Evidence that intracellular cyclophilin A and cyclophilin A/CD147 receptor-mediated ERK1/2 signalling can protect neurons against in vitro oxidative and ischemic injury

Sherif Boulos, Bruno Meloni, Peter Arthur, Bernadette Majda, Christina Bojarski, Neville Knuckey

Research output: Contribution to journalArticle

86 Citations (Scopus)

Abstract

We previously reported that cyclophilin A protein is up-regulated in cortical neuronal cultures following several preconditioning treatments. In the present study, we have demonstrated that adenoviral-mediated over-expression of cyclophilin A in rat cortical neuronal cultures can protect neurons from oxidative stress (induced by cumene hydroperoxide) and in vitro ischemia (induced by oxygen glucose deprivation). We subsequently demonstrated that cultured neurons, but not astrocytes, express the recently identified putative cyclophilin A receptor, CD147 (also called neurothelin, basigin and EMMPRIN), and that administration of purified cyclophilin A protein to neuronal cultures induces a rapid but transient phosphorylation of the extracellular signal-regulated kinase (ERK) 1/2. Furthermore, administration of purified cyclophilin A protein to neuronal cultures protects neurons from oxidative stress and in vitro ischemia. Interestingly, we detected up-regulation of cyclophilin A mRNA, but not protein in the hippocampus following a 3-min period of sublethal global cerebral ischemia in the rat. Despite our in vivo findings, our in vitro data show that cyclophilin A has both intracellular- and extracellular-mediated neuroprotective mechanisms. To this end, we propose cyclophilin A's extracellular-mediated neuroprotection occurs via CD147 receptor signalling, possibly by activation of ERK1/2 pro-survival pathways. Further characterization of cyclophilin A's neuroprotective mechanisms may aid the development of a neuroprotective therapy. (c) 2006 Elsevier Inc. All rights reserved.
Original languageEnglish
Pages (from-to)54-64
JournalNeurobiology of Disease
Volume25
Issue number1
DOIs
Publication statusPublished - 2007

Fingerprint

Cyclophilin A
Neurons
Wounds and Injuries
Cyclophilins
Proteins
Oxidative Stress
CD147 Antigens
Ischemia
Mitogen-Activated Protein Kinase 3
Mitogen-Activated Protein Kinase 1
In Vitro Techniques
Brain Ischemia
Astrocytes
Hippocampus
Up-Regulation
Phosphorylation
Oxygen
Glucose
Messenger RNA

Cite this

@article{c13ef7c409ac41d6ade88d6bd936e4d5,
title = "Evidence that intracellular cyclophilin A and cyclophilin A/CD147 receptor-mediated ERK1/2 signalling can protect neurons against in vitro oxidative and ischemic injury",
abstract = "We previously reported that cyclophilin A protein is up-regulated in cortical neuronal cultures following several preconditioning treatments. In the present study, we have demonstrated that adenoviral-mediated over-expression of cyclophilin A in rat cortical neuronal cultures can protect neurons from oxidative stress (induced by cumene hydroperoxide) and in vitro ischemia (induced by oxygen glucose deprivation). We subsequently demonstrated that cultured neurons, but not astrocytes, express the recently identified putative cyclophilin A receptor, CD147 (also called neurothelin, basigin and EMMPRIN), and that administration of purified cyclophilin A protein to neuronal cultures induces a rapid but transient phosphorylation of the extracellular signal-regulated kinase (ERK) 1/2. Furthermore, administration of purified cyclophilin A protein to neuronal cultures protects neurons from oxidative stress and in vitro ischemia. Interestingly, we detected up-regulation of cyclophilin A mRNA, but not protein in the hippocampus following a 3-min period of sublethal global cerebral ischemia in the rat. Despite our in vivo findings, our in vitro data show that cyclophilin A has both intracellular- and extracellular-mediated neuroprotective mechanisms. To this end, we propose cyclophilin A's extracellular-mediated neuroprotection occurs via CD147 receptor signalling, possibly by activation of ERK1/2 pro-survival pathways. Further characterization of cyclophilin A's neuroprotective mechanisms may aid the development of a neuroprotective therapy. (c) 2006 Elsevier Inc. All rights reserved.",
author = "Sherif Boulos and Bruno Meloni and Peter Arthur and Bernadette Majda and Christina Bojarski and Neville Knuckey",
year = "2007",
doi = "10.1016/j.nbd.2006.08.012",
language = "English",
volume = "25",
pages = "54--64",
journal = "Neurobiology of Disease",
issn = "0969-9961",
publisher = "Academic Press",
number = "1",

