title: Stress-induced neuroprotective effects of epiregulin and amphiregulin.
abstract: Members of the epidermal growth factor family play important roles in the regulation of cell growth, proliferation, and survival. However, the specific roles of each epidermal growth factor family member with respect to brain injury are not well understood. Gene chip assay screens have revealed drastic increases in the expression of the epidermal growth factor family members amphiregulin and epiregulin following lipopolysaccharide stimulation, which activates an immune response. Both immune activity and endoplasmic reticulum stress are activated during cerebral ischemia. We found that the expression levels of amphiregulin and epiregulin were significantly increased under conditions of cerebral ischemia. Because endoplasmic reticulum stress increased the expression of amphiregulin and epiregulin in glial cells, endoplasmic reticulum stress may be a key mediatory factor of pathophysiological activity. Recombinant epiregulin and amphiregulin proteins effectively inhibited endoplasmic reticulum stress and the subsequent induction of neuronal cell death. Therefore, the upregulation of the epidermal growth factor family members epiregulin and amphiregulin may play a critical role in preventing endoplasmic reticulum stress-induced cell death, thus providing a potential therapy for brain injury.
authors: Department of Traditional Chinese Medicine, The Second Affiliated Hospital, Dalian Medical University, Dalian, China; Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan; College (Institute) of Integrative Medicine, Dalian Medical University, Dalian, China.
authors: Libin
authors: L
authors: Zhan
authors: College (Institute) of Integrative Medicine, Dalian Medical University, Dalian, China.
authors: Luping
authors: L
authors: Zheng
authors: Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan; Department of Pharmacotherapy, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
authors: Toru
authors: T
authors: Hosoi
authors: Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan; Department of Pharmacology, Faculty of Pharmaceutical Sciences, Chiba Institute of Sciences, Choshi, Japan.
authors: Yasunobu
authors: Y
authors: Okuma
authors: Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan; Department of Pharmacology, Kurume University School of Medicine, Kurume, Fukuoka, Japan.
authors: Yasuyuki
authors: Y
authors: Nomura
mesh_terms: D066258:Amphiregulin / Q000235:genetics* / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects / Q000235:genetics; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D059865:Endoplasmic Reticulum Stress / Q000235:genetics; D066260:Epiregulin / Q000235:genetics* / Q000494:pharmacology; D015870:Gene Expression; D000860:Hypoxia / Q000235:genetics / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D007511:Ischemia / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology / Q000494:pharmacology; D051379:Mice; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D013312:Stress, Physiological / Q000187:drug effects* / Q000235:genetics*
chemical_list: D066258:Amphiregulin; D016207:Cytokines; D066260:Epiregulin; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D018696:Neuroprotective Agents; D012333:RNA, Messenger