松下会ニュース

Imafukua T*, Tanaka M*, Tokunaga K, Miyamura S, Kato H, Tanaka S, Nakano T, Hirata K, Kadowaki D, Maeda H, Matsushita K, Otagiri M, Komaba H, Fukagawa M, Watanabe H#, Maruyama T# Effect of cinacalcet on the redox status of albumin in secondary hyperparathyroidism patients receiving hemodialysis. Biol Pharm Bull. in press *equal contribution; # equal corresponding author

Abstract

Chronic kidney disease (CKD) patients with secondary hyperparathyroidism (SHPT) have an increased risk of cardiovascular disease (CVD). Cinacalcet is a calcimimetic that permits impaired endothelial functions to be recovered via inhibiting parathyroid hormone (PTH) production in SHPT patients. However, the underlying mechanism for its action remains unknown. The purpose of this study was to examine the effect of cinacalcet on the redox state of human serum albumin (HSA), a reliable marker for assessing endothelial oxidative damage in SHPT patients who were receiving hemodialysis. Cinacalcet was administered to six SHPT patients for a period of 8 weeks. After 4 weeks of treatment, cinacalcet significantly decreased the oxidized albumin ratio which is a ratio of reduced and oxidized forms of HSA via increasing reduced form of HSA. Moreover, the radical scavenging abilities of HSA that was isolated from SHPT patients were increased by cinacalcet, suggesting the recovery of the impaired vascular anti-oxidant ability. Interestingly, the oxidized albumin ratio in SHPT patients was significantly higher than that in hemodialysis patients. In addition, the changes of intact PTH levels were significantly correlated with the oxidized albumin ratio. It therefore appears that PTH may induce oxidative stress in SHPT patients. In fact, an active analogue of PTH increased the production of reactive oxygen species in human endothelial cells. Thus, cinacalcet exhibits anti-oxidative activity through its pharmacological action. Additionally, cinacalcet itself showed radical scavenging activity. In conclusion, cinacalcet improves the redox status of HSA by inhibiting PTH production and partially by inhibiting its radical scavenging action.

①Kidney360に論文が受理されました。（酸化蛋白質による腎Elovl6発現誘導と脂肪酸組成の変動が腎障害の進展に関与する）

Advanced oxidation protein products contribute to renal tubulopathy via perturbation of renal fatty acids

Tadashi Imafuku, Hiroshi Watanabe§, Takao Satoh, Takashi Matsuzaka, Tomoaki Inazumi, Hiromasa Kato, Shoma Tanaka, Yuka Nakamura, Takehiro Nakano, Kai Tokumaru, Hitoshi Maeda, Motoko Tanaka, Kazutaka Matsushita, Soken Tsuchiya, Yukihiko Sugimoto, Hitoshi Shimano, Masafumi Fukagawa, Toru Maruyama

②Bi J, Watanabe H, Fujimura R, Nishida K, Nakamura R, Oshiro S, Imafuku T, Komori H, Miyahisa M, Tanaka M, Matsushita K, Maruyama T, A downstream molecule of 1,25-dihydroxyvitamin D3, alpha-1-acid glycoprotein, protects against mouse model of renal fibrosis, Sci Rep (2018) Nov 26;8(1):17329.

③Watanabe H*#, Sugimoto R*, Ikegami K, Enoki Y, Imafuku T, Fujimura R, Bi J, Nishida K, Sakaguchi Y, Murata M, Maeda H, Hirata K, Jingami S, Ishima Y, Tanaka M, Matsushita K, Komaba H, Fukagawa M, Otagiri M, Maruyama T#. Parathyroid hormone contributes to the down-regulation of cytochrome P450 3A through the cAMP/PI3K/PKC/PKA/NF-κB signaling pathway in secondary hyperparathyroidism. Biochem Pharmacol. *equal contribution, #equal corresponding author 2017 Dec 1;145:192-201.

④Enoki Y*, Watanabe H*, Arake R, Fujimura R, Ishiodori K, Imafuku T, Nishida K, Sugimoto R, Nagao S, Miyamura S, Ishima Y, Tanaka M, Matsushita K, Komaba H, Fukagawa M, Otagiri M, Maruyama T. Potential therapeutic interventions for chronic kidney disease-associated sarcopenia via indoxyl sulfate-induced mitochondrial dysfunction. J Cachexia Sarcopenia Muscle. *equal contribution 2017 Oct;8(5):735-747.

 ⑤Enoki Y, Watanabe H, Arake R, Sugimoto R, Imafuku T, Tominaga Y, Ishima Y, Kotani S, Nakajima M, Tanaka M, Matsushita K, Fukagawa M, Otagiri M, Maruyama T. Indoxyl sulfate potentiates skeletal muscle atrophy by inducing the oxidative stress-mediated expression of myostatin and atrogin-1. Sci Rep. 6:32084 (2016)

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http://www.matusita-kai.or.jp/medical-info/office/akebono/special/

　7月21日（火）、パストラルハイム白藤での「パストラルハイムサロン」において、
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皆さん、メモを取りながら、大変熱心に聞いておられました。
講演においては、マスクや手指消毒など新型コロナ感染対策を十分行った上で開催されました。

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　2020年6月25日（木）にWeb会議で開催された
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