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MAPKs and NF‐κB‐mediated acrylamide‐induced neuropathy in rat striatum and human neuroblastoma cells SY5Y
Author(s) -
Yan Dandan,
Pan Xiaoqi,
Yao Jianling,
Wang Dun,
Wu Xu,
Chen Xiaoyi,
Shi Nian,
Yan Hong
Publication year - 2019
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.27671
Subject(s) - tunel assay , apoptosis , p38 mitogen activated protein kinases , proinflammatory cytokine , tumor necrosis factor alpha , kinase , terminal deoxynucleotidyl transferase , tyrosine hydroxylase , endocrinology , nf κb , chemistry , medicine , dopaminergic , biology , protein kinase a , microbiology and biotechnology , biochemistry , dopamine , inflammation
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.