Biochemical and biophysical research communications
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Biochem. Biophys. Res. Commun. · Aug 2010
Role of different nitric oxide synthase isoforms in a murine model of acute lung injury and sepsis.
Excessive production of nitric oxide (NO) by NO synthase (NOS) with subsequent formation of peroxynitrite and poly(adenosine diphosphate ribose) is critically implemented in the pathophysiology of acute lung injury and sepsis. To elucidate the roles of different isoforms of NOS, we tested the effects of non-selective NOS inhibition and neuronal NOS (nNOS)- and inducible NOS (iNOS)-gene deficiency on the pulmonary oxidative and nitrosative stress reaction in a murine sepsis model. The injury was induced by four sets of cotton smoke using an inhalation chamber and subsequent intranasal administration of live Pseudomonas aeruginosa (3.2x10(7) colony-forming units). ⋯ Treatment with a non-selective NOS inhibitor failed to reduce the oxidative and nitrosative stress reaction to the same extent and even tended to increase mortality. In conclusion, the current study demonstrates that both nNOS and iNOS are partially responsible for the pulmonary oxidative and nitrosative stress reaction in this model. Future studies should investigate the effects of specific pharmacological inhibition of nNOS and iNOS at different time points during the disease process.
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Biochem. Biophys. Res. Commun. · Aug 2010
Tanshinone IIA improves impaired nerve functions in experimental diabetic rats.
Diabetic neuropathy is one of the most common complications in diabetes mellitus. Thus far, effective therapeutic agents for restoring the impaired motor and sensory nerve functions in diabetic neuropathy are still lacking. The antioxidant and neuroprotective properties of tanshinone IIA make it a promising candidate for the treatment of diabetic neuropathy. ⋯ We found that tanshinone IIA was capable of restoring diabetes-induced deficit in nerve functions (MNCV and NBF), and impairment in thermal and mechanical nociceptive capability. In addition, tanshinone IIA significantly increased the serum total antioxidant capability, improved the activities of Na(+),K(+)ATPase, increased the levels of SOD and catalase, and reduced the MDA level in sciatic nerves in diabetic rats. All the findings indicate the beneficial effect of tanshinone IIA on impaired nerve functions and raise the possibility of developing tanshinone IIA as a therapeutic agent for diabetic neuropathy.
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Biochem. Biophys. Res. Commun. · Jul 2010
Establishment of sandwich ELISA for soluble alpha-Klotho measurement: Age-dependent change of soluble alpha-Klotho levels in healthy subjects.
Alpha-Klotho (alphaKl) regulates mineral metabolism such as calcium ion (Ca(2+)) and inorganic phosphate (Pi) in circulation. Defects in mice result in clinical features resembling disorders found in human aging. Although the importance of transmembrane-type alphaKl has been demonstrated, less is known regarding the physiological importance of soluble-type alphaKl (salphaKl) in circulation. ⋯ We established a detection system to measure human serum salphaKl for the first time. Age, Ca and Pi seem to influence serum salphaKl levels in a normal population. This detection system should be an excellent tool for investigating salphaKl functions in mineral metabolism.
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Biochem. Biophys. Res. Commun. · Jul 2010
Nifedipine inhibits advanced glycation end products (AGEs) and their receptor (RAGE) interaction-mediated proximal tubular cell injury via peroxisome proliferator-activated receptor-gamma activation.
There is a growing body of evidence that advanced glycation end products (AGEs) and their receptor (RAGE) interaction evokes oxidative stress generation and subsequently elicits inflammatory and fibrogenic reactions, thereby contributing to the development and progression of diabetic nephropathy. We have previously found that nifedipine, a calcium-channel blocker (CCB), inhibits the AGE-induced mesangial cell damage in vitro. However, effects of nifedipine on proximal tubular cell injury remain unknown. ⋯ GW9662 treatment alone was found to increase RAGE mRNA levels in tubular cells. Further, nifedipine inhibited the AGE-induced reactive oxygen species generation, NF-kappaB activation and increases in intercellular adhesion molecule-1 and transforming growth factor-beta gene expression in tubular cells, all of which were blocked by GW9662. Our present study provides a unique beneficial aspect of nifedipine on diabetic nephropathy; it could work as an anti-oxidative and anti-inflammatory agent against AGEs in tubular cells by suppressing RAGE expression via PPARgamma activation.
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Biochem. Biophys. Res. Commun. · Jun 2010
alpha-Tocopherol attenuates the cytotoxic effect of delta-tocotrienol in human colorectal adenocarcinoma cells.
Recent studies have demonstrated that tocotrienol (T3) is superior to tocopherol (Toc) for cancer chemoprevention. However, there is little information on whether Toc influences the anticancer property of T3. ⋯ Furthermore, coadministration of alpha-Toc decreased delta-T3 uptake into DLD-1 cells in a dose-dependent manner. These results indicate that alpha-Toc is not only less cytotoxic to cancer cells, but it also reduces the cytotoxicity of delta-T3 by inhibiting its cellular uptake.