Search

Humans are ubiquitously exposed to crotonaldehyde (CRA) endogenously and exogenously. Deeper knowledge of the pharmacological and toxicological characteristics and the mechanisms of CRA on vasculature is urgently needed for prevention of its harmfulness. The effects of acute and prolonged exposure to CRA were studied in rat isolated arteries and arterial smooth muscle cells (ASMCs). Instant exposure to CRA (1–300 μM) concentration-dependently declined the tension of pre-constricted arteries with an irreversible depression on the contractility. Prolonged exposure of rat coronary arteries (RCAs) to CRA concentration- and time-dependently depressed the arterial contractile responsiveness to various vasoconstrictors including depolarization, U46619, serotonin and Bay K8644 (an agonist of voltage-gated Ca2+ channels (VGCCs)). In fresh RCA ASMCs, CRA abated depolarization-induced elevation of intracellular Ca2+ ([Ca2+] i). Electrophysiological study revealed that acute exposure to CRA depressed the functions of Ca2+-activated Cl- channels (CaCCs), voltage-gated K+ (Kv) channels and inward rectifier K+ (Kir) channels in RCA ASMCs. Prolonged exposure of RCAs to CRA reduced the expressions of these ion channels in RCA ASMCs, disordered tissue frames, injured arterial cells, and increased autophagosomes in both ASMCs and endothelial cells. In rat aortic smooth muscle cells (A7r5), CRA exposure decreased the cell viability, elevated the intracellular levels of reactive oxygen species, reduced the mitochondrial membrane potential, and enhanced autophagy. Taken together, the present study for the first time portrays a clearer panoramic outline of the vascular effects and the mechanisms of CRA on arteries, demonstrates that CRA impairs arterial contractility, depresses VGCCs, CaCCs, Kv channels and Kir channels, reduces cell viability, and destroys the arterial histiocytes, and suggests that excessive oxidative stress, mitochondrial dysfunction and autophagy underlie these vascular damages. These findings are significant for the comprehensive evaluation of the vicious effects of CRA on arteries and suggest potential preventive strategies. [Display omitted] • Crotonaldehyde collapses the arterial contractile responsiveness to various agonists. • Crotonaldehyde impaires Ca2+, Cl- and K+ channels in the arterial smooth muscles. • Crotonaldehyde induces extensive histocytological injuries in rat coronary arteries. • Overoxidation, mitochondrial damage and autophagy underlie the arterial paralysis. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Crotonaldehyde in 1,3(n ,π*) states have been shown to possess a symmetry plane. • Crotonaldehyde in 1,3(n ,π*) states are significantly non-planar. • Couplings of internal rotations with others large amplitude motions can be important in dynamics. Abstract For trans- and cis -crotonaldehydes CH 3 CH CH CHO in the triplet and singlet lowest excited electronic states of n ,π* and π,π* types, the geometries of conformers, conformer energy differences, and conformational dynamics have been addressed using ab initio multi-reference techniques (CASSCF and CASPT2). The conformers of investigated molecules under study have been shown to possess a symmetry plane in 1,3(n ,π*) states and to be significantly non-planar in 1,3(π,π*) states. Couplings of asymmetric internal rotations around C C and C C bonds with others large amplitude molecular motions such as methyl torsion, non-planar distortions of CCHO, C CH C, and C CH(CH 3) fragments are discussed. The type of coupling between large-amplitude motions has been shown to be connected with the localization of electronic excitation. [ABSTRACT FROM AUTHOR]

