BPB Reports

2021 - Vol. 4

2021 - Vol. 4

Regular Article
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.

Regular Article
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.

Effect of Cadmium on the Expression of ABCB1 Transporter in Human Proximal Tubular Cells Vol.4, No.2, p.74-77
Chikage Mori , Jin-Yong Lee , Maki Tokumoto , Masahiko Satoh
Received: March 15, 2021
Accepted: April 01, 2021
Released: April 20, 2021
Abstract Full Text PDF[1M]

Cadmium (Cd) is an ecotoxic heavy metal that predominantly causes renal failure. Proximal tubular cell damage is typical of chronic Cd toxicity. Proximal tubular cells play important roles in maintaining a stable balance of body chemicals through the functions of various transporters. ABC transporter subfamily B member 1 [ABCB1; also called MDR1 (multiple drug resistance 1)], one of the ATP binding cassette (ABC) multidrug efflux transporters, is expressed in the proximal tubular epithelium and is involved in the extracellular clearance of various chemicals. In this study, we demonstrate that Cd significantly increases the levels of ABCB1 mRNA and P-glycoprotein protein (the ABCB1 gene product) in the HK-2 human proximal tubular cells. Our results suggest that Cd affects the transportation function in the proximal tubules. However, ABCB1 knockdown did not affect Cd toxicity in the HK-2 cells. Therefore, the Cd-induced increase in ABCB1 may affect the transportation function in the kidney but not the Cd toxicity.

Time-Dependent Changes in the Gene Expression Levels in the Mouse Kidney by Long-Term Exposure to Cadmium Vol.4, No.2, p.69-73
Jin-Yong Lee , Chikage Mori , Maki Tokumoto , Masahiko Satoh
Received: February 16, 2021
Accepted: March 10, 2021
Released: April 12, 2021
Abstract Full Text PDF[1M]

Cadmium (Cd) is an environmental hazardous heavy metal that causes renal dysfunction triggered by its toxicity to proximal tubular cells. Our previous study demonstrated that Cd changed the activities of various transcription factors (TFs) in the mouse kidney. In this study, we investigated whether long-term exposure to Cd affected the expression levels of downstream genes of these TFs. C57BL/6J female mice were fed chow containing 300 ppm Cd for 12 months. After 4, 8, and 12 months of Cd exposure, total RNA was extracted from the mouse kidney. The results confirmed that Cd exposure dramatically increased the expression of metallothionein-2 (Mt2) in the mouse kidney. Cd exposure increased the mRNA levels of Slc13a1, Vegfa, and Vegfb among the downstream genes regulated by Cd-activated TFs. Thy1 expression was decreased by Cd exposure, even though the upstream TF was activated by Cd. Furthermore, Cd exposure decreased the mRNA levels of Agtrap, Tert, Fgfr4, Foxq1, Abcb1b, Cd274, Pck1, and Egr1 among the downstream genes regulated by Cd-suppressed TFs. The expression of Pklr increased at 4-month Cd exposure, but decreased at 12-month exposure. Although our previous study indicated Cd exposure suppressed the retinoic acid receptor TF in the mouse kidney, in the present study, it was found that the downstream gene Tnfrsf10b was up-regulated by Cd exposure. For many of the genes whose expressions were affected by long-term Cd exposure, the relationship with Cd renal toxicity has not been reported so far. Our results may provide useful clues into the molecular mechanism of Cd renal toxicity.

Regular Article
Extracellular Adenosine Induces IL-6 Production through Activation of A2B Receptor and Epidermal Growth Factor Receptor in Human Keratinocyte HaCaT Cells Vol.4, No.2, p.64-68
Ken Watanabe , Sei-ichi Tanuma , Mitsutoshi Tsukimoto
Received: January 12, 2021
Accepted: March 15, 2021
Released: March 25, 2021
Abstract Full Text PDF[1M]

