The Multi-target Mechanism of CCL2/CCR2 Involved in Neuropathic Pain

doi:10.3969/j.issn.2095-1396.2016.01.007

Abstract

Abstract: CCL2 is the first discovered human CC chemokine and a potent chemotactic factor for monocytes，which induces immunological and inflammatory response. CCL2 and its receptor CCR2 play a key role in development and maintainence of neuropathic pain. Study found that CCL2 can be produced by neurons，and CCL2 acts as a neuromodulator in the process of pain disorder. CCL2 is the common mediator of neuropathic pain，immunological and inflammatory response. CCL2 involves in neuropathic pain at different levels，including peripheral sensory afferent nerve，dorsal root ganglia and spinal cord，which facilitates pain transmission. CCL2/CCR2 regulates neuropathic pain based on the following mechanisms：①enhances current amplitude and levels of TRPV1 mRNA by upregulating PI3K/Akt pathway，②CCL2 selectively increases mRNA of Nav1.8 through activating PI3K/Akt pathway and enhancing amplitude of TTX-R current，③significantly decreases voltage dependent noninactivation potassium current （IK） in DRG neurons，and has different effects on potassium channel in DRG neurons from different NP animal models，④enhances NMDA and AMPA evoked currents in spinal cord neurons，and enhances their spontaneous excitatory postsynaptic currents （EPSCs），⑤there is a bidirectional regulation between opioid receptors and CCL2/CCR2，⑥CCL2 directly inhibits GABA current in neurons.

Key words: monocyte chemoattractant protein-1（CCL2), C-C chemokine receptor type2(CCR2), neuropathic pain, ion channel, receptor

CLC Number:

R965

LI Li，ZHANG Hai-lin. The Multi-target Mechanism of CCL2/CCR2 Involved in Neuropathic Pain[J]. Acta Neuropharmacologica, 2016, 6(1): 49-57.

References

[1] Ana Clara Cristovao, Dong-Hee Choi, Graca Baltazar, et al. The role of NADPH oxidase 1-derived reactive oxygen species in paraquat-mediated dopaminergic cell death[J]. Antioxid Redox Signal, 2009, 11(9): 2105-2118.

[2] Johanna Mäkelä, Timofey V Tselykh, Jyrki P Kukkonen, et al. Peroxisome proliferator-activated receptor-γ (PPARγ) agonist is neuroprotective and stimulates PGC-1α expression and CREB phosphorylation in human dopaminergic neurons[J]. Neuropharmacology, 2016, 102: 266-275.

[3] Nirit Lev, Yael Barhum, Neri S Pilosof, et al. DJ-1 protects against dopamine toxicity: implications for Parkinson's disease and aging[J]. J Gerontol A Biol Sci Med Sci, 2013, 68(3): 215-225.

[4] Alvin P Joselin, Sarah J Hewitt, Steve M Callagham, et al. ROS-dependent regulation of Parkin and DJ-1 localization during oxidative stress in neurons[J]. Hum Mol Genet, 2012, 21(22): 4888-4903.

[5] Kazuki Hattori, Isao Naguro, Christopher Runchel, et al. The roles of ASK family proteins in stress responses and diseases[J]. Cell Commun Signal, 2009, 7: 9.

[6] Jens Waak, Stephanie Weber, Karin Gorner, et al. Oxidizable residues mediating protein stability and cytoprotective interaction of DJ-1 with apoptosis signal-regulating kinase 1[J]. J Biol Chem, 2009, 284(21): 14245-57.

[7] Xiao Tao, Liang Tong. Crystal structure of human DJ-1, a protein associated with early onset Parkinson's disease[J]. J Biol Chem, 2003, 278(33): 31372-31379.

[8] Olga Corti, Suzanne Lesage, Alexis Brice. What genetics tells us about the causes and mechanisms of Parkinson's disease[J]. Physiol Rev, 2011, 91(4): 1161-1218.

[9] Hiromasa Ooe, Chinatsu Maita, Hiroshi Maita, et al. Specific cleavage of DJ-1 under an oxidative condition[J]. Neurosci Lett, 2006, 406(3): 165-168.

[10] Chen Jue, Li Lian, Chin Lih-shen. Parkinson disease protein DJ-1 converts from a zymogen to a protease by carboxyl-terminal cleavage[J]. Hum Mol Genet, 2010, 19(12): 2395-2408.

[11] N Kotaria, U Hinz, S Zechel, et al. Localization of DJ-1 protein in the murine brain[J]. Cell Tissue Res, 2005, 322(3): 503-507.

[12] Junn Eunsung, Won Hee Jang, Zhao-xin, et al. Mitochondrial localization of DJ-1 leads to enhanced neuroprotection[J]. J Neurosci Res, 2009, 87(1): 123-129.

[13] V Bonifati, P Rizzu, F Squitieri, et al. DJ-1( PARK7), a novel gene for autosomal recessive, early onset parkinsonism[J]. Neurol Sci, 2003, 24(3): 159-160.

[14] Vincenzo Bonifati, Patrizia Rizzu, Marijke J Van Baren, et al. Mutations in the DJ-1 gene associated with autosomal recessive early-onset parkinsonism[J]. Science, 2003, 299(5604): 256-259.

[15] Joungil Choi, M Cameron Sullards, James A Olzmann, et al. Oxidative damage of DJ-1 is linked to sporadic Parkinson and Alzheimer diseases[J]. J Biol Chem, 2006, 281(16): 10816-10824.

[16] Dong Hwan Ho, Sanghak Yi, Hyemyung Seo, et al. Increased DJ-1 in urine exosome of Korean males with Parkinson's disease[J]. Biomed Res Int, 2014, 2014:704678.

[17] Kang Wen-yan, Yang Qiong, Jiang Xu-feng, et al. Salivary DJ-1 could be an indicator of Parkinson's disease progression[J]. Front Aging Neurosci, 2014, 6: 102.

[18] Masaaki Waragai, Masaaki Nakai, Jianshe Wei, et al. Plasma levels of DJ-1 as a possible marker for progression of sporadic Parkinson's disease[J]. Neurosci Lett, 2007, 425(1): 18-22.

[19] Yoshiro Saito. Oxidized DJ-1 as a possible biomarker of Parkinson's disease[J]. J Clin Biochem Nutr, 2014, 54(3): 138-144.

[20] W Davis Parker, Janice K Parks, Russell H Swerdlow. Complex I deficiency in Parkinson's disease frontal cortex[J]. Brain Res, 2008, 1189: 215-218.

[21] C W Olanow. The pathogenesis of cell death in Parkinson's disease--2007[J]. Mov Disord, 2007, 22(Suppl 17): S335-S342.

[22] P Jenner. Oxidative stress in Parkinson's disease and other neurodegenerative disorders[J]. Pathol Biol (Paris), 1996, 44(1): 57-64.

[23] Philipp J Kahle, Jens Waak, Thomas Gasser. DJ-1 and prevention of oxidative stress in Parkinson's disease and other age-related disorders[J]. Free Radic Biol Med, 2009, 47(10): 1354-1361.

[24] Hiroyoshi Ariga, Kazuko Takahashi, Izumi Kato, et al. Neuroprotective function of DJ-1 in Parkinson's disease[J]. Oxid Med Cell Longev, 2013, 2013: 683920.

[25] Rosa M Canet-Aviles, Mark A Wilson, David W Miller, et al. The Parkinson's disease protein DJ-1 is neuroprotective due to cysteine-sulfinic acid-driven mitochondrial localization[J]. Proc Natl Acad Sci USA, 2004, 101(24):9103-9108.

[26] Eunsung Junn, Hiroyuki Taniguchi, Byeong Seon Jeong, et al. Interaction of DJ-1 with Daxx inhibits apoptosis signal-regulating kinase 1 activity and cell death[J]. Proc Natl Acad Sci USA, 2005, 102(27): 9691-9696.

[27] Liu Fang, Jamie L Nguyen, John D Hulleman, et al. Mechanisms of DJ-1 neuroprotection in a cellular model of Parkinson's disease[J]. J Neurochem, 2008, 105(6): 2435-53.

[28] Zhou Wen-bo, Curt R Freed. DJ-1 up-regulates glutathione synthesis during oxidative stress and inhibits A53T alpha-synuclein toxicity[J]. J Biol Chem, 2005, 280(52): 43150-43158.

[29] Derek A Drechsel, Manisha Patel. Respiration-dependent H2O2 removal in brain mitochondria via the thioredoxin/peroxiredoxin system[J]. J Biol Chem, 2010, 285(36): 27850-27858.

[30] Pamela Lopert, Manisha Patel. Brain mitochondria from DJ-1 knockout mice show increased respiration-dependent hydrogen peroxide consumption[J]. Redox Biology, 2014, 2:667-672.

[31] Casey M Clements, Richard S McNally, Brian J Conti, et al. DJ-1, a cancer- and Parkinson's disease-associated protein, stabilizes the antioxidant transcriptional master regulator Nrf2[J]. Proc Natl Acad Sci USA, 2006, 103(41):15091-15096.

[32] Melba C Jaramillo, Donna D Zhang. The emerging role of the Nrf2-Keap1 signaling pathway in cancer[J]. Genes Dev, 2013, 27(20): 2179-2191.

[33] Li Gan, Delinda A Johnson, Jeffrey A Johnson. Keap1-Nrf2 activation in the presence and absence of DJ-1[J]. Eur J Neurosci, 2010, 31(6): 967-977.

[34] Tatsuki Yasuda, Yusuke Kaji, Tomohiro, et al. DJ-1 cooperates with PYCR1 in cell protection against oxidative stress[J]. Biochem Biophys Res Commun, 2013, 436(2):289-294.

[35] David Seo, Goldschmidt-Clemont P. The paraoxonase gene family and atherosclerosis[J]. Free Radic Biol Med, 2005, 38(2):153-163.

[36] Lucio G Costa, Rian de Laat, Khoi Dao, et al. Paraoxonase-2 (PON2) in brain and its potential role in neuroprotection[J]. Neurotoxicology, 2014, 43: 3-9.

[37] Jagan Mohan Jasna, Kannadasan Anandbabu, Subramaniam Rajesh Bharathi, et al. Paraoxonase enzyme protects retinal pigment epithelium from chlorpyrifos insult[J]. PLoS One, 2014, 9(6):e101380.

[38] Mohammad Parsanejad, Noam Bourquard, Dianbo Qu, et al. DJ-1 interacts with and regulates paraoxonase-2, an enzyme critical for neuronal survival in response to oxidative stress[J]. PLoS One, 2014, 9(9): e106601.

[39] Rob M Ewing, Peter Chu, Fred Elisma, et al. Large-scale mapping of human protein-protein interactions by mass spectrometry[J]. Mol Syst Biol, 2007, 3(1):89.

[40] M D P Willcox, M Parsanejad, D W S Harty, et al. Regulation of the VHL/HIF-1 pathway by DJ-1[J]. J Neurosci, 2014, 34(23): 8043-8050.

[41] Xiong Ran, Wang Zhi-quan, Zhao Zong-bo, et al. MicroRNA-494 reduces DJ-1 expression and exacerbates neurodegeneration[J]. Neurobiol Aging, 2014, 35(3): 705-714.