Estimation of radiation dose from ingested tritium in humans by administration of deuterium-labelled compounds and food

Abstract Radiation doses from organically bound tritium (OBT) in foods have been a major concern near nuclear facilities. The current dose coefficient for OBT is calculated using a standard model from the International Commission on Radiological Protection, in which some biokinetic values are not based on human metabolic data. Here, the biokinetics of ingested OBT, and radiation doses from them, were estimated by administering labelled compounds and foods to volunteers, using a deuterium (D) tracer as a substitute for tritium. After the administration of D-labelled glucose, alanine, palmitic acid, or soybean, the D/H ratios in urine were measured for up to 119 days, and the biokinetic parameter values were determined for OBT metabolism. The slow degradation rates of OBT could not be obtained, in many volunteers administered glucose and alanine. The estimated committed effective dose for 1 Bq of tritium in palmitic acid varied from 3.2 × 10–11 to 3.5 × 10–10 Sv Bq−1 among volunteers and, for those administered soybean, it varied from 1.9 × 10–11 to 1.8 × 10–10 Sv Bq−1. These results suggest that OBT, present in some ingested ingredients, gives higher doses than the current dose coefficient value of 4.2 × 10–11 Sv Bq−1

Potential roles of neuronal nitric oxide synthase and the PTEN-induced kinase 1 (PINK1)/Parkin pathway for mitochondrial protein degradation in disuse-induced soleus muscle atrophy in adult rats.

Excessive nitric oxide (NO) production and mitochondrial dysfunction can activate protein degradation in disuse-induced skeletal muscle atrophy. However, the increase in NO production in atrophied muscles remains controversial. In addition, although several studies have investigated the PTEN-induced kinase 1 (PINK1)/Parkin pathway, a mitophagy pathway, in atrophied muscle, the involvement of this pathway in soleus muscle atrophy is unclear. In this study, we investigated the involvement of neuronal nitric oxide synthase (nNOS) and the PINK1/Parkin pathway in soleus muscle atrophy induced by 14 days of hindlimb unloading (HU) in adult rats. HU lowered the weight of the soleus muscles. nNOS expression showed an increase in atrophied soleus muscles. Although HU increased malondialdehyde as oxidative modification of the protein, it decreased 6-nitrotryptophan, a marker of protein nitration. Additionally, the nitrosocysteine content and S-nitrosylated Parkin were not altered, suggesting the absence of excessive nitrosative stress after HU. The expression of PINK1 and Parkin was also unchanged, whereas the expression of heat shock protein 70 (HSP70), which is required for Parkin activity, was reduced in atrophied soleus muscles. Moreover, we observed accumulation and reduced ubiquitination of high molecular weight mitofusin 2, which is a target of Parkin, in atrophied soleus muscles. These results indicate that excessive NO is not produced in atrophied soleus muscles despite nNOS accumulation, suggesting that excessive NO dose not mediate in soleus muscle atrophy at least after 14 days of HU. Furthermore, the PINK1/Parkin pathway may not play a role in mitophagy at this time point. In contrast, the activity of Parkin may be downregulated because of reduced HSP70 expression, which may contribute to attenuated degradation of target proteins in the atrophied soleus muscles after 14 days of HU. The present study provides new insights into the roles of nNOS and a protein degradation pathway in soleus muscle atrophy

Microcurrent electrical nerve stimulation facilitates regrowth of mouse soleus muscle

Microcurrent electrical nerve stimulation (MENS) has been used to facilitate recovery from skeletal muscle injury. However, the effects of MENS on unloading-associated atrophied skeletal muscle remain unclear. Effects of MENS on the regrowing process of unloading-associated atrophied skeletal muscle were investigated. Male C57BL/6J mice (10-week old) were randomly assigned to untreated normal recovery (C) and MENS-treated (M) groups. Mice of both groups are subjected to continuous hindlimb suspension (HS) for 2 weeks followed by 7 days of ambulation recovery. Mice in M group were treated with MENS for 60 min 1, 3, and 5 days following HS, respectively, under anesthesia. The intensity, the frequency, and the pulse width of MENS were set at 10 μA, 0.3 Hz, and 250 msec, respectively. Soleus muscles were dissected before and immediately after, 1, 3 and 7 days after HS. Soleus muscle wet weight and protein content were decreased by HS. The regrowth of atrophied soleus muscle in M group was faster than that in C group. Decrease in the reloading-induced necrosis of atrophied soleus was facilitated by MENS. Significant increases in phosphorylated levels of p70 S6 kinase and protein kinase B (Akt) in M group were observed, compared with C group. These observations are consistent with that MENS facilitated regrowth of atrophied soleus muscle. MENS may be a potential extracellular stimulus to activate the intracellular signals involved in protein synthesis

Caffeine Affects Myotube Size As Well As Regulates Protein Degradation and Protein Synthesis Pathways in C2C12 Skeletal Muscle Cells

[Background]: Caffeine has been implicated in energy metabolism regulation in skeletal muscle. However, it is unclear whether caffeine affects the regulation of skeletal muscle size. In the present study, we evaluated the effect of caffeine on muscle size as well as accompanied changes of ubiquitin–proteasome system and Akt/mammalian target of rapamycin (mTOR)/p70 s6 kinase (p70S6K) signaling. [Methods]: Differentiated C2C12 myotubes were incubated with caffeine (0, 0.1, 1.0, 3.0 mM) for 24 hours. We then estimated the protein content, myotube diameter, and the expression levels of muscle RING finger 1 (MuRF1) messenger RNA (mRNA), atrogin-1/muscle atrophy F-box (MAFbx) mRNA, K48-linked polyubiquitin, phosphorylated 5′-AMP-activated protein kinase (AMPK) α Thr172, 72-kDa heat shock protein (HSP72), HSP72 mRNA, inhibitor κBα (IκBα), phosphorylated forkhead box class O3a (FoxO3a) Ser253, myogenin mRNA, microRNA (miR)-23a, phosphorylated Akt Ser473, and phosphorylated p70S6K Thr389. [Results]: Protein content and myotube diameter were lower in myotubes treated with caffeine (≥1 mM) compared with untreated cells. The expression levels of MuRF1 and atrogin-1/MAFbx mRNA and K48-linked polyubiquitin were increased by caffeine treatment. However, phosphorylated AMPKα Thr172, HSP72 protein and mRNA, IκBα, phosphorylated FoxO3a Ser253, and miR-23a expression were not affected by caffeine treatment. Myogenin mRNA expression was upregulated in response to caffeine treatment. The expressions of phosphorylated Akt Ser473 and p70S6K Thr389 were suppressed by caffeine. [Conclusions]: Caffeine might affect muscle size by stimulating ubiquitin–proteasome system and inhibiting Akt/mTOR/p70S6K signaling, partly through an AMPK-independent mechanism