Inositol hexakisphosphate kinase 2 promotes cell death of anterior horn cells in the spinal cord of patients with amyotrophic lateral ... View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2020-09-14

AUTHORS

Eiichiro Nagata, Natsuko Fujii, Saori Kohara, Chisa Okada, Tadayuki Satoh, Susumu Takekoshi, Masaki Takao, Ban Mihara, Shunya Takizawa

ABSTRACT

We have previously reported that inositol hexakisphosphate kinase (InsP6K)2 mediates cell death. InsP6K2 is abundantly expressed in anterior horn cells of the mammalian spinal cord. We investigated the role of InsP6K2 in spinal cords of patients with amyotrophic lateral sclerosis (ALS). Autopsy specimens of lumbar spinal cords from ten patients with sporadic ALS and five non-neurological disease patients (NNDPs) were obtained. We performed quantitative real-time PCR, immunostaining, and western blotting for InsP6K1, InsP6K2, InsP6K3, protein kinase B (Akt), casein kinase 2 (CK2), and 90-kDa heat-shock protein (HSP90). In contrast to InsP6K1 and InsP6K3 mRNA expression, InsP6K2 levels in anterior horn cells of the spinal cord were significantly increased in ALS patients compared to NNDPs. In ALS patients, InsP6K2 translocated from the nucleus to the cytoplasm. However, we observed a decrease in HSP90, CK2, and Akt activity in ALS patients compared to NNDPs. A previous study reported that InsP6K2 activity is suppressed after binding to HSP90 and subsequent phosphorylation and degradation by CK2, thus decreasing InsP6K2 activity. However, InsP7, which is generated by InsP6K2, can compete with Akt for PH domain binding. Consequently, InsP7 can inhibit Akt phosphorylation. Our results suggest that InsP6K2 is activated in the spinal cord of patients with ALS and may play an important role in ALS by inducing cell death mechanisms via Akt, CK2, and HSP90 pathways. More... »

PAGES

6479-6485

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s11033-020-05688-w

DOI

http://dx.doi.org/10.1007/s11033-020-05688-w

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1130839132

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/32929655


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37 schema:description We have previously reported that inositol hexakisphosphate kinase (InsP6K)2 mediates cell death. InsP6K2 is abundantly expressed in anterior horn cells of the mammalian spinal cord. We investigated the role of InsP6K2 in spinal cords of patients with amyotrophic lateral sclerosis (ALS). Autopsy specimens of lumbar spinal cords from ten patients with sporadic ALS and five non-neurological disease patients (NNDPs) were obtained. We performed quantitative real-time PCR, immunostaining, and western blotting for InsP6K1, InsP6K2, InsP6K3, protein kinase B (Akt), casein kinase 2 (CK2), and 90-kDa heat-shock protein (HSP90). In contrast to InsP6K1 and InsP6K3 mRNA expression, InsP6K2 levels in anterior horn cells of the spinal cord were significantly increased in ALS patients compared to NNDPs. In ALS patients, InsP6K2 translocated from the nucleus to the cytoplasm. However, we observed a decrease in HSP90, CK2, and Akt activity in ALS patients compared to NNDPs. A previous study reported that InsP6K2 activity is suppressed after binding to HSP90 and subsequent phosphorylation and degradation by CK2, thus decreasing InsP6K2 activity. However, InsP7, which is generated by InsP6K2, can compete with Akt for PH domain binding. Consequently, InsP7 can inhibit Akt phosphorylation. Our results suggest that InsP6K2 is activated in the spinal cord of patients with ALS and may play an important role in ALS by inducing cell death mechanisms via Akt, CK2, and HSP90 pathways.
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45 Akt
46 Akt activity
47 Akt phosphorylation
48 HSP90 pathway
49 Hsp90
50 InsP6K1
51 InsP6K2
52 InsP6K3
53 InsP6K3 mRNA expression
54 InsP7
55 NNDPs
56 PCR
57 PH domain
58 Western blotting
59 activity
60 amyotrophic lateral sclerosis
61 anterior horn cells
62 autopsy specimens
63 blotting
64 casein kinase 2
65 cell death
66 cell death mechanisms
67 cells
68 contrast
69 cord
70 cytoplasm
71 death
72 death mechanisms
73 decrease
74 degradation
75 disease patients
76 domain
77 expression
78 heat shock proteins
79 hexakisphosphate kinase
80 horn cells
81 important role
82 inositol
83 inositol hexakisphosphate kinases
84 kinase
85 kinase 2
86 kinase B
87 lateral sclerosis
88 levels
89 lumbar spinal cord
90 mRNA expression
91 mammalian spinal cord
92 mechanism
93 nucleus
94 pathway
95 patients
96 phosphorylation
97 previous studies
98 protein
99 protein kinase B
100 quantitative real-time PCR
101 real-time PCR
102 results
103 role
104 role of InsP6K2
105 sclerosis
106 specimens
107 spinal cord
108 sporadic amyotrophic lateral sclerosis
109 study
110 subsequent phosphorylation
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