Epidermal cells produce cytokines as a part of the body’s response to various external stimuli. Though extracellular ATP-induced activation of P2 receptors is involved in cytokine production in epidermal cells, it is not known whether activation of P1 receptors by extracellular adenosine leads to IL-6 production in epidermal cells. Here, we show that activation of adenosine A2B receptor induces IL-6 production via phosphorylation of epidermal growth factor receptor (EGFR) in human keratinocyte HaCaT cells. We found that treatment of HaCaT cells with 100 μM adenosine or with A2B receptor-specific agonist BAY60-6583 induced IL-6 production, and the production of IL-6 was suppressed by pretreatment with A2B receptor-specific antagonist PSB603. Adenosine- induced IL-6 production was also suppressed by A2B receptor knockdown. In addition, adenosine- and BAY60-6583-induced IL-6 production was suppressed by treatment with EGFR antagonist AG1478. Furthermore, adenosine and BAY60-6583 induced EGFR phosphorylation, and this phosphorylation was suppressed by A2B receptor knockdown. Thus, our data indicate that the A2B receptor-EGFR pathway has a role in IL-6 production. This in turn suggests that extracellular adenosine is involved in skin inflammation.

Implication of NF-κB Activation on Ozone-Induced HO-1 Activation Vol.4, No.2, p.59-63
Sumihito Togi , Misa Togi , Satoshi Nagashima , Yuichi Kitai , Ryuta Muromoto , Jun-ichi Kashiwakura , Toshiaki Miura , Tadashi Matsuda
Received: February 05, 2021
Accepted: March 09, 2021
Released: March 25, 2021
Abstract Full Text PDF[2M]

The controlled and moderate oxidative stress such as ozone induces both inflammatory and anti-inflammatory response. This balance is important for homeostasis of living organisms. Furthermore, it has been shown that this conflict response is mainly regulated by two transcriptional factors, nuclear transcriptional factor κB (NF-κB) and nuclear factor erythroid 2-related factor 2 (Nrf2). NF-κB is involved in inflammatory responses by regulating expression of cyclooxygenase-2 (COX-2) and various inflammatory cytokines while Nrf2 is involved in anti-inflammatory responses by controlling expression of numerous antioxidant enzymes such as heme oxygenase- 1 (HO-1). We here demonstrate the molecular mechanisms of the crosstalk between NF-κB and Nrf2 activation during the moderate oxidative stress induced by ozone. We first confirmed the activation of NF-κB and Nrf2 signaling during the moderate oxidative stress in HeLa cells. Induction of NF-κB-mediated COX-2 mRNA expression was observed at the early phase after stimulation (30-60 min after ozone treatment). However, induction of HO-1 mRNA expression was observed at the late phase of stimulation (6 h after stimulation). To reveal the crosstalk between NF-κB and Nrf2, we tested whether reduction of NF-κB expression affects ozone-induced Nrf2 activation by knocking down of NF-κB in HeLa cells. Importantly, the HO-1 induction by ozone was remarkably decreased by a reduction in NF-κB expression. These results suggest that the moderate oxidative stress by ozone initially induces NF-κB activation, and this NF-κB activation is required for HO-1 induction at the late phase of the moderate stress.

Relationship Between Affinity of Kn2-7 to CpG DNA and the Ability of Kn2-7 to Enhance Cellular Uptake of CpG DNA by RAW264.7 Cells Vol.4, No.2, p.55-58
Saeka Nishihara , Mayu Wakita , Kiyoshi Kawasaki
Received: January 27, 2021
Accepted: February 13, 2021
Released: March 18, 2021
Abstract Full Text PDF[1M]

Some α-helical antimicrobial peptides enhance the activation of immune cells induced by the recognition of DNA containing unmethylated cytosine-guanine motifs (CpG DNA). We recently found that an α-helical antimicrobial peptide FIKRIARLLRKIF, known as Kn2-7, increased CpG DNA-dependent responses in mouse macrophage- like RAW264.7 cells, and we also found that enhanced cellular uptake of CpG DNA by Kn2-7 was necessary but insufficient to augment CpG DNA-dependent responses. In this study, we clarified the relationship between the affinity of Kn2-7 to CpG DNA and the ability of Kn2-7 to enhance cellular uptake of DNA. Electrophoretic mobility analysis on a polyacrylamide gel revealed that Kn2-7 binds to CpG DNA more effectively than Kn2-7RA in which arginine residues of Kn2-7 were substituted with alanine residues, and also found that Kn2-7 binds to CpG DNA less effectively than Kn2-7KR in which lysine residues of Kn2-7 were substituted with arginine residues. The DNA-binding abilities of Kn2-7, Kn2-7RA, and Kn2-7KR correlated well with their abilities to enhance the cellular uptake of CpG DNA. In contrast, Kn2-7LA in which leucine residues of Kn2-7 were substituted with alanine residues exhibited a similar DNA-binding ability to Kn2-7, but it did not enhance cellular uptake of CpG DNA. Our results indicate that affinity to DNA is necessary for the ability of Kn2-7 to enhance cellular uptake of CpG DNA, but hydrophobicity of Kn2-7 is also necessary for the enhancement of cellular uptake.

