Regulation of the unfolded protein response during dehydration stress in African clawed frogs, Xenopus laevis.

The unfolded protein response (UPR) is a wide-ranging cellular response to accumulation of malfolded proteins in the endoplasmic reticulum (ER) and acts as a quality control mechanism to halt protein processing and repair/destroy malfolded proteins under stress conditions of many kinds. Among vertebrate species, amphibians experience the greatest challenges in maintaining water and osmotic balance, the high permeability of their skin making them very susceptible to dehydration and challenging their ability to maintain cellular homeostasis. The present study evaluates the involvement of the UPR in dealing with dehydration-mediated disruption of protein processing in the tissues of African clawed frogs, Xenopus laevis.

Increased transcript levels and kinetic function of pyruvate kinase during severe dehydration in aestivating African clawed frogs, Xenopus laevis.

The African clawed frog, Xenopus laevis, can withstand extremely arid conditions through aestivation, resulting in dehydration and urea accumulation. Aestivating X. laevis reduce their metabolic rate, and rely on anaerobic glycolysis to meet reduced ATP demands.

The regulation of heat shock proteins in response to dehydration in Xenopus laevis.

African clawed frogs (Xenopus laevis) endure bouts of severe drought in their natural habitats and survive the loss of approximately 30% of total body water due to dehydration. To investigate molecular mechanisms employed by X. laevis during periods of dehydration, the heat shock protein response, a vital component of the cytoprotective stress response, was characterized.

Integrating toxicogenomics into human health risk assessment: lessons learned from the benzo[a]pyrene case study.

The use of short-term toxicogenomic tests to predict cancer (or other health effects) offers considerable advantages relative to traditional toxicity testing methods. The advantages include increased throughput, increased mechanistic data, and significantly reduced costs. However, precisely how toxicogenomics data can be used to support human health risk assessment (RA) is unclear.

Hepatic genotoxicity and toxicogenomic responses in Muta™Mouse males treated with dibenz[a,h]anthracene.

Dibenz[a,h]anthracene (DB[a,h]A) is a polycyclic aromatic hydrocarbon that is a by-product of combustion and a potent carcinogen. Few studies have investigated the effects of DB[a,h]A on mRNA and microRNA expression to dissect the mechanisms involved in carcinogenesis. In this study, mature male mice (Muta(™)Mouse) were exposed to 6.

Hepatic mRNA, microRNA, and miR-34a-target responses in mice after 28 days exposure to doses of benzo(a)pyrene that elicit DNA damage and mutation.

Benzo(a)pyrene (BaP) is a mutagenic carcinogen that is ubiquitous in our environment. To better understand the toxic effects of BaP and to explore the relationship between toxicity and toxicogenomics profiles, we assessed global mRNA and microRNA (miRNA) expression in Muta™Mouse. Adult male mice were exposed by oral gavage to 25, 50, and 75 mg/kg/day BaP for 28 days.

Transcriptional regulation of antioxidant enzymes by FoxO1 under dehydration stress.

Antioxidant defenses are an important part of adaptation to environmental stress for many organisms. This study analyzed responses to dehydration stress by manganese-dependent superoxide dismutase (MnSOD) and catalase, and the role of forkhead box class O type 1 (FoxO1) transcription factor in regulating their up-regulation, in selected tissues of the African clawed frogs, Xenopus laevis. Protein and mRNA levels of MnSOD and catalase were analyzed by immunoblotting and PCR.

Activation of extracellular signal-regulated kinases during dehydration in the African clawed frog, Xenopus laevis.

In its native environment the African clawed frog, Xenopus laevis, can experience seasonally arid conditions that impose dehydration stress. Activation of intracellular signal transduction cascades can mediate and coordinate biochemical responses to ameliorate dehydration stress. This study examines the extracellular signal-regulated kinase (ERK) signaling cascade, analyzing responses of both upstream and downstream components in six tissues of X.

Activation of antioxidant defense during dehydration stress in the African clawed frog.

The glutathione S-transferase (GST) and aldo-keto reductase (AKR) families of proteins are major groups of detoxifying enzymes that are known to be regulated by the NF-E2 related factor 2 (Nrf2) transcription factor via the antioxidant response element that is present in the promoter regions of GST and AKR genes. Expression of Nrf2, GST and AKR proteins was analyzed in the African clawed frog, Xenopus laevis, focusing on their responses to dehydration stress. Dehydration/rehydration cycles can generate oxidative stress and this could be ameliorated by enhancing antioxidant defenses.