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The Role of Homer1b/c in Neuronal Apoptosis Following LPS-Induced Neuroinflammation

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Abstract

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.

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Acknowledgments

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.

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Authors and Affiliations

  1. Department of Orthopaedics, The Second Affiliated Hospital of Nantong University, Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong, 226002, Jiangsu, People’s Republic of China

    Zhiming Cui, Guanghui Zhu, Xinmin Wu, Yaohua Yan & Xiaopeng Xia

  2. Department of Pharmacology, Pharmacy College, Nantong University, Nantong, 226001, Jiangsu, People’s Republic of China

    Li Zhou

  3. Laboratory animal center, Nantong University, Nantong, 226001, Jiangsu, People’s Republic of China

    Chun Liu

  4. Department of Immunology, Medical College, Nantong University, Nantong, 226001, Jiangsu, People’s Republic of China

    Zhiyun Ben, Yan Song, Ying Zhou & Haiyan Zhang

  5. Department of Pathogen Biology, Medical College, Nantong University, Nantong, 226001, Jiangsu, People’s Republic of China

    Dongmei Zhang

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  1. Zhiming Cui
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  2. Li Zhou
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  3. Chun Liu
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  9. Yan Song
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  10. Ying Zhou
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Correspondence to Dongmei Zhang.

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Zhiming Cui and Li Zhou have contributed equally to this work and shared first author.

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Cui, Z., Zhou, L., Liu, C. et al. The Role of Homer1b/c in Neuronal Apoptosis Following LPS-Induced Neuroinflammation. Neurochem Res 40, 204–215 (2015). https://doi.org/10.1007/s11064-014-1460-6

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  • DOI: https://doi.org/10.1007/s11064-014-1460-6

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