Hyperthermia conditioned astrocyte-cultured medium protects neurons from ischemic injury by the up-regulation of HIF-1 alpha and the increased anti-apoptotic ability.

It has been demonstrated that conditioned medium from astrocytes challenged by in vitro ischemia (oxygen-glucose deprivation, OGD) improved neuronal survival. In addition, preconditioning stimuli can be cross-tolerant, safeguarding against other types of injury. We therefore hypothesized that hyperthermia-conditioned astrocyte-cultured medium (ACM) might also have protective effect on neurons against ischemic injury. The cultured-media, named 38ACM and 40ACM respectively, were collected after astrocytes had been incubated at 38 °C or 40 °C for 6h, followed by incubation at 37 °C for 24h. It was found that ischemia for 6h induced a significant reduction in the number of neuronal cells and cell-viability, and an increase in lactate dehydrogenase (LDH) release and the percentage of apoptotic nuclei in neurons. Pre-treatment with 38ACM or 40ACM for 24h significantly diminished ischemia injury, enhanced cell viability, reduced LDH release and reversed apoptosis. Western blot analysis showed that treatment with 38ACM or 40ACM for 24h led to a significant increase in hypoxia-inducible factor-1 (HIF-1) alpha expression. The EMSA demonstrated that the ACM increased the binding activity of HIF-1 in ischemic neurons. The data implied that hyperthermia-conditioned ACM protects neurons from ischemic injury by up-regulating HIF-1 alpha, and the increased binding activity of HIF-1 and anti-apoptotic ability.
AuthorsFang Du, Xiao Mei Wu, Qi Gong, Xuan He, Ya Ke
JournalEuropean journal of pharmacology (Eur J Pharmacol) Vol. 666 Issue 1-3 Pg. 19-25 (Sep 2011) ISSN: 1879-0712 [Electronic] Netherlands
PMID21620821 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2011 Elsevier B.V. All rights reserved.
Chemical References
  • Culture Media, Conditioned
  • Hif1a protein, mouse
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Erythropoietin
  • L-Lactate Dehydrogenase
  • Animals
  • Apoptosis (drug effects)
  • Astrocytes (cytology)
  • Brain Ischemia (metabolism, pathology)
  • Cell Hypoxia (genetics)
  • Cell Survival (drug effects)
  • Culture Media, Conditioned (pharmacology)
  • Erythropoietin (genetics, metabolism)
  • Hyperthermia, Induced
  • Hypoxia-Inducible Factor 1, alpha Subunit (metabolism)
  • Ischemic Preconditioning
  • L-Lactate Dehydrogenase (metabolism)
  • Mice
  • Neurons (drug effects, enzymology, metabolism, pathology)
  • Response Elements (genetics)
  • Up-Regulation (drug effects)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research network!

Choose Username:
Verify Password: