Overload Induced Heat Shock Proteins (HSPs), MAPK and miRNA (miR-1 and miR133a) Response in Insulin-Resistant Skeletal Muscle

Background: Insulin resistance (IR) may decrease muscle adaptability. Heat shock proteins (HSPs), mitogen-activated protein kinases (MAPKs), and miRNA are thought to play a role in muscle hypertrophy but it is unclear if IR may affect their regulation. Methods: Soleus muscles of lean Zucker (LZ) and insulin resistant obese Zucker (OZ) rats were overloaded for 7 or 21 days and subjected to immunoblotting and RT-PCR. Results: IR was associated with decreased muscle hypertrophy. Overload increased HSP27 phosphorylation in both the LZ and OZ rats at day 7 but only in the LZ at day 21. IR was associated with diminished overload induced MAPK phosphorylation and decreased expression of miR-1 and miR133. Overload decreased mir-1 levels in both the LZ and OZ but to a greater extent in the LZ animals. Conclusion: These results suggest that alterations in the regulation of HSPs, MAPKs and miRNA may be associated with the diminished hypertrophy of IR muscle

Cerium oxide nanoparticles attenuate monocrotaline induced right ventricular hypertrophy following pulmonary arterial hypertension

© 2014 Elsevier Ltd. Cerium oxide (CeO \u3c inf\u3e 2 ) nanoparticles have been posited to exhibit potent anti-oxidant activity which may allow for the use of these materials in biomedical applications. Herein, we investigate whether CeO \u3c inf\u3e 2 nanoparticle administration can diminish right ventricular (RV) hypertrophy following four weeks of monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH). Male Sprague Dawley rats were randomly divided into three groups: control, MCT only (60 mg/kg), or MCT + CeO \u3c inf\u3e 2 nanoparticle treatment (60 mg/kg; 0.1 mg/kg). Compared to the control group, the RV weight to body weight ratio was 45% and 22% higher in the MCT and MCT + CeO \u3c inf\u3e 2 groups, respectively (p \u3c 0.05). Doppler echocardiography demonstrated that CeO \u3c inf\u3e 2 nanoparticle treatment attenuated monocrotaline-induced changes in pulmonary flow and RV wall thickness. Paralleling these changes in cardiac function, CeO \u3c inf\u3e 2 nanoparticle treatment also diminished MCT-induced increases in right ventricular (RV) cardiomyocyte cross sectional area, β-myosin heavy chain, fibronectin expression, protein nitrosylation, protein carbonylation and cardiac superoxide levels. These changes with treatment were accompanied by a decrease in the ratio of Bax/Bcl2, diminished caspase-3 activation and reduction in serum inflammatory markers. Taken together, these data suggest that CeO \u3c inf\u3e 2 nanoparticle administration may attenuate the hypertrophic response of the heart following PAH

Cerium oxide nanoparticles attenuate monocrotaline induced right ventricular hypertrophy following pulmonary arterial hypertension

Cerium oxide (CeO(2)) nanoparticles have been posited to exhibit potent anti-oxidant activity which may allow for the use of these materials in biomedical applications. Herein, we investigate whether CeO(2) nanoparticle administration can diminish right ventricular (RV) hypertrophy following four weeks of monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH). Male Sprague Dawley rats were randomly divided into three groups: control, MCT only (60 mg/kg), or MCT + CeO(2) nanoparticle treatment (60 mg/kg; 0.1 mg/kg). Compared to the control group, the RV weight to body weight ratio was 45% and 22% higher in the MCT and MCT + CeO(2) groups, respectively (p < 0.05). Doppler echocardiography demonstrated that CeO(2) nanoparticle treatment attenuated monocrotaline-induced changes in pulmonary flow and RV wall thickness. Paralleling these changes in cardiac function, CeO(2) nanoparticle treatment also diminished MCT-induced increases in right ventricular (RV) cardiomyocyte cross sectional area, β-myosin heavy chain, fibronectin expression, protein nitrosylation, protein carbonylation and cardiac superoxide levels. These changes with treatment were accompanied by a decrease in the ratio of Bax/Bcl2, diminished caspase-3 activation and reduction in serum inflammatory markers. Taken together, these data suggest that CeO(2) nanoparticle administration may attenuate the hypertrophic response of the heart following PAH

Biomarkers of nanomaterial exposure and effect: current status

Recent advances in nanotechnology have induced a widespread production and application of nanomaterials. As a consequence, an increasing number of workers are expected to undergo exposure to these xenobiotics, while the possible hazards to their health remain not being completely understood. In this context, biological monitoring may play a key role not only to identify potential hazards from and to evaluate occupational exposure to nanomaterials, but also to detect their early biological effects to better assess and manage risks of exposure in respect of the health of workers. Therefore, the aim of this review is to provide a critical evaluation of potential biomarkers of nanomaterial exposure and effect investigated in human and animal studies. Concerning exposure biomarkers, internal dose of metallic or metal oxide nanoparticle exposure may be assessed measuring the elemental metallic content in blood or urine or other biological materials, whereas specific molecules may be carefully evaluated in target tissues as possible biomarkers of biologically effective dose. Oxidative stress biomarkers, such as 8-hydroxy-deoxy-guanosine, genotoxicity biomarkers, and inflammatory response indicators may also be useful, although not specific, as biomarkers of nanomaterial early adverse health effects. Finally, potential biomarkers from \u201comic\u201d technologies appear to be quite innovative and greatly relevant, although mechanistic, ethical, and practical issues should all be resolved before their routine application in occupational settings could be implemented. Although all these findings are interesting, they point out the need for further research to identify and possibly validate sensitive and specific biomarkers of exposure and effect, suitable for future use in occupational biomonitoring programs. A valuable contribution may derive from the studies investigating the biological behavior of nanomaterials and the factors influencing their toxicokinetics and reactivity. In this context, the application of the most recent advances in analytical chemistry and biochemistry to the biological monitoring of nanomaterial exposure may be also useful to detect and define patterns and mechanisms of early nanospecific biochemical alterations