title: Protective effect of lithium chloride against hypoglycemia-induced apoptosis in neuronal PC12 cell.
abstract: Hypoglycemia is defined by an arbitrary plasma glucose level lower than 3.9mmol/L and is a most common and feared adverse effect of treatment of diabetes mellitus. Emerging evidences demonstrated that hypoglycemia could induce enhanced apoptosis. Lithium chloride (LiCl), a FDA approved drug clinically used for treatment of bipolar disorders, is recently proven having neuroprotection against various stresses in the cellular and animal models of neural disorders. Here, we have established a hypoglycemia model in vitro and assessed the neuroprotective efficacy of LiCl against hypoglycemia-induced apoptosis and the underlying cellular and molecular mechanisms. Our studies showed that LiCl protects against hypoglycemia-induced neurotoxicity in vitro. Exposure to hypoglycemia results in enhanced apoptosis and the underlying cellular and molecular mechanisms involved inhibition of the canonical Wnt signaling pathway by decreasing wnt3a levels, β-catenin levels and increasing GSK-3β levels, which was confirmed by the use of Wnt-specific activator LiCl. Hypoglycemia-induced apoptosis were significantly reversed by LiCl, leading to increased cell survival. LiCl also alters the expression/levels of the Wnt pathway genes/proteins, which were reduced due to exposed to hypoglycemia. Overall, our results conclude that LiCl provides neuroprotection against hypoglycemia-induced apoptosis via activation of the canonical Wnt signaling pathway.
authors.affiliation: Department of Neurology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
authors.forename: Yuzhen
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Central Laboratory, The Central Hospital of Tai'an, Taishan Medical College, Tai'an, Shandong Province, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Wang
authors.affiliation: School of Pharmacy, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Dongsheng
authors.initials: D
authors.lastname: Li
authors.affiliation: School of Pharmacy, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Zhenghua
authors.initials: Z
authors.lastname: Wu
authors.affiliation: School of Pharmacy, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Dawei
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Neurology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
authors.forename: Kaili
authors.initials: K
authors.lastname: Lu
authors.affiliation: Department of Neurology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China. Electronic address: zhao_yuwu2005@126.com.
authors.forename: Yuwu
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Traditional Chinese Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
authors.forename: Yongning
authors.initials: Y
authors.lastname: Sun
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004353:Drug Evaluation, Preclinical; D005434:Flow Cytometry; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D007003:Hypoglycemia / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D045022:Lactate Dehydrogenases / Q000378:metabolism; D018021:Lithium Chloride / Q000494:pharmacology*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D016716:PC12 Cells; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction; D060449:Wnt Signaling Pathway / Q000187:drug effects / Q000502:physiology
chemical_list: D018696:Neuroprotective Agents; D045022:Lactate Dehydrogenases; C505410:Casp3 protein, rat; D053148:Caspase 3; D018021:Lithium Chloride
keywords: apoptosis; hypoglycemia; lithium chloride; wnt signaling pathway