This study aimed to analyze the neurological changes induced by acrylamide (ACR) poisoning and their underlying mechanisms within the spinal cords of male adult Wistar rats. The rats were randomly divided into three groups (n = 9 rats per group). ACR was intraperitoneally injected to produce axonopathy according to the daily dosing schedules of 20 or 40 mg/kg/day of ACR for eight continuous weeks (three times per week). During the exposure period, body weights and gait scores were assessed, and the concentration of Ca2+ was calculated in 27 mice. Protein kinase A (PKA), protein kinase C (PKC), cyclin-dependent protein kinase 5 (CDK5), and P35 were assessed by electrophoretic resolution and Western blotting. The contents of 3′-cyclic adenosine monophosphate (cAMP) and calmodulin (CaM) were determined using ELISA kits, and the activities of calcium/calmodulin-dependent protein kinase II (CaMKII), PKA, and PKC were determined using the commercial Signa TECTPKAassay kits. Compared with control rats, treatment with 20 and 40 mg/kg of ACR decreased body weight and increased gait scores at 8 weeks. Intracellular Ca2+ levels increased significantly in treated rats; CaM, PKC, CDK5, and P35 levels were significantly decreased; and PKA and cAMP levels remained unchanged. CaMKII, PKA, and PKC activities increased significantly. The results indicated that ACR can damage neurofilaments by affecting the contents and activities of CaM, CaMKII, PKA, cAMP, PKC, CDK5, and P35, which could result in ACR toxic neuropathy.
AhmedHHElmegeedaGAAbd-ElhalimMM, et al. (2010)Potent neuroprotective role of novel melatonin derivatives for management of central neuropathy induced by acrylamide in rats. Medicinal Chemistry45: 5452–5459.
2.
BullPJBrookeRKCockerJ, et al. (2005) An occupational hygiene investigation of exposure to acrylamide and the role for urinary S-carboxyethyl-cysteine (CEC) as a biological marker. Annals of Occupational Hygiene49: 683–690.
3.
CasabonaG (1997) Intracellular signal modulation: A pivotal role for protein kinase C. Progress in Neuro-Psychopharmacology and Biological Psychiatry21: 407–425.
4.
Chun-HongXRobertsEALu-ShiunH, et al. (2003) Abnormal neurofilament transport caused by targeted disruption of neuronal kinesin heavy chain KIF5A. Journal of Cell Biology161: 55–66.
5.
DoroudchiMMDurhamHD (2015) Activation of NMDA receptors and Ca2+/calmodulin-dependent protein kinase participate in phosphorylation of neurofilaments induced by protein kinase C. Journal of Neuroscience Research50: 514–521.
6.
DrummondENayakSPiresG, et al. (2018) Isolation of amyloid plaques and neurofibrillary tangles from archived Alzheimer’s disease tissue using laser-capture microdissection for downstream proteomics. Methods in Molecular Biology1723: 319–334.
7.
ElderGAFriedrichVLBoscoP, et al. (1998) Absence of the mid-sized neurofilament subunit decreases axonal calibers, levels of light neurofilament (NF-L), and neurofilament content. Journal of Cell Biology141: 727–739.
8.
ElderGAFriedrichVLMargitaA, et al. (1999) Age-related atrophy of motor axons in mice deficient in the mid-sized neurofilament subunit. Journal of Cell Biology146: 181–192.
9.
FrédéricDMarie-PauleMMyriam EscobarK, et al. (2005) Neurotoxic calcium transfer from endoplasmic reticulum to mitochondria is regulated by cyclin-dependent kinase 5-dependent phosphorylation of tau. Journal of Neuroscience25: 4159–4168.
10.
HahnKDebiasioRTaylorDL (1992) Patterns of elevated free calcium and calmodulin activation in living cells. Nature359: 736–738.
11.
HisanagaSMatsuokaYNishizawaK, et al. (1994) Phosphorylation of native and reassembled neurofilaments composed of NF-L, NF-M, and NF-H by the catalytic subunit of cAMP-dependent protein kinase. Molecular Biology of the Cell5: 161–172.
12.
HollanderBABennettGSShawG (2010) Localization of sites in the tail domain of the middle molecular mass neurofilament subunit phosphorylated by a neurofilament-associated kinase and by casein kinase I. Journal of Neurochemistry66: 412–420.
13.
KaurAGillKD (2010) Disruption of neuronal calcium homeostasis after chronic aluminium toxicity in rats. Basic & Clinical Pharmacology & Toxicology96: 118–122.
14.
KavitaSLahiriDK (2014) Cdk5 activity in the brain - multiple paths of regulation. Journal of Cell Science127: 2391–2400.
15.
LehningEJBalabanCDRossJF, et al. (2002) Acrylamide neuropathy. I. Spatiotemporal characteristics of nerve cell damage in rat cerebellum. Neurotoxicology23: 397–414.
