Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.22.61 (caspase-8)
 6,833 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Acrolein, a highly reactive alpha,beta-unsaturated aldehyde, is an omnipresent environmental pollutant. Chronic and acute human exposures occur through exogenous and endogenous sources, including food, vapors of overheated cooking oil, house and forest fires, cigarette smoke, and automobile exhaust. Acrolein is a toxic byproduct of lipid peroxidation, which has been implicated in pulmonary, cardiac, and neurodegenerative diseases. This study shows that p53 is an initiating factor in acrolein-induced death receptor activation during apoptosis in A549 human lung cells. Exposure of cells to acrolein (0-50 micromol/L) mainly caused apoptosis, which was manifested by execution phase events such as condensation of nuclear chromatin, phosphatidylserine externalization, and poly(ADP-ribose) polymerase (PARP) cleavage. Levels of necrosis (approximately 5%) were low. Acrolein triggered the death receptor pathway of apoptosis, causing elevation of Fas ligand (FasL) and translocation of adaptor protein Fas-associated death domain to the plasma membrane. Acrolein caused activation of caspase-8, caspase-2, caspase-7, and the cross-talk pathway mediated by Bid cleavage. Activation of p53 and increased expression of p53-upregulated modulator of apoptosis (PUMA) occurred in response to acrolein. FasL upregulation and caspase-8 activation were decreased by p53 inhibitor pifithrin-alpha and antioxidant polyethylene glycol catalase. These findings increase our knowledge about the induction of cell death pathways by acrolein, which has important implications for human health.
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PMID:Acrolein induces apoptosis through the death receptor pathway in A549 lung cells: role of p53. 2039

High molecular weight hyperbranched polyglycerol (HPG) was selected for development as a soluble polymer support for the targeted selection and release of primary-amine containing peptides from a complex mixture. HPG has been functionalized with ester-linked aldehyde groups that can bind primary-amine containing peptides via a reductive alkylation reaction. Once bound, the high molecular weight of the polymer facilitates separation from a complex peptide mixture by employing either a 30 kDa molecular weight cutoff membrane or precipitation in acetonitrile. Following the removal of unbound peptides and reagents, subsequent hydrolysis of the ester linker releases the bound peptide into solution for analysis by mass spectrometry. Released peptides retain the linker moiety and are therefore characteristically mass-shifted. Four water-soluble cleavable aldehyde polymers (CAP1, CAP2, CAP3, and CAP4) ranging in types of linker groups, length of the linker groups, have been prepared and characterized, each demonstrating the ability to selectively enrich and sequence primary-amine peptides from a complex human proteome containing blocked (dimethylated amine) and unblocked (primary amine) peptides. The polymers have very low nonspecific peptide-binding properties while possessing significantly more reactive groups per milligram of the support than commercially available resins. The polymers exhibit a range of reactivities and binding capacities that depend on the type of linker group between the aldehyde group and the polymer. Using various linker structures, we also probed the mechanism of the observed dehydration of hydrolyzed peptides during matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) analysis.
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PMID:Development of soluble ester-linked aldehyde polymers for proteomics. 2177 40

Diatoms are ubiquitous and abundant primary producers that have been traditionally considered as a beneficial food source for grazers and for the transfer of carbon through marine food webs. However, many diatom species produce polyunsaturated aldehydes that disrupt development in the offspring of grazers that feed on these unicellular algae. Here we provide evidence that production of the physiological messenger nitric oxide increases after treatment with the polyunsaturated aldehyde decadienal in embryos of the sea urchin Paracentrotus lividus. At high decadienal concentrations, nitric oxide mediates initial apoptotic events leading to loss of mitochondrial functionality through the generation of peroxynitrite. At low decadienal concentrations, nitric oxide contributes to the activation of hsp70 gene expression thereby protecting embryos against the toxic effects of this aldehyde. When nitric oxide levels were lowered by inhibiting nitric oxide synthase activity, the expression of hsp70 in swimming blastula decreased and the proportion of abnormal plutei increased. However, in later pluteus stages nitric oxide was no longer able to exert this protective function: hsp70 and nitric oxide synthase expression decreased with a consequent increase in the expression of caspase-8. Our findings that nitric oxide production increases rapidly in response to a toxic exogenous stimulus opens new perspectives on the possible role of this gas as an important messenger to environmental stress in sea urchins and for understanding the cellular mechanisms underlying toxicity during diatom blooms.
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PMID:Nitric oxide mediates the stress response induced by diatom aldehydes in the sea urchin Paracentrotus lividus. 2202 85

Alcohol consumption affects gastric mucosa by multiple and complex mechanisms depending either by direct contact of ethanol or by indirect biological damage induced by its metabolite acetaldehyde. The present study aims at further investigating the mechanism of ethanol-induced gastric mucosa injury and the protective effect of astragaloside IV (AS-IV) in an aspect of mitochondrial oxidative stress and mitochondrial pathway of apoptosis. Using an array of experimental approaches, we have shown that the development of mitochondrial oxidative stress and associated apoptosis play crucial roles in the pathogenesis of gastric injury induced by ethanol. AS-IV inhibits mitochondrial oxidative stress by scavenging accumulation of malondialdehyde and decreasing the consumption of glutathione. AS-IV also prevents ethanol-induced apoptosis by modulating the activity of caspase-3 and caspase-9, the expression of Bax/Bcl-2, and the release of cytochrome C and apoptosis inducing factor. Moreover, AS-IV reduces ethanol-mediated activation of caspase-8 and breakage of Bid. This study thus indicates that AS-IV prevented ethanol-induced gastric damage by blocking activation of mitochondrial oxidative stress and mitochondrial pathway of apoptosis induced by ethanol in the gastric mucosa.
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PMID:Astragaloside IV Protects Ethanol-Induced Gastric Mucosal Injury by Preventing Mitochondrial Oxidative Stress and the Activation of Mitochondrial Pathway Apoptosis in Rats. 3147 58


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