PT  - JOURNAL ARTICLE
AU  - Honghong Yao
AU  - Fuwang Peng
AU  - Navneet Dhillon
AU  - Shannon Callen
AU  - Sirosh Bokhari
AU  - Lisa Stehno-Bittel
AU  - S. Omar Ahmad
AU  - John Q. Wang
AU  - Shilpa Buch
TI  - Involvement of TRPC Channels in CCL2-Mediated Neuroprotection against Tat Toxicity
AID  - 10.1523/JNEUROSCI.2781-08.2009
DP  - 2009 Feb 11
TA  - The Journal of Neuroscience
PG  - 1657--1669
VI  - 29
IP  - 6
4099  - http://www.jneurosci.org/content/29/6/1657.short
4100  - http://www.jneurosci.org/content/29/6/1657.full
SO  - J. Neurosci.2009 Feb 11; 29
AB  - 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 κB (NF-κB) 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-κB 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.