Involvement of TRPC channels in CCL2-mediated neuroprotection against Tat toxicity

Honghong Yao, Fuwang Peng, Navneet Dhillon, Shannon Callen, Sirosh Bokhari, Lisa Stehno-Bittel, S. Omar Ahmad, John Q. Wang, Shilpa Buch

Research output: Contribution to journalArticle

63 Citations (Scopus)

Abstract

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 Ca 2+-permeable, nonselective cation channels with a variety of physiological functions. Blockage of TRPC channels resulted in suppression of both CCL2-mediated neuroprotection and intracellular Ca 2+ 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.

Original languageEnglish (US)
Pages (from-to)1657-1669
Number of pages13
JournalJournal of Neuroscience
Volume29
Issue number6
DOIs
StatePublished - Feb 11 2009

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Transient Receptor Potential Channels
Trans-Activators
Ligands
Human Immunodeficiency Virus rev Gene Products
Proteins
Cyclic AMP Response Element-Binding Protein
Complement Factor B
Chemokine CCL2
Knockout Mice
HIV-1
Mitogen-Activated Protein Kinase 1
Extracellular Signal-Regulated MAP Kinases
Mesencephalon
Protein C
Neuroprotection
Cations
Leukocytes
Down-Regulation
Neurons
Injections

Keywords

  • Akt
  • CCL2
  • Ca
  • ERK
  • Midbrain neurons
  • TRPC

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Involvement of TRPC channels in CCL2-mediated neuroprotection against Tat toxicity. / Yao, Honghong; Peng, Fuwang; Dhillon, Navneet; Callen, Shannon; Bokhari, Sirosh; Stehno-Bittel, Lisa; Ahmad, S. Omar; Wang, John Q.; Buch, Shilpa.

In: Journal of Neuroscience, Vol. 29, No. 6, 11.02.2009, p. 1657-1669.

Research output: Contribution to journalArticle

Yao, H, Peng, F, Dhillon, N, Callen, S, Bokhari, S, Stehno-Bittel, L, Ahmad, SO, Wang, JQ & Buch, S 2009, 'Involvement of TRPC channels in CCL2-mediated neuroprotection against Tat toxicity', Journal of Neuroscience, vol. 29, no. 6, pp. 1657-1669. https://doi.org/10.1523/JNEUROSCI.2781-08.2009
Yao H, Peng F, Dhillon N, Callen S, Bokhari S, Stehno-Bittel L et al. Involvement of TRPC channels in CCL2-mediated neuroprotection against Tat toxicity. Journal of Neuroscience. 2009 Feb 11;29(6):1657-1669. https://doi.org/10.1523/JNEUROSCI.2781-08.2009
Yao, Honghong ; Peng, Fuwang ; Dhillon, Navneet ; Callen, Shannon ; Bokhari, Sirosh ; Stehno-Bittel, Lisa ; Ahmad, S. Omar ; Wang, John Q. ; Buch, Shilpa. / Involvement of TRPC channels in CCL2-mediated neuroprotection against Tat toxicity. In: Journal of Neuroscience. 2009 ; Vol. 29, No. 6. pp. 1657-1669.
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