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Binding of IDPN (β,β′‐iminodipropionitrile) to rat spinal cord: Possible implication in the mechanism of spheroid formation in amyotrophic lateral sclerosis
Author(s) -
Kato Takeo,
Suzuki Junichi,
Hayakawa Hiroyoshi,
Wada Manabu,
Kawanami Toru,
Kurita Keiji,
Ikezawa Yoshihiro,
Ishikawa Kiichi,
Sasaki Hideo
Publication year - 1997
Publication title -
neuropathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.701
H-Index - 61
eISSN - 1440-1789
pISSN - 0919-6544
DOI - 10.1111/j.1440-1789.1997.tb00017.x
Subject(s) - spinal cord , pons , medulla oblongata , amyotrophic lateral sclerosis , medicine , endocrinology , cerebellum , urea , anatomy , chemistry , central nervous system , biology , biochemistry , neuroscience , disease
β,β′‐iminodipropionitrile (IDPN) produces ‘spheroids’ similar to those in certain cases of amyotrophic lateral sclerosis (ALS). Therefore, the target molecule of IDPN could be important to the understanding of the molecular mechanism of spheroid formation in ALS. Wistar rats were injected ip with 14 C‐labeled IDPN ( 14 C‐IDPN) and killed at 0.5, 1, 3, 6, 12 and 24 h thereafter. The radioactivity in each organ increased rapidly and reached the maximum at 0.5–1 h after 14 C‐IDPN injection. Thereafter, a rapid decrease occurred until 6 h, followed by a gradual decline until 24 h. The radioactivity in the cerebral cortex, diencephalon and cerebellum was higher than in the pons, medulla oblongata and spinal cord. Although high in the visceral organs and skeletal muscles, no or little radioactivity was detected in fat tissue. Autoradiography also confirmed these results. In three rats, 14 C‐IDPN was injected to the lumbar enlargement of the spinal cord. Six hours after injection, the segment was removed and homogenized with physiological saline (PS). After centrifugation, the supernatant was obtained (PS fraction). The pellet was resuspended with 4 mol/L urea and the supernatant was obtained (urea fraction). Each fraction was analysed by gel filtration. A peak of radioactivity was observed at the elution fraction Nos 19 and 20 (consistent with free 14 C‐IDPN) when PS fraction was applied. On application of urea fraction, another peak was obtained at the elution fractions Nos 8 and 9 (MW 60∼80 kDa). The present study demonstrates that 14 C‐IDPN does not selectively accumulate to the spinal cord and suggests that an IDPN‐binding molecule with an MW of 60–80 kDa is present in the spinal cord. The molecule may be related to the pathological process of spheroid formation in ALS.