title: Extracellular α-crystallin protects astrocytes from cell death through activation of MAPK, PI3K/Akt signaling pathway and blockade of ROS release from mitochondria.
abstract: α-Crystallin with two isoforms, αA-crystallin (HSPB4) and αB-crystallin (HSPB5), is found in eye lens, spleen, lung, kidney, cornea, skin, but also in brain. Several studies revealed roles of αA/αB-crystallin in regulating cell viability and protection in the central nervous system. We previously demonstrated that α-crystallin serves as an intracellular protectant in astrocytes. Compared to well-studied intracellular functions of α-crystallin, there is limited proof for the role of α-crystallin as extracellular protectant. In order to clarify protective effects of extracellular αA/αB-crystallin, we exposed astrocytes to the toxic agents, staurosporine or C2-ceramide, or serum-starvation in the presence of αA/αB-crystallin. Extracellular αA/αB-crystallin protected astrocytes from staurosporine- and C2-ceramide-induced cell death. In addition, extracellular αB-crystallin/HSPB5 effectively promoted astrocytes viability through phosphatidylinositol 3 kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) and extracellular signal-regulated kinase 1/2 (ERK1/2), p38 mitogen-activated protein kinases (p38) and c-Jun N-terminal kinases (JNK) signaling pathways under serum-deprivation. Furthermore, αB-crystallin/HSPB5 decreases the staurosporine-mediated cleavage of caspase 3 through PI3K/Akt signaling preventing apoptosis of astrocytes. Thus, the current study indicates that extracellular αA/αB-crystallin protects astrocytes exposed to various harmful stimuli. Furthermore, application of αB-crystallin/HSPB5 to isolated rat brain mitochondria inhibits ROS generation induced by complex III inhibition with Antimycin A.
authors.affiliation: Institut für Neurobiochemie (Institut für Inflammation und Neurodegeneration), Otto-von-Guericke-Universität Magdeburg, Medizinische Fakultät, Leipziger Straße 44, Magdeburg 39120, Germany.
authors.forename: Zhihui
authors.initials: Z
authors.lastname: Zhu
authors.affiliation: Institut für Neurobiochemie (Institut für Inflammation und Neurodegeneration), Otto-von-Guericke-Universität Magdeburg, Medizinische Fakultät, Leipziger Straße 44, Magdeburg 39120, Germany.
authors.forename: Rongyu
authors.initials: R
authors.lastname: Li
authors.affiliation: Institut für Neurobiochemie (Institut für Inflammation und Neurodegeneration), Otto-von-Guericke-Universität Magdeburg, Medizinische Fakultät, Leipziger Straße 44, Magdeburg 39120, Germany.
authors.forename: Rolf
authors.initials: R
authors.lastname: Stricker
authors.affiliation: Institut für Neurobiochemie (Institut für Inflammation und Neurodegeneration), Otto-von-Guericke-Universität Magdeburg, Medizinische Fakultät, Leipziger Straße 44, Magdeburg 39120, Germany. Electronic address: georg.reiser@med.ovgu.de.
authors.forename: Georg
authors.initials: G
authors.lastname: Reiser
mesh_terms: D000818:Animals; D000968:Antimycin A / Q000378:metabolism; D001253:Astrocytes / Q000502:physiology*; D001921:Brain / Q000187:drug effects / Q000502:physiology; D016923:Cell Death / Q000187:drug effects / Q000502:physiology*; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004926:Escherichia coli; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000502:physiology; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D013110:Sphingosine / Q000031:analogs & derivatives / Q000633:toxicity; D019311:Staurosporine / Q000633:toxicity; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D038201:alpha-Crystallins / Q000008:administration & dosage / Q000378:metabolism*
chemical_list: D000968:Antimycin A; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D017382:Reactive Oxygen Species; D013110:Sphingosine; D019311:Staurosporine; D058570:TOR Serine-Threonine Kinases; D038201:alpha-Crystallins; C064769:N-acetylsphingosine; C546845:mTOR protein, rat
keywords: Apoptosis; Astrocytes; Neuroprotection; Reactive oxygen species; Small heat shock proteins HSPB4 and HSPB5; α-Crystallin