鰹出汁摂取がヒトの疲労に及ぼす影響の予備的検討

In many previous reports, it has been suggested the daily ingestion of dried-bonito broth (DBB) might improve various symptoms related to fatigue. To (re)confirm these effects of DBB, 24 healthy young female subjects ingested DBB for 40 or 42 days. Measurement of fatigue score on the profile of mood states (POMS) questionnaire, critical flicker-fusion frequency (CFF) and physical fitness using bicycle ergometer were performed before and after the ingestion periods. The urinary amount of 8-hydroxy-2’-deoxyguanosine (8-OH-dG) and creatinine were also measured before and after exercise stress using bicycle ergometer. Although the analysis for fatigue score on the available POMS data didn’t significantly decreased, 7 subjects with high fatigue score (more than 20 points) before the ingestion periods revealed the significant improvement of the score. Also significant increase of CFF showed the recovery from the mental fatigue by DBB ingestion. On the other hand, since the results for measurement of physical fitness and urinary 8-OH-dG level corrected with creatinine amount didn’t change significantly, we couldn’t observe the anti-fatigue effect against physical fatigue in this study. All things considered, our results suggested that the daily ingestion of DBB might show the tendency for the improvement against at least some type of fatigue

Function of the ABC Signature Sequences in the Human Multidrug Resistance Protein 1

ABSTRACT Human multidrug resistance protein 1 (MRP1) is a membrane ATP-binding cassette transporter that confers multidrug resistance to tumor cells by effluxing intracellular drugs in an ATPdependent manner. The mechanisms by which transport occurs and by which ATP hydrolysis is coupled to drug transport are not fully elucidated. In particular, the function of the signature sequences in the nucleotide binding domains (NBDs) of MRP1 is unknown. We therefore investigated the effect of mutation of the signature sequences (G771D and G1433D) and of the Walker A motifs (K684M and K1333M) in the NBDs on the 8-azido-[␣- 32 P]ATP photolabeling and 8-azido-[␣-32 P]ADP vanadate trapping of MRP1. Both mutations in the Walker A motif almost completely inhibited the labeling of the mutated NBD with 8-azido-[␣- 32 P]ATP but not the labeling of the other intact NBD. In contrast, the G771D mutation in the signature sequence of NBD1 enhanced the labeling of NBD1 but slightly decreased the labeling of NBD2. The G1433D mutation in the signature motif of NBD2 enhanced the labeling of NBD2 but did not affect the labeling of NBD1. These effects were all substrate-independent. Photolabeling of NBD2 and a very slight photolableing of NBD1 were detectable under vanadate trapping conditions with 8-azido-[␣- 32 P]ATP. Trapping at both NBD1 and NBD2 was almost completely inhibited by K684M and K1333M mutations and by the K684M/K1333M double mutation. The G771D mutation completely inhibited trapping at NBD2 and considerably inhibited trapping at NBD1. However, whereas the G1433D mutation also considerably inhibited trapping at NBD1, it only partially inhibited trapping of NBD2, and the trapping could still be enhanced by leukotriene C 4 . Our findings suggest that both signature sequences of MRP1 are involved in ATP hydrolysis and must be intact for the ATP hydrolysis and the transport by MRP1