Crotonaldehyde accumulates in glial cells of Alzheimer’s disease brain

Abstract

Several studies have documented the involvement of oxidative stress represented by lipid peroxidation in the pathogenesis of Alzheimer's disease (AD). To test whether the highly reactive carbonyl crotonaldehyde (CRA), generated during lipid peroxidation, is involved in AD, we performed an immunohistochemical analysis in AD and age-matched control hippocampi using a specific antibody against protein-bound CRA (P-CRA). In the AD cases, P-CRA immunoreactivity was preferentially localized in reactive astrocytes and microglia around senile plaques (SPs) and those present in the neuropil, while it was weakly detectable in neurons and neurofibrillary tangles. P-CRA immunoreactivity was also localized in all portions of diffuse SPs and the dystrophic neurites of neuritic and classical SPs, but was undetectable in amyloid cores. Age-matched controls showed P-CRA immunoreactivity only very weakly in neurons. In contrast to P-CRA, immunoreactivities for protein-bound acrolein and 4-hydroxy-2-nonenal were mainly localized to neurons and rarely seen in glial cells. Our results suggest that increased oxidative stress and CRA formation in glial cells is implicated in the disease processes of AD.

Immunohistochemical Detection of Polyunsaturated Fatty Acid Oxidation Markers in Acetaminophen-Induced Liver Injury in Rats

“…These timecourse changes of areas positively immunostained for Bax and these oxidation markers are dependent on the development of necrosis in APAP-induced liver injury. DISCUSSION PRL, HEL, 4-HHE-modified protein and CRA-lysine has been immunohistochemically detected in diverse pathological situations in humans [19,21,23,38,39,44] and experimenta l anima ls [9,15,33,40]. PRL has been immunohistochemically detected in atherosclerotic lesions of hypercholesterolemic rabbits [15].…”

“…4-HHE-modified protein immunoreactivity was localized in liver of patients with chronic hepatitis C [23], spinal cords from patients with amyotrophic lateral sclerosis [39], in human atherosclerotic aorta [34] and intense light-exposed rat retina [40]. CRA-lysine has been immunohistochemically detected in spinal cord of ALS patients [38] and Alzheimer's disease brain [21]. To our knowledge, this is the first report about expression of PRL, HEL, 4-HHE-histidine and CRA-lysine in APAP-induced liver injury.…”

“…Recently, polyunsaturated fatty acid (PUFA) oxidation markers, such as N ε -propanoyl-modified lysine (PRL), N ε -hexanoyl-modified lysine (HEL) 4-hydroxyhexenal-modified histidine (4-HHE-histidine) and crotonaldehyde-modified lysine (CRA-lysine), have been given more attention as factors related to the processes of diverse pathological situations [9,15,19,21,23,33,[38][39][40]44]. PUFA is easily peroxidized by free radicals and enzymes, and peroxidation of PUFA results in compromised integrity of cellular membranes and leads to lipid hydroperoxide as a major reaction product, and lipid hydroperoxide is decomposed into aldehyde [20].…”

Acute exposure to crotonaldehyde induces dysfunction of immune system in male Wistar rats

“…Crotonaldehyde can also be formed endogenously from lipid metabolism. It works as an initiator or end product of lipid peroxidation (Kawaguchi-Niida et al, 2006;Pan and Chung, 2002;Esterbauer et al, 1991;Chung et al, 1999Chung et al, , 1996. Furthermore, it can be produced during metabolism of the carcinogens N-nitrosopyrrolidine and 1, 3-butadiene (Sharer et al, 1992;Filser et al, 2001;Elfarra et al, 1991;Elfarra, 1992, 1993;Cheng and Ruth, 1993).…”

Transcript profiling analysis of <i>in vitro</i> cultured THP-1 cells after exposure to crotonaldehyde

“…Crotonaldehyde is released into the atmosphere from the combustion of wood, tobacco and engine exhausts (Lipari et al, 1984;Jha et al, 2007). It occurs naturally in food and is endogenously generated by lipid peroxidation (Chung et al, 1996;Kawaguchi-Niida et al, 2006). Humans are exposed to crotonaldehyde in work places, and from tobacco smoke, environmental pollution, food, and beverages.…”