Regular Article
Methionine is a Key Regulator in the Onset of Atopic Dermatitis in NC/Nga Mice Vol.4, No.1, p.47-54
Takayuki Koga , Fuka Hirayama , Tomomitsu Satoh , Yuji Ishii , Nobuhiro Kashige , Makoto Hiromura , Fumio Soeda , Akihisa Toda
Received: October 30, 2020
Accepted: January 23, 2021
Released: February 10, 2021
Abstract Full Text PDF[1M]

Atopic dermatitis (AD) is a skin disorder that presents with itching and scratching and frequently progresses to a chronic state. AD often develops in patients with an individual or family history of allergic diseases. In addition, AD may develop in patients exposed to environmental stimuli such as air pollutants or dust. However, there can be differences in the magnitude of symptoms between patients even with the same genetic background or exposure to similar environmental conditions. NC/Nga mice have been used as a model for AD. They show AD-like symptoms in an age-dependent manner, even in the absence of AD-inducing agents. In addition, similar to humans, the magnitude of AD symptoms in this model varies between individual mice. However, the mechanisms underlying these differences are unclear. In addition, little is known about the relationship between AD skin symptoms and other organs and tissues. Here, we performed a metabolome analysis on sera from NC/Nga mice to identify factors potentially related to the severity of AD symptoms. The analysis showed a correlation between reduced serum methionine levels and increased severity of AD. In addition, treatment with excess methionine before the onset of AD symptoms suppressed the development of AD. In contrast, administration of methionine after the onset of AD symptoms did not. Importantly, cysteine and taurine, irreversible metabolites of methionine, did not suppress AD development. These results show that methionine, but not its metabolites, is a key factor in the onset, rather than the development of AD.

Browning Effect of Brominated Flame Retardant, TBBP-A, on Undifferentiated Adipocytes Vol.4, No.1, p.41-46
Masahiro Yamasaki , Shinya Hasegawa , Masahiko Imai , Tetsuya Fukui , Noriko Takahashi
Received: December 19, 2020
Accepted: January 27, 2021
Released: February 08, 2021
Abstract Full Text PDF[2M]

Recent studies have suggested that exposure to brominated flame retardants (BFR) may play a pivotal role in the development of high-fat diet-induced obesity and metabolic disorders in the liver. Ketone bodies produced by β-oxidation are utilized by acetoacetyl-CoA synthetase (AACS), a cytosolic ketone body-utilizing enzyme. Previously, we reported that the gene expression of AACS is upregulated in high-fat diet-induced obesity. Here, we examined the effects of BFR, tetrabromobisphenol A (TBBP-A), on gene expression in adipocyte cell line (ST-13). Treatment of differentiated cells with TBBP-A for 48 h did not have any remarkable effects on lipid accumulation and mRNA expression of AACS, PPAR-γ, SCOT, and FAS, whereas in undifferentiated cells, mRNA expression of for the lipid and ketone body utilizing-factors (AACS, perilipin-1, and FAS) and brown adipose tissue (BAT) related factors (UCPs, PRDM16, CIDEA, and LSD-1) was upregulated. These observations suggest that TBBP-A may dysregulate lipid metabolism in undifferentiated adipocytes during ketone body utilization via AACS.

