25 research outputs found
Radiation makes cells select the form of death dependent on external or internal exposure: apoptosis or pyroptosis
Abstract Internal radiation exposure from neutron-induced radioisotopes environmentally activated following atomic bombing or nuclear accidents should be considered for a complete picture of pathologic effects on survivors. Acute and localized high dose radiation exposure from hot particles taken into the body must induce cell death and severe damage to tissues, whether they are proliferating or not. However, very little the cellular and molecular mechanisms underlying this internal radiation pathology has been investigated. Male Wistar rats were internally exposed to 56MnO2 powder by inhalation. Small intestine samples were investigated by histological staining at acute phase (6 h, 3 days and 14 days) and late phase (2, 6 and 8 months) after the exposure. Histological location and chemical properties of the hot particles embedded in small intestinal tissues were analyzed by synchrotron radiation—X-ray fluorescence—X-ray absorption near-edge structure (SR–XRF–XANES). Hot particles located in the intestinal cavity were identified as accumulations of Mn and iron. Pathological changes showed evidence of crypt shortening, massive cell death at the position of stem cell zone, including apoptosis and pyroptosis from 6 h through 8 months in the internal exposed rats
Structural Insight into an Alzheimer’s Brain-Derived Spherical Assembly of Amyloid β by Solid-State NMR
Accumulating
evidence suggests that various neuroÂdegenerative
diseases, including Alzheimer’s disease (AD), are linked to
cytotoxic diffusible aggregates of amyloid proteins, which are metastable
intermediate species in protein misfolding. This study presents the
first site-specific structural study on an intermediate called amyloÂspheroid
(ASPD), an AD-derived neurotoxin composed of oligomeric amyloid-β
(Aβ). Electron microscopy and immunological analyses using ASPD-specific
“conformational” antibodies established synthetic ASPD
for the 42-residue Aβ(1–42) as an excellent structural/morphological
analogue of native ASPD extracted from AD patients, the level of which
correlates with the severity of AD. <sup>13</sup>C solid-state NMR
analyses of approximately 20 residues and interstrand distances demonstrated
that the synthetic ASPD is made of a homogeneous single conformer
containing parallel β-sheets. These results provide profound
insight into the native ASPD, indicating that Aβ is likely to
self-assemble into the toxic intermediate with β-sheet structures
in AD brains. This approach can be applied to various intermediates
relevant to amyloid diseases
Impact of Local High Doses of Radiation by Neutron Activated Mn Dioxide Powder in Rat Lungs: Protracted Pathologic Damage Initiated by Internal Exposure
Internal radiation exposure from neutron-induced radioisotopes environmentally activated following atomic bombing or nuclear accidents should be considered for a complete picture of pathologic effects on survivors. Inhaled hot particles expose neighboring tissues to locally ultra-high doses of β-rays and can cause pathologic damage. 55MnO2 powder was activated by a nuclear reactor to make 56MnO2 which emits β-rays. Internal exposures were compared with external-rays. Male Wistar rats were administered activated powder by inhalation. Lung samples were observed by histological staining at six hours, three days, 14 days, two months, six months and eight months after the exposure. Synchrotron radiation-X-ray fluorescence-X-ray absorption near-edge structure (SR-XRF-XANES) was utilized for the chemical analysis of the activated 56Mn embedded in lung tissues. 56Mn beta energy spectrum around the particles was calculated to assess the local dose rate and accumulated dose. Hot particles located in the bronchiole and in damaged alveolar tissue were identified as accumulations of Mn and iron. Histological changes showed evidence of emphysema, hemorrhage and severe inflammation from six hours through eight months. Apoptosis was observed in the bronchiole epithelium. Our study shows early event damage from the locally ultra-high internal dose leads to pathogenesis. The trigger of emphysema and hemorrhage was likely early event damage to blood vessels integral to alveolar walls