Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.22.36 (caspase-1)
 6,285 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chemical-induced oxidative stress to a cell can signal many cellular responses which include proliferation, differentiation, hemeostasis, apoptosis or necrosis. To better understand the underlying molecular mechanisms after exposure to chemicals, we investigated the signal transduction pathways, in particular the mitogen-activated protein kinase (MAPK) pathway and the ICE/Ced-3 protease (caspase) pathway, activated by different agents. Butylated hydroxyanisol (BHA) and its metabolite, t-butyl-hydroquinone (tBHQ), both are well known phenolic antioxidants used in food preservatives, strongly activated c-Jun N-terminal kinase 1 (JNK1) and/or extracellular signal-regulated protein kinase 2 (ERK2) in a dose- and time-dependent fashion. Pretreatment with free radical scavengers N-acetyl-L-cysteine (NAC), glutathione (GSH), or vitamin E, inhibited ERK2 activation and, to a much lesser extent, JNK 1 activation by BHA and tBHQ, implicating the role of oxidative stress. Under conditions where JNK1 and ERK2 were activated, BHA also activated transcription factors nuclear factor kappa B (NF-kappaB), activated-protein-1 (AP-1), and anti-oxidant response element (ARE), leading to induction of genes such as c-jun, and c-fos. At relatively high concentrations, BHA and tBHQ stimulated proteolytic activity of ICE/Ced3 cysteine proteases, and caused apoptosis, which was blocked by pretreatment with NAC. Further increase in concentrations lead to rapid cell death predominantly occurred via necrosis. Some naturally occurring phytochemicals, such as phenylethyl isothiocyanate (PEITC), green tea polyphenols (GTP), and sulfarophane, which have been shown to be potent inducers of Phase II enzymes, also differentially regulated the activities of JNK, ERK, or CPP-32, in a time- and dose-dependent manner. Our data, together with the work of others, enable us to propose a model in which low concentrations of these chemicals (e.g., BHA, PEITC) activate MAPKs leading to induction of gene expression (e.g., c-jun, c-fos, GSI) which may protect the cells against toxic insults and enhance cell survival. At relatively high concentrations, these agents activated both MAPKS, and the ICE/Ced-3 caspase pathway, leading to apoptosis. The exact mechanisms by which MAPK and caspases are activated by these agents are currently unknown, but may involve oxidative modification of glutathione (GSH) and/or protein thiols, and/or generation of secondary messengers, ceramide and calcium, which further activate downstream events. Taken together, our results suggest that chemicals including phenolic antioxidants activate MAPK pathways which may lead to the induction of genes producing protection and survival mechanisms, as well as the ICE/Ced-3 protease pathway, leading to apoptosis. The balancing amongst these pathways may dictate the fate of the cells upon exposure to chemicals.
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PMID:Differential activation of MAPK and ICE/Ced-3 protease in chemical-induced apoptosis. The role of oxidative stress in the regulation of mitogen-activated protein kinases (MAPKs) leading to gene expression and survival or activation of caspases leading to apoptosis. 1267 Dec 99

Neonicotinoids (NEOs), as the most widely used pesticides, pose a serious threat to water ecosystems, especially clothianidin (CLO). However, the degradation behavior of CLO, as a new type of persistent organic pollutant, is rarely studied in wastewater treatment. To bridge this gap, heterogeneous electro-Fenton system using three-dimension electrodes made of biochar-supported zero-valent iron nanoparticle hybrid material (NZVI-BC), abbreviated as 3D-ICE-EF system, is invented and initially applied in CLO wastewater degradation, without the addition of Fenton reagent. NZVI-BC in 3D-ICE-EF system can concentrate CLO on electrodes by excellent adsorption and effectively eliminate it to achieve self-cleaning effect. In addition, the deposition of iron mud (Fe(OH)3) and the circular utilization of Fe in Fenton system is effectively improved by the addition of hydroquinone (HQ) in 3D-ICE-EF system. The pH applicable scope of Fenton system is extended to alkaline condition by the applications of NZVI-BC electrodes. The increase in the acidity of electrolyte is considered the primary reason of the high degradation efficiency of CLO in 3D-ICE-EF system at an initial pH of 9.0. The degradation performance of 3D-ICE-EF system tends to be promoted by the increase of current intensity and air flow rate. Seven plausible mechanisms of CLO degradation were identified in 3D-ICE-EF system. The ecotoxicity evaluation of degradation products indicated that CLO degradation in 3D-ICE-EF system exhibits a remarkable tendency to reduce toxicity levels.
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PMID:Heterogeneous electro-Fenton using three-dimension NZVI-BC electrodes for degradation of neonicotinoid wastewater. 3262 28