Protective effects of insulin on polychlorinated biphenyls-induced disruption of actin cytoskeleton in hippocampal neurons.
Insulin receptors are widely distributed in the brain, and insulin improves learning and memory in some brain injury. Insulin elevates LIM kinase 1 (LIMK-1) activity and induces actin polymerization in some cells, while actin cytoskeleton dynamics mediated via LIMK-1/cofilin signal pathway is considered important to learning and memory formation. Our previous studies have shown that polychlorinated biphenyls (PCBs) disrupt the actin cytoskeleton by inhibiting LIMK-1/cofilin signaling pathway in the cultured hippocampal neurons. To determine potential neuronal protective effects by insulin, we administered insulin to the cultured hippocampal neurons after exposure to PCBs mixture Aroclor 1254 (A 1254). We found that insulin antagonized a loss of filamentous actin and the cytotoxicity induced by A 1254. Similarly, insulin restored the decrease of LIMK-1 and cofilin phosphorylation induced by A 1254. We concluded that insulin could protect neurons, probably partly by ameliorating filamentous actin cytoskeleton disruption mediated via the activation of LIMK-1/cofilin signal pathway in cultured hippocampal neurons after exposure to A 1254. The above protective effects in hippocampal neuron may have important implications in the treatment of PCBs-induced neurotoxicity and the mechanism by which insulin improves learning and memory. (c) 2007 Wiley Periodicals, Inc. Environ Toxicol 22: 152-158, 2007.
Tang
Feige
F
Shanghai Key Laboratory of Children's Environmental Health, XinHua Hospital, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai 200092, China. tangfeige@163.com
Yan
Chonghuai
C
Li
Fei
F
Wu
Shenghu
S
Yu
Yongguo
Y
Gao
Yu
Y
Jin
Xingming
X
Tian
Ying
Y
Shen
Xiaoming
X
D051339:Actin Depolymerizing Factors / Q000378:metabolism; D000199:Actins / Q000378:metabolism; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D020111:Chlorodiphenyl (54% Chlorine); D003599:Cytoskeleton; D006624:Hippocampus / Q000166:cytology / Q000196:embryology; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology*; D054461:Lim Kinases; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D011494:Protein Kinases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D051339:Actin Depolymerizing Factors; D000199:Actins; D007004:Hypoglycemic Agents; D007328:Insulin; D018696:Neuroprotective Agents; D020111:Chlorodiphenyl (54% Chlorine); D011494:Protein Kinases; D054461:Lim Kinases; C515894:Limk1 protein, rat