Abstract Crotonaldehyde is a common environmental contaminant. Autophagy, apoptosis, and necrosis, were all respectively reported to be induced by crotonaldehyde. However, the relationships between programmed cell deaths, especially between autophagy and apoptosis, have not been elucidated. In the present study, alterations of autophagy, apoptosis and necrosis were investigated in human bronchial epithelial cells (BEAS-2B) exposed to crotonaldehyde, and effects of autophagy on apoptosis and necrosis were detected. We found that a high concentration (160 μmol/L, μM) of crotonaldehyde did not induce apoptosis, while a low concentration (80 μM) of crotonaldehyde induced autophagy, apoptosis and necrosis. In 80 μM crotonaldehyde-exposed BEAS-2B cells, autophagy and apoptosis exhibited a trend of increasing prior to decreasing with the increase of time, while the time point inducing the highest level of autophagy was 2 h, and that of apoptosis was 4 h. With the pretreatment of bafilomycin A 1 , the apoptosis was inhibited and the necrosis was enhanced significantly in cells exposed to 80 μM crotonaldehyde. Autophagy mediated the induction of apoptosis via the intrinsic apoptotic pathway. The results indicate that autophagy mediates the initiation of apoptosis and plays a role in protecting from necrosis in low concentrations of crotonaldehyde-exposed BEAS-2B cells. Graphical abstract fx1 Highlights • High concentration (160 μM) of crotonaldehyde does not induce apoptosis in BEAS-2B. • Low concentration (80 μM) of crotonaldehyde induces apoptosis in BEAS-2B. • Crotonaldehyde (80 μM)-induced autophagy promotes apoptosis and inhibits necrosis. • Autophagy induces apoptosis via the intrinsic apoptotic pathway. [ABSTRACT FROM AUTHOR]

Abstract: The critical node (CN) is an important stage during seed aging, which is related to effective genebank conservation. Previous studies have demonstrated that proteins undergo carbonylated modification at the CN in rice, indicating oxidative damage. However, the levels of reactive carbonyl species (RCS) and the associated scavenging system at the CN are largely unknown. In this study, we optimized methods for the extraction and analysis of RCS from dry rice embryos. In order to acquire seeds at the CN, rice seeds were subjected to natural conditions for 7, 9, 11 and 13 months, and the seed germination rates were reduced to 90%, 82%, 71% and 57%, respectively. We chose the stage with seed germination rate of 82% as the CN according to the rice seed vigor loss curve. The levels of crotonaldehyde and 4-hydroxy-(E)-2-nonenal (HNE) were significantly increased at the CN. In addition, genes encoding carbonyl-scavenging enzyme, including OsALDHs and OsAKRs , were significantly down-regulated at the CN, and reductions in the expression of OsALDH2-2 , OsALDH2-5 , OsALDH3-4 , OsALDH7 , OsAKR1 and OsAKR2 in particular could be responsible for RCS accumulation. Thus, the accumulations of crotonaldehyde and HNE and down-regulation of genes encoding carbonyl-scavenging enzyme might be related to an accelerating loss of seed viability at the CN. [ABSTRACT FROM AUTHOR]

Crotonaldehyde is an ubiquitous hazardous pollutant in the environment which can be produced naturally, artificially and endogenously. Acute exposure of crotonaldehyde was reported to induce severe lung injury in humans and experimental animals. However, the exact toxicity mechanisms of crotonaldehyde in organisms have not been fully explored. In the present study, we explored the role autophagy played in the cytotoxicity induced by crotonaldehyde in human bronchial epithelial cells (BEAS-2B), and the pathways that mediated autophagy, including the phosphatidylinositol 3-kinase (PI3K) pathway, the AMP-activated protein kinase (AMPK) pathway and the mitogen-activated protein kinase (MAPK) pathways, were examined and validated. We found that crotonaldehyde induced cytotoxicity and autophagy simultaneously in BEAS-2B cells, and blockage of autophagic flux significantly elevated the viability of BEAS-2B exposed to high concentrations of crotonaldehyde. Crotonaldehyde down-regulated the activity of PI3K pathway, and elevated the activities of AMPK and MAPK pathways. Pretreatment of specific agonist or antagonist of these pathways could inhibit autophagy and partly improve the viability. These results suggested that acute exposure of crotonaldehyde induced cell death mediated by autophagy, which might be helpful to elucidate the toxicity mechanisms of crotonaldehyde and contribute to environmental and human health risk assessment. [ABSTRACT FROM AUTHOR]