}

TY - JOUR

T1 - Evidence that intracellular cyclophilin A and cyclophilin A/CD147 receptor-mediated ERK1/2 signalling can protect neurons against in vitro oxidative and ischemic injury

AU - Boulos, Sherif

AU - Meloni, Bruno

AU - Arthur, Peter

AU - Majda, Bernadette

AU - Bojarski, Christina

AU - Knuckey, Neville

PY - 2007

Y1 - 2007

N2 - We previously reported that cyclophilin A protein is up-regulated in cortical neuronal cultures following several preconditioning treatments. In the present study, we have demonstrated that adenoviral-mediated over-expression of cyclophilin A in rat cortical neuronal cultures can protect neurons from oxidative stress (induced by cumene hydroperoxide) and in vitro ischemia (induced by oxygen glucose deprivation). We subsequently demonstrated that cultured neurons, but not astrocytes, express the recently identified putative cyclophilin A receptor, CD147 (also called neurothelin, basigin and EMMPRIN), and that administration of purified cyclophilin A protein to neuronal cultures induces a rapid but transient phosphorylation of the extracellular signal-regulated kinase (ERK) 1/2. Furthermore, administration of purified cyclophilin A protein to neuronal cultures protects neurons from oxidative stress and in vitro ischemia. Interestingly, we detected up-regulation of cyclophilin A mRNA, but not protein in the hippocampus following a 3-min period of sublethal global cerebral ischemia in the rat. Despite our in vivo findings, our in vitro data show that cyclophilin A has both intracellular- and extracellular-mediated neuroprotective mechanisms. To this end, we propose cyclophilin A's extracellular-mediated neuroprotection occurs via CD147 receptor signalling, possibly by activation of ERK1/2 pro-survival pathways. Further characterization of cyclophilin A's neuroprotective mechanisms may aid the development of a neuroprotective therapy. (c) 2006 Elsevier Inc. All rights reserved.

AB - We previously reported that cyclophilin A protein is up-regulated in cortical neuronal cultures following several preconditioning treatments. In the present study, we have demonstrated that adenoviral-mediated over-expression of cyclophilin A in rat cortical neuronal cultures can protect neurons from oxidative stress (induced by cumene hydroperoxide) and in vitro ischemia (induced by oxygen glucose deprivation). We subsequently demonstrated that cultured neurons, but not astrocytes, express the recently identified putative cyclophilin A receptor, CD147 (also called neurothelin, basigin and EMMPRIN), and that administration of purified cyclophilin A protein to neuronal cultures induces a rapid but transient phosphorylation of the extracellular signal-regulated kinase (ERK) 1/2. Furthermore, administration of purified cyclophilin A protein to neuronal cultures protects neurons from oxidative stress and in vitro ischemia. Interestingly, we detected up-regulation of cyclophilin A mRNA, but not protein in the hippocampus following a 3-min period of sublethal global cerebral ischemia in the rat. Despite our in vivo findings, our in vitro data show that cyclophilin A has both intracellular- and extracellular-mediated neuroprotective mechanisms. To this end, we propose cyclophilin A's extracellular-mediated neuroprotection occurs via CD147 receptor signalling, possibly by activation of ERK1/2 pro-survival pathways. Further characterization of cyclophilin A's neuroprotective mechanisms may aid the development of a neuroprotective therapy. (c) 2006 Elsevier Inc. All rights reserved.

U2 - 10.1016/j.nbd.2006.08.012

DO - 10.1016/j.nbd.2006.08.012

M3 - Article

VL - 25

SP - 54

EP - 64

JO - Neurobiology of Disease

JF - Neurobiology of Disease

SN - 0969-9961

IS - 1

ER -