期刊
JOURNAL OF NEUROSCIENCE
卷 29, 期 6, 页码 1657-1669出版社
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.2781-08.2009
关键词
CCL2; TRPC; midbrain neurons; Ca2+; ERK; Akt
资金
- National Institutes of Health [MH62969, RR016443, MH-068212, DA020392, DA024442]
Chemokine (C-C motif) ligand 2 (CCL2), also known as monocyte chemoattractant protein-1, plays a critical role in leukocyte recruitment and activation. In the present study, we identify an additional role for CCL2 that of neuroprotection against HIV-1 transactivator protein ( Tat) toxicity in rat primary midbrain neurons. Furthermore, we report the involvement of transient receptor potential canonical ( TRPC) channels in CCL2-mediated neuroprotection. TRPC are Ca2+-permeable, nonselective cation channels with a variety of physiological functions. Blockage of TRPC channels resulted in suppression of both CCL2-mediated neuroprotection and intracellular Ca2+ elevations. Parallel but distinct extracellular signal-regulated kinase (ERK)/cAMP response element-binding protein ( CREB) and Akt/nuclear factor kappa B (NF-kappa B) pathways were involved in the CCL2-mediated neuroprotection. Blocking TRPC channels and specific downregulation of TRPC channels 1 and 5 resulted in suppression of CCL2-induced ERK/CREB activation but not Akt/NF-kappa B activation. In vivo relevance of these findings was further corroborated in wild-type and CCR2 knock-out mice. In the wild-type but not CCR2 knock-out mice, exogenous CCL2 exerted neuroprotection against intrastriatal injection of HIV-1 Tat. These findings clearly demonstrate a novel role of TRPC channels in the protection of neurons against Tat through the CCL2/CCR2 axis.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据