Inhibitory Effect of Anionic Uremic Toxins and Creatinine on the Renal Transport of Methotrexate in Rats Vol.4, No.1, p.36-40
Yuichi Ichimura , Natsumi Kudoh , Shiho Ito , Masako Oda , Hiroshi Saitoh
Received: June 26, 2020
Accepted: January 25, 2021
Released: February 08, 2021
Abstract Full Text PDF[846K]

Various substances called uremic toxins (UTs) accumulate in the blood of patients with chronic kidney disease (CKD) and induce unfavorable effects on the body. It has been reported that some kinds of UTs are excreted extensively in the urine via renal transporters. This characteristic of UTs often becomes a factor for influencing pharmacokinetics of drugs in CKD patients. Even now, however, information on the interactions between UTs and drugs in the process of renal excretion remains limited. Methotrexate (MTX) is widely used for the treatment of rheumatoid and leukemia. It is known that MTX is predominantly excreted in the urine and that this process is mediated by organic anion transporters (OATs). In this study, we investigated the inhibitory effects of two anionic UTs, indoxyl sulfate (IS) and indoleacetic acid (IA), as well as creatinine (Cr) on the renal transport of methotrexate (MTX) using rat renal cortical slices. IS and IA, both substrates for OATs, significantly inhibited the uptake of 50 μM MTX in a concentration-dependent manner at 0.1 mM and 1 mM. In the presence of 1 mM Cr, a cationic guanidino compound, the uptake of MTX was significantly decreased, indicating that Cr is capable of interfering with OATs. In conclusion, it was suggested that the urinary excretion of MTX is extensively suppressed through interactions via OATs when IS, IA, and Cr exist a high concentrations in the blood of CKD patients.

Regular Article
Rab7-Dependent Endocytic Pathways Play an Important Role in Nutrient Absorption during Pre-Weaning Growth Vol.4, No.1, p.27-35
Aya Takimoto
Received: December 04, 2020
Accepted: December 27, 2020
Released: February 08, 2021
Abstract Full Text PDF[17M]

Enterocytes in neonatal rodent endocytose milk materials as macromolecule and digest them into small nutrient molecules. Bulk endocytic membrane flow sustaining nutrient uptake inevitably brings the plasma membrane into large lysosomes, as known as supranuclear vesicles or apical vacuoles which exhibit a unique morphology in infant enterocytes. Endocytic delivery to the large vacuoles required the function of Rab7 GTPase. The Rab7-deficient neonatal enterocytes became filled with abnormal gigantic vacuoles as they migrated from the intervillus pocket to the distal region of the villi and they became defective in taking up macromolecules. Infant animals lacking Rab7 in enterocytes exhibited growth retardation. These results showed that the Rab7-dependent endocytic pathways play an important role in nutrient absorption during pre-weaning growth.

Regular Article
Relationship Between Serum Potassium, Magnesium, and Calcium in Patients Receiving Cetuximab Therapy Vol.4, No.1, p.22-26
Kaito Yamashiro , Atsushi Hirata , Ryosuke Ota , Fumihiko Ogata , Takehiro Nakamura , Naohito Kawasaki
Received: January 09, 2021
Accepted: January 20, 2021
Released: February 04, 2021
Abstract Full Text PDF[1M]

Cetuximab (Cmab) is known to cause electrolyte abnormalities, including hypomagnesemia, hypokalemia, and hypocalcemia. However, little is known about differences in these electrolyte levels between hypomagnesemia and non-hypomagnesemia group in patients receiving Cmab. Therefore, the aim of this study was to clarify the relationship between these serum electrolyte levels in patients undergoing Cmab therapy. A retrospective study was conducted to investigate patients for advanced or recurrent colorectal cancer and head and neck cancer, treated with a regimen composed of Cmab from 2012 to 2020 at the Kindai University Nara Hospital. A total of 113 patients were identified from the medical records, and 24 patients who met the inclusion criteria were enrolled in this study. In the non-hypomagnesemia group, significant positively correlations were observed between calcium and potassium (p = 0.018), between potassium and magnesium (p = 0.008), and between magnesium and calcium (p = 0.038). Simultaneously, in the hypomagnesemia group, no statistically significant correlations were recorded between these electrolytes. The incidences of hypokalemia, hypomagnesemia, and hypocalcemia were 25.0% