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  2. MAPKs and NF-κB-mediated acrylamide-induced neuropathy in rat striatum and human neuroblastoma cells SY5Y

MAPKs and NF-κB-mediated acrylamide-induced neuropathy in rat striatum and human neuroblastoma cells SY5Y

  • J Cell Biochem. 2019 Mar;120(3):3898-3910. doi: 10.1002/jcb.27671.
Dandan Yan 1 Xiaoqi Pan 2 Jianling Yao 1 Dun Wang 3 Xu Wu 1 Xiaoyi Chen 4 Nian Shi 1 Hong Yan 1
Affiliations

Affiliations

  • 1 Department of Health Toxicology, MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • 2 Department of Preventive Medicine, School of Public Health, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
  • 3 Department of Community Health Service Management Center, The Third Affiliated Hospital of Shenzhen University, Shenzhen, China.
  • 4 Department of Nutrition and Food Hygiene, School of Public Health, Guangzhou Medical University, Guangzhou, China.
Abstract

Acrylamide (ACR) is a potent neurotoxin that can be produced during high-temperature food processing, but the underlying toxicological mechanism remains unclear. In this study, the detrimental effects of ACR on the striatal dopaminergic neurons and the roles of mitogen-activated protein kinases (MAPKs) and nuclear factor κB (NF-κB) in ACR-induced neuronal Apoptosis were investigated. Acute ACR exposure caused dopaminergic neurons loss and Apoptosis as revealed by decreased tyrosine hydroxylase (TH)-positive cells and TH protein level and increased terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL)-positive cells in the striatum. ACR-decreased glutathione content, increased levels of malondialdehyde, proinflammatory cytokines tumor necrosis factor α, and interleukin 6. In addition, nuclear NF-κB and MAPKs signaling pathway with c-Jun N-terminal kinase (JNK) and p38 were activated by ACR. Specific inhibitors were used to explore the roles of MAPKs and NF-κB pathways in ACR-induced Apoptosis in SH-SY5Y cells. Pretreatment with JNK-specific inhibitors SP600125 markedly upregulated the reduced B-cell lymphoma 2 (Bcl-2) content and downregulated the increased Bcl-2-associated X protein (Bax) level and thereby eventually reduced the proportions of early and late apoptotic cells induced by ACR, while p38 suppression by SB202190 only reversed the decrease in Bcl-2 expression. Inhibition of NF-κB by BAY 11-7082 markedly upregulated Bax level and decreased Bcl-2 expression, and eventually increasing the proportions of neuronal Apoptosis compared with that in ACR alone. These results suggested that JNK contributed to ACR-induced Apoptosis, while NF-κB acted as a protective regulator in response to ACR-induced neuropathy. This study helps to offer a deeper insight into the mechanism of ACR-induced neuropathy.

Keywords

acrylamide; apoptosis; inflammation; mitogen-activated protein kinases; nuclear factor kappa B.

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