The calcineurin antagonist RCAN1-4 is induced by exhaustive exercise in rat skeletal muscle.

The aim of this work was to study the regulation of the calcineurin antagonist regulator of calcineurin 1 (RCAN1) in rat skeletal muscles after exhaustive physical exercise, which is a physiological modulator of oxidative stress. Three skeletal muscles, namely extensor digitorum longus (EDL), gastrocnemius, and soleus, were investigated. Exhaustive exercise increased RCAN1-4 protein levels in EDL and gastrocnemius, but not in soleus. Protein oxidation as an index of oxidative stress was increased in EDL and gastrocnemius, but remained unchanged in soleus. However, lipid peroxidation was increased in all three muscles. CuZnSOD and catalase protein levels were increased at 3 h postexercise in soleus, whereas they remained unchanged in EDL and gastrocnemius. Calcineurin enzymatic activity declined in EDL and gastrocnemius but not in soleus, and its protein expression was decreased in all three muscles. The level of PGC1-α protein remained unchanged, whereas the protein expression of the transcription factor NFATc4 was decreased in all three muscles. Adiponectin expression was increased in all three muscles. RCAN1-4 expression in EDL and gastrocnemius muscles was augmented by the oxidative stress generated from exhaustive exercise. We propose that increased RCAN1-4 expression and the signal transduction pathways it regulates represent important components of the physiological adaptation to exercise-induced oxidative stress.

Dietary α-lactalbumin supplementation alleviates normocaloric western diet-induced glucose intolerance in Göttingen minipigs.

OBJECTIVE: The pandemic of obesity in Western countries is mainly due to the high-fat, high-energy diet prevailing there. Obesity-associated metabolic disorders are the consequence of fat mass increase leading to altered adipokine secretion, hyperlipemia, oxidant stress, low-grade inflammation, and eventually glucose intolerance. Yet not all people consuming a Western diet become obese, and the question is raised whether these people are also at risk of developing metabolic disorders. METHODS: Glucose tolerance, lipid profile, and oxidant and inflammation status were investigated longitudinally in lean Göttingen minipigs receiving for 16 weeks either a normal diet (ND), a Western diet (WD), or a Western diet supplemented with a whey protein isolate (WPI) rich in α-lactalbumin known to improve glucose tolerance. ND and WD were supplied isoenergetically. RESULTS: Lean minipigs fed WD displayed glucose intolerance and altered lipid profile after 6 weeks of diet but no inflammation or oxidative stress. Supplementation with WPI alleviated glucose intolerance by improving insulin secretion, but not lipid profile. CONCLUSIONS: Western diet consumption is deleterious for glucose tolerance even in the absence of fat mass accretion, and dyslipemia is a major determinant for this metabolic dysfunction. Stimulating insulin secretion with a WPI is an effective strategy to improve glucose tolerance.

Ecotoxicological effects of diuron and chlorotoluron nitrate-induced photodegradation products: monospecific and aquatic mesocosm-integrated studies.

The ecotoxicological impact of nitrate-induced photodegradation products of diuron and chlorotoluron was studied through monospecific biotests conducted in conjunction with experiments in outdoor aquatic mesocosms. Organisms representing three trophic levels were used: two heterotrophic microorganisms, the luminescent bacterium Vibrio fischeri and the ciliated protozoa Tetrahymena pyriformis, and one metazoa, the gastropod Lymnaea stagnalis. Among the variety of the phenylurea photoproducts, the N-formylated ones appeared clearly more toxic than the parent compounds towards the microorganisms, whereas the nitroderivatives showed a similar toxicity. Using photodegraded solutions of diuron, toxicity was maintained or even increased during disappearance of the initial herbicide, demonstrating that some of the photoproducts may have an impact additively or in synergy. Enzymatic biomarker assays performed on Lymnaea stagnalis exposed under monospecific conditions showed significant effects, due to the combination of nitrate with the pesticide and its photoproducts. A positive impact on snail fecundity was observed with chlorotoluron both under monospecific laboratory and integrated mesocosm conditions. Oviposition stimulation took place when first- and second-generation photoproducts were predominant.

Role for mitogen-activated protein kinases in phenobarbital-induced expression of cytochrome P450 2B in primary cultures of rat hepatocytes.

Phenobarbital (PB) alters expression of numerous hepatic genes, including genes of cytochrome P450 2B1 and 2B2 (CYP2B). However, the intracellular mechanisms remain to be fully elucidated. The present study investigated the involvement of mitogen-activated protein kinases (MAPKs) in rat hepatocytes in primary culture. We showed that PB induced an early, dose-dependent activation of ERK (extracellular signal-regulated kinase), JNK (c-Jun N-terminal kinase) and p38 MAPKs. Regarding the PB (1mM) induction of CYP2B mRNA expression, while chemically inhibiting JNK had no effect, specific inhibitors of the ERK (U0-126) and p38 (SB-203580) pathways up- and down-regulated this expression, respectively. However, although such a regulation was confirmed when testing the effect of a dominant negative mutant of the ERK pathway on the CYP2B2 enhancer-promoter activity, no such transcriptional role was found with the p38 pathway. Moreover, upon arrest of transcription, the stability of CYP2B mRNA remained unaffected by SB-203580. In conclusion, we show that the ERK pathway negatively regulates CYP2B2 enhancer-promoter activity and that, despite p38 activation upon PB exposure, the sensitivity of CYP2B mRNA expression to SB-203580 appears to be unrelated to this kinase.