TY - JOUR
T1 - Cobalt induces neurodegenerative damages through Pin1 inactivation in mice and human neuroglioma cells
AU - Zheng, Fuli
AU - Li, Yuqing
AU - Zhang, Fengshun
AU - Sun, Yi
AU - Zheng, Chunyan
AU - Luo, Zhousong
AU - Wang, Yuan Liang
AU - Aschner, Michael
AU - Zheng, Hong
AU - Lin, Liqiong
AU - Cai, Ping
AU - Shao, Wenya
AU - Guo, Zhenkun
AU - Zheng, Min
AU - Zhou, Xiao Zhen
AU - Lu, Kun Ping
AU - Wu, Siying
AU - Li, Huangyuan
N1 - Publisher Copyright:
© 2021 Elsevier B.V.
PY - 2021/10/5
Y1 - 2021/10/5
N2 - Cobalt is a hazardous material that has harmful effects on neurotoxicity. Excessive exposure to cobalt or inactivation of the unique proline isomerase Pin1 contributes to age-dependent neurodegeneration. However, nothing is known about the role of Pin1 in cobalt-induced neurodegeneration. Here we find that out of several hazardous materials, only cobalt dose-dependently decreased Pin1 expression and alterations in its substrates, including cis and trans phosphorylated Tau in human neuronal cells, concomitant with neurotoxicity. Cobalt-induced neurotoxicity was aggravated by Pin1 genetic or chemical inhibition, but rescued by Pin1 upregulation. Furthermore, less than 4 μg/l of blood cobalt induced dose- and age-dependent Pin1 downregulation in murine brains, ensuing neurodegenerative changes. These defects were corroborated by changes in Pin1 substrates, including cis and trans phosphorylated Tau, amyloid precursor protein, β amyloid and GSK3β. Moreover, blood Pin1 was downregulated in human hip replacement patients with median blood cobalt level of 2.514 μg/l, which is significantly less than the safety threshold of 10 μg/l, suggesting an early role Pin1 played in neurodegenerative damages. Thus, Pin1 inactivation by cobalt contributes to age-dependent neurodegeneration, revealing that cobalt is a hazardous material triggering AD-like neurodegenerative damages.
AB - Cobalt is a hazardous material that has harmful effects on neurotoxicity. Excessive exposure to cobalt or inactivation of the unique proline isomerase Pin1 contributes to age-dependent neurodegeneration. However, nothing is known about the role of Pin1 in cobalt-induced neurodegeneration. Here we find that out of several hazardous materials, only cobalt dose-dependently decreased Pin1 expression and alterations in its substrates, including cis and trans phosphorylated Tau in human neuronal cells, concomitant with neurotoxicity. Cobalt-induced neurotoxicity was aggravated by Pin1 genetic or chemical inhibition, but rescued by Pin1 upregulation. Furthermore, less than 4 μg/l of blood cobalt induced dose- and age-dependent Pin1 downregulation in murine brains, ensuing neurodegenerative changes. These defects were corroborated by changes in Pin1 substrates, including cis and trans phosphorylated Tau, amyloid precursor protein, β amyloid and GSK3β. Moreover, blood Pin1 was downregulated in human hip replacement patients with median blood cobalt level of 2.514 μg/l, which is significantly less than the safety threshold of 10 μg/l, suggesting an early role Pin1 played in neurodegenerative damages. Thus, Pin1 inactivation by cobalt contributes to age-dependent neurodegeneration, revealing that cobalt is a hazardous material triggering AD-like neurodegenerative damages.
KW - Cobalt
KW - Neurodegeneration
KW - Phosphorylated Tau (P-Tau)
KW - Pin1
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U2 - 10.1016/j.jhazmat.2021.126378
DO - 10.1016/j.jhazmat.2021.126378
M3 - Article
C2 - 34175703
AN - SCOPUS:85109536802
SN - 0304-3894
VL - 419
JO - Journal of Hazardous Materials
JF - Journal of Hazardous Materials
M1 - 126378
ER -