSP32 expression, starting with exposure to hypoxia for 3 h. Propofol induced HSF1 translocation from cytoplasmic to nuclear compartment, and blockade of HSF1 inhibited HSP27 expression in mouse astrocytes when they were exposed to hypoxia for 3 h. Propofol induced Nrf2 translocation, and blockade of Nrf2 inhibited HSP32 expression in mouse microglial cells when they were exposed to hypoxia for 3 h. Propofol protected hypoxia-impaired BBB integrity, and the effects were abolished by blockade of HSF1 and Nrf2. Overexpression of HSP27 and HSP32 alleviated hypoxia-impaired BBB integrity, and blockade of HSP27 and HSP32 expression ameliorated propofol-mediated protection against BBB impairment. Propofol may protect hypoxia-mediated BBB impairment. The mechanisms may involve HSF1-mediated HSP27 expression and Nrf2-mediated HSP32 expression.

• Authors: Xia Sun, YueHao Yin, Lingchao Kong, Wei Chen, Changhong Miao, Jiawei Chen
• Journal: Molecular and cellular biochemistry (Mol Cell Biochem) Vol. 462 Issue 1-2 Pg. 85-96 (Dec 2019) ISSN: 1573-4919 [Electronic] Netherlands
• PMID: 31446614 (Publication Type: Journal Article)

Chemical References

• Heat-Shock Proteins
• NF-E2-Related Factor 2
• Protective Agents
• Propofol

Topics

• Animals
• Blood-Brain Barrier (drug effects, metabolism)
• Cell Hypoxia (drug effects)
• Heat-Shock Proteins (metabolism)
• Mice
• NF-E2-Related Factor 2 (metabolism)
• Permeability
• Propofol (pharmacology)
• Protective Agents (pharmacology)