16.
LlorensJ (2013) Toxic neurofilamentous axonopathies: Accumulation of neurofilaments and axonal degeneration. Journal of Internal Medicine273: 478–489.
17.
LopachinRM (2004) The changing view of acrylamide neurotoxicity. Neurotoxicology25: 617–630.
18.
LopesJPAgostinhoP (2011) CDK5: Multitasking between physiological and pathological conditions. Progress in Neurobiology94: 49–63.
19.
LopezJRAlvinLSalvatoreO, et al. (2010) Increased intraneuronal resting Ca2+ in adult Alzheimer’s disease mice. Journal of Neurochemistry105: 262–271.
20.
MachadoAKPanAYDaST, et al. (2016) Upstream pathways controlling mitochondrial function in major psychosis: A focus on bipolar disorder. Canadian Journal of Psychiatry Revue Canadienne De Psychiatrie61: 446–456.
21.
MclachlanDRWongLBergeronC, et al. (1987) Calmodulin and calbindin D28 K in Alzheimer disease. Alzheimer Disease & Associated Disorders1: 171–179.
22.
MehriSMeshkiMAHosseinzadehH (2015) Linalool as a neuroprotective agent against acrylamide-induced neurotoxicity in Wistar rats. Drug & Chemical Toxicology38: 162–166.
23.
O’DayDHEshakKMyreMA (2015) Calmodulin binding proteins and Alzheimer’s disease. Journal of Alzheimers Disease46: 553–569.
24.
ParkJKamendulisLMFriedmanMA, et al. (2002) Acrylamide-induced cellular transformation. Toxicological Sciences65: 177–183.
25.
PerrotREyerJ (2009) Neuronal intermediate filaments and neurodegenerative disorders. Brain Research Bulletin80: 282–295.
26.
Qing-ShanWLi-YanHCui-LiZ, et al. (2008) 2,5-hexanedione (HD) treatment alters calmodulin, Ca2+/calmodulin-dependent protein kinase II, and protein kinase C in rats’ nerve tissues. Toxicology and Applied Pharmacology232: 60–68.
27.
SharmaMSharmaPPantHC (2010) CDK-5-mediated neurofilament phosphorylation in SHSY5Y human neuroblastoma cells. Journal of Neurochemistry73: 79–86.
28.
SimpsonPBRussellJT (1998) Role of mitochondrial Ca2+ regulation in neuronal and glial cell signalling. Brain Research Reviews26: 72–81.
29.
SongFZhangQKouR, et al. (2012) 2,5-hexanedione altered the degradation of low-molecular-weight neurofilament in rat nerve tissues. Food & Chemical Toxicology50: 4277–4284.
30.
SufangYXiulanZTianliangZ, et al. (2005) Acrylamide-induced changes in the neurofilament protein of rat cerebrum fractions. Neurochemical Research30: 1079–1085.
31.
TaniiHHashimotoK (1985) Effect of acrylamide and related compounds on glycolytic enzymes of rat brain. Toxicology Letters26: 79–84.
32.
WeiHYGuoZQCuiSJ, et al.(2007) ApoCalmodulin and Ca2+-independent calmodulin-binding proteins. Progress in Biochemistry & Biophysics34: 124–131.
33.
WilkaniecACzapskiGAAdamczykA (2016) CDK5 at crossroads of protein oligomerization in neurodegenerative diseases: Facts and hypotheses. Journal of Neurochemistry136: 222–233.
34.
YanfeiH (2013) Toxicity of AlCl3 on osteoblast of rats cultured in vitro. Master Thesis, College of Veterinary Medicine Northeast Agricultural University, China.
35.
YasufumiSYoshitoKYoshiyukiM, et al. (2006) Involvement of calmodulin in neuronal cell death. Brain Research1083: 189–195.
36.
YuanARaoMVVeerannaCH. (2017) Neurofilaments and neurofilament proteins in health and disease. Cold Spring Harbor Perspectives in Biology9: a018309.
37.
YuequanSZhukovskayaNLQingG, et al. (2005) Calcium-independent calmodulin binding and two-metal-ion catalytic mechanism of anthrax edema factor. The Embo Journal24: 929–941.
38.
ZhangGYWangJHSharmaRK (1993) Purification and characterization of bovine brain calmodulin-dependent protein kinase II. The significance of autophosphorylation in the regulation of 63 kDa calmodulin-dependent cyclic nucleotide phosphodiesterase isozyme. Molecular & Cellular Biochemistry122: 159–169.
39.
ZhangQZhangPQiGJ, et al. (2018) Cdk5 suppression blocks SIRT1 degradation via the ubiquitin-proteasome pathway in Parkinson’s disease models. Biochimica et Biophysica Acta (BBA) - General Subjects1862: 1443–1451.
