PMID- 21620821 OWN - NLM STAT- MEDLINE DCOM- 20111025 LR - 20110704 IS - 1879-0712 (Electronic) IS - 0014-2999 (Linking) VI - 666 IP - 1-3 DP - 2011 Sep TI - Hyperthermia conditioned astrocyte-cultured medium protects neurons from ischemic injury by the up-regulation of HIF-1 alpha and the increased anti-apoptotic ability. PG - 19-25 LID - 10.1016/j.ejphar.2011.05.018 [doi] AB - 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 degrees C or 40 degrees C for 6h, followed by incubation at 37 degrees 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. CI - Copyright (c) 2011 Elsevier B.V. All rights reserved. FAU - Du, Fang AU - Du F AD - School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, NT, Hong Kong. FAU - Wu, Xiao Mei AU - Wu XM FAU - Gong, Qi AU - Gong Q FAU - He, Xuan AU - He X FAU - Ke, Ya AU - Ke Y LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20110523 PL - Netherlands TA - Eur J Pharmacol JT - European journal of pharmacology JID - 1254354 RN - 0 (Culture Media, Conditioned) RN - 0 (Hif1a protein, mouse) RN - 0 (Hypoxia-Inducible Factor 1, alpha Subunit) RN - 11096-26-7 (Erythropoietin) RN - EC 1.1.1.27 (L-Lactate Dehydrogenase) SB - IM MH - Animals MH - Apoptosis/*drug effects MH - Astrocytes/*cytology MH - Brain Ischemia/metabolism/*pathology MH - Cell Hypoxia/genetics MH - Cell Survival/drug effects MH - Culture Media, Conditioned/pharmacology MH - Erythropoietin/genetics/metabolism MH - *Hyperthermia, Induced MH - Hypoxia-Inducible Factor 1, alpha Subunit/*metabolism MH - Ischemic Preconditioning MH - L-Lactate Dehydrogenase/metabolism MH - Mice MH - Neurons/*drug effects/enzymology/metabolism/pathology MH - Response Elements/genetics MH - Up-Regulation/*drug effects EDAT- 2011/05/31 06:00 MHDA- 2011/10/26 06:00 CRDT- 2011/05/31 06:00 PHST- 2010/12/27 00:00 [received] PHST- 2011/04/20 00:00 [revised] PHST- 2011/05/03 00:00 [accepted] PHST- 2011/05/31 06:00 [entrez] PHST- 2011/05/31 06:00 [pubmed] PHST- 2011/10/26 06:00 [medline] AID - S0014-2999(11)00548-6 [pii] AID - 10.1016/j.ejphar.2011.05.018 [doi] PST - ppublish SO - Eur J Pharmacol. 2011 Sep;666(1-3):19-25. doi: 10.1016/j.ejphar.2011.05.018. Epub 2011 May 23.