2021 - Vol. 4
|Suramin Inhibits Mitochondrial ADP/ATP Carrier, Not Only from the Cytosolic Side But Also from the Matrix Side, of the Mitochondrial Inner Membrane||Vol.4, No.3, p.92-97|
|Yoshinobu Fujiwara , Takeshi Ito , Atsumi Toiyama , Takenori Yamamoto , Naoshi Yamazaki , Mitsuru Shindo , Yasuo Shinohara|
|Received: May 12, 2021|
|Accepted: June 01, 2021|
|Released: June 17, 2021|
|Abstract||Full Text PDF[1M]|
Suramin was earlier reported to show inhibitory effects on the mitochondrial ADP/ATP carrier. However, two important questions, i) whether it shows a specific inhibition of the ADP/ATP carrier when applied to isolated mitochondria, and ii) whether it inhibits the mitochondrial ADP/ATP carrier only from the cytosolic side or from the matrix side, as has been observed with its canonical inhibitors of carboxyatractyloside or bongkrekic acid, remain to be answered. In the present study, we sought exact answers to these questions. As for the first question, suramin showed certain inhibitory effects on the mitochondrial respiratory chain; and at a concentration of 25 μM it showed strong inhibition of the mitochondrial ADP/ATP carrier. This property was due to its weaker inhibitory effects on the mitochondrial ADP/ATP carrier than those of carboxyatractyloside or bongkrekic acid. As for the second question, suramin inhibited the ADP/ATP carrier from both sides of the mitochondrial inner membrane. Thus, suramin was concluded to be utilizable as a new type of inhibitor for the ADP/ATP carrier; but we must pay attention to its side-effects, especially when it is applied to whole mitochondria.
|Increased Expression of Heparan Sulfate 6-O-Sulfotransferase-2 Promotes Collagen Production in Cardiac Myofibroblasts||Vol.4, No.3, p.85-91|
|Kotaro Kasai , Yuma Horii , Takanori Hironaka , Kyosuke Mae , Tomoyuki Ueno , Akiomi Nagasaka , Michio Nakaya|
|Received: April 22, 2021|
|Accepted: May 14, 2021|
|Released: June 07, 2021|
|Abstract||Full Text PDF[1M]|
Fibrosis is defined as the excessive accumulation of extracellular matrix (ECM) proteins. These excessive ECM proteins are produced by myofibroblasts, which are differentiated mainly from resident fibroblasts in response to tissue injury. In addition to the ECM proteins, the amounts of heparan sulfate, one of the sugar chains, and the proteoglycans attached with heparan sulfate chains are reported to be increased in the fibrotic tissues. However, the contribution of heparan sulfate and heparan sulfate proteoglycans to the development of fibrosis remains unclear. In this study, we found that heparan sulfate 6-O-sulfotransferase-2 (Hs6st2), a type of heparan sulfate transferase, is remarkably induced during fibrosis in the heart, liver, and kidney of mice. We also demonstrated that Hs6st2 was specifically expressed in myofibroblasts of mice with cardiac and liver fibrosis. Hs6st2 knockdown in cardiac myofibroblasts reduced the mRNA expression of fibrosis-related factors, such as Collagen1a1. In summary, this study revealed that Hs6st2 is specifically expressed in myofibroblasts in fibrotic tissues, promotes fibrosis, and can be a good target for the treatment for fibrosis.
|Verification of MA-T Safety and Efficacy Against Pathogens Including SARS-CoV-2||Vol.4, No.3, p.78-84|
|Takekatsu Shibata , Ryuta Urakawa , Chikako Ono , Yukihiro Akeda , Takayoshi Sakai , Shigeto Hamaguchi , Kiyoto Takamori , Tsuyoshi Inoue , Kazunori Tomono , Kiyoshi Konishi , Yoshiharu Matsuura|
|Received: March 17, 2021|
|Accepted: May 11, 2021|
|Released: May 26, 2021|
|Abstract||Full Text PDF[731K]|
Matching transformation system (MA-T) is an on-demand aqueous chlorine dioxide solution. It is a disinfectant developed to maximize the safety of chlorine dioxide radical in water and its effectiveness against various microorganisms. In this study, we examined the safety and effectiveness of MA-T for its use in various infectious disease countermeasures, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and consider if MA-T can be implemented in society. To validate the safety of MA-T, we conducted safety tests and efficacy tests in accordance with GLP-based reliability criteria. To evaluate the efficacy, minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) confirmation tests against various bacteria, and virus inactivation test against various viruses including SARS-CoV-2 by TCID50 method were performed. The results of safety tests showed that MA-T was at least as safe as Japanese tap water. As a result of efficacy tests for microorganisms, MA-T was effective against many bacteria. Efficacy tests for virus showed that MA-T inactivates SARS-CoV-1, Middle East respiratory syndrome coronavirus (MERS-CoV), rotavirus A (RVA), hepatitis C virus (HCV), dengue virus (DENV), and hepatitis B virus (HBV). MA-T also inactivated 99.98% of SARS-CoV-2, which is equivalent to ethanol for disinfection. MA-T has proven to be a safe and effective disinfectant. MA-T is a next-generation disinfectant that has the potential to be safer and more effective than conventional chlorine disinfectants and other disinfectants. It also proved to be an effective disinfectant against SARS-CoV-2, which is currently causing pandemic all over the world.