title: Nod-like receptor protein 1 inflammasome mediates neuron injury under high glucose.
abstract: Diabetic encephalopathy is one of the most common complications of diabetes. Inflammatory events during diabetes may be an important mechanism of diabetic encephalopathy. Inflammasome is a multiprotein complex consisting of Nod-like receptor proteins (NLRPs), apoptosis-associated speck-like protein (ASC), and caspase 1 or 5, which functions to switch on the inflammatory process and the release of inflammatory factors. The present study hypothesized that the formation and activation of NLRP1 inflammasome turns on neuroinflammation and neuron injury during hyperglycemia. The results demonstrated that the levels of interleukin-1 beta (IL-1β) were increased in the cortex of streptozocin (STZ)-induced diabetic rats. The levels of mature IL-1β and IL-18 were also elevated in culture medium of neurons treated with high glucose (50 mM). The expression of three essential components of the NLRP1 inflammasome complex, namely, NLRP1, ASC, and caspase 1, was also upregulated in vivo and in vitro under high glucose. Silencing the ASC gene prevented the caspase-1 activation, and inhibiting caspase 1 activity blocked hyperglycemia-induced release of inflammatory factors and neuron injury. Moreover, we found that pannexin 1 mediated the actvitation of NLRP1 inflammasome under high glucose. These results suggest that hyperglycemia induces neuroinflammation through activation of NLRP1 inflammasome, which represents a novel mechanism of diabetes-associated neuron injury.
authors.affiliation: Department of Neurobiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Xian-Fang
authors.initials: XF
authors.lastname: Meng
authors.forename: Xiao-Lan
authors.initials: XL
authors.lastname: Wang
authors.forename: Xiu-Juan
authors.initials: XJ
authors.lastname: Tian
authors.forename: Zhi-Hua
authors.initials: ZH
authors.lastname: Yang
authors.forename: Guang-Pin
authors.initials: GP
authors.lastname: Chu
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.forename: Man
authors.initials: M
authors.lastname: Li
authors.forename: Jing
authors.initials: J
authors.lastname: Shi
authors.forename: Chun
authors.initials: C
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000008:administration & dosage / Q000633:toxicity*; D058847:Inflammasomes / Q000096:biosynthesis*; D009419:Nerve Tissue Proteins / Q000096:biosynthesis*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D058847:Inflammasomes; D009419:Nerve Tissue Proteins; C526260:Nlrp1a protein, rat; D005947:Glucose