Dual effects of heme oxygenase-1 on astrocyte injury induced by hemin in vitro

Brain Inj. 2016;30(1):36-42. doi: 10.3109/02699052.2015.1084648. Epub 2015 Nov 23.

Abstract

Primary objective: The purpose of this study was to investigate the effects of heme oxygenase-1 (HO-1) on astrocyte injury induced by hemin.

Research design: Primary astrocytes were isolated from Sprague Dawley rat pups and cultured in vitro. The expression of HO-1 was induced by hemin in a quantitative fashion and the effects of HO-1 on hemin-induced astrocyte injury were estimated by cell viability, cell membrane permeability and apoptosis.

Methods and procedures: Astrocytes were divided into control group, hemin 5 μM group, hemin 5 μM + Zn-PPIX group, hemin 30 μM group and hemin 30 μM + Zn-PPIX group. Survival quality of astrocyte was measured by WST-8 assay, LDH assay, Hoechst 33258 Staining and annexin V-FITC/PI assay and apoptotic-related proteins were measured using Western blotting.

Main outcome and results: Hemin could dose-dependently up-regulate the expression of HO-1. HO-1 exerted a protective role on astrocyte damage induced by 5 μM hemin, including increased cell survival rate and anti-apoptotic proteins expression (Bcl-2 and p-AKT), as well as decreased LDH release, apoptosis ratio and apoptotic protein expression (Bax, p-ERK and cleaved-caspase3). However, the effect of HO-1 on astrocyte injury between 30 μM hemin-treated groups was opposite of the protective role in 5 μM hemin-treated groups.

Conclusions: There were dual effects of HO-1 in 5 μM and 30 μM hemin-induced astrocyte injuries.

Keywords: Heme oxygenase-1; ZnPP-IX; apoptosis; hemin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Astrocytes / cytology
  • Astrocytes / drug effects*
  • Astrocytes / enzymology*
  • Cell Membrane Permeability / drug effects
  • Cell Survival / drug effects
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Enzyme Induction / drug effects
  • Heme Oxygenase-1 / biosynthesis*
  • Heme Oxygenase-1 / metabolism
  • Hemin / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Up-Regulation / drug effects

Substances

  • Hemin
  • Heme Oxygenase-1