The Role of Homer1b/c in Neuronal Apoptosis Following LPS-Induced Neuroinflammation
- 359 Downloads
Homer, also designated Vesl, is one member of the newly found postsynaptic density scaffold proteins, playing a vital role in maintaining synaptic integrity, regulating intracellular calcium mobilization, and being critical for the regulation of cellular apoptosis. However, its function in the inflamed central nervous system (CNS) is not fully elucidated. Here, we investigated the role of Homer1b/c, a long form of Homer1, in lipopolysaccharide (LPS) induced neuroinflammation in CNS. Western blot analysis indicated that LPS administration significantly increased the expression of Homer1b/c in rat brain. Moreover, double immunofluorescent staining suggested Homer1b/c was mainly distributed in the cytoplasm of neurons and had a close association with cleaved caspase-3 level in neurons in rat brain after LPS injection. In vitro studies indicated that up-regulation of Homer1b/c might be related to the subsequent apoptosis in neurons treated by conditioned media (CM), collected from LPS-stimulated mixed glial cultures (MGC). We also found down-regulation of Homer1b/c partly blocked the increase of cleaved caspase-3 and the proportion of Bax/Bcl-2 in neurons induced by MGC-CM. Taken together, these findings suggested that Homer1b/c might promote neuronal apoptosis via the Bax/Bcl-2 dependent pathway during neuroinflammation in CNS, and inhibiting Homer1b/c expression might provide a novel neuroprotective strategy against the inflammation-related neuronal apoptosis.
KeywordsHomer1b/c Neuroinflammation Neuronal apoptosis Lipopolysaccharide Rat
This study was supported by the Nantong City Social Development Projects Funds (HS 2012032) and a project funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD), Nantong University graduate scientific and technological innovation projects (YKC13069).
Conflict of interest
All authors declare that they have no conflicts of interest.
- 8.Gavilan MP, Revilla E, Pintado C, Castano A, Vizuete ML, Moreno-Gonzalez I, Baglietto-Vargas D, Sanchez-Varo R, Vitorica J, Gutierrez A, Ruano D (2007) Molecular and cellular characterization of the age-related neuroinflammatory processes occurring in normal rat hippocampus: potential relation with the loss of somatostatin GABAergic neurons. J Neurochem 103:984–996PubMedCrossRefGoogle Scholar
- 23.Smith TH, Ngwainmbi J, Grider JR, Dewey WL, Akbarali HI (2013) An in vitro preparation of isolated enteric neurons and glia from the myenteric plexus of the adult mouse. J Vis Exp. doi: 10.3791/50688
- 26.McNamee EN, Griffin EW, Ryan KM, Ryan KJ, Heffernan S, Harkin A, Connor TJ (2010) Noradrenaline acting at beta-adrenoceptors induces expression of IL-1beta and its negative regulators IL-1ra and IL-1RII, and drives an overall anti-inflammatory phenotype in rat cortex. Neuropharmacology 59:37–48PubMedCrossRefGoogle Scholar
- 28.Baby N, Patnala R, Ling EA, Dheen ST (2014) Nanomedicine and its application in treatment of microglia-mediated neuroinflammation. Curr Med Chem 21:4215–4226Google Scholar
- 29.Wang SM, Lee YC, Ko CY, Lai MD, Lin DY, Pao PC, Chi JY, Hsiao YW, Liu TL, Wang JM (2014) Increase of zinc finger protein 179 in response to CCAAT/enhancer binding protein delta conferring an antiapoptotic effect in astrocytes of Alzheimer’s disease. Mol Neurobiol. doi: 10.1007/s12035-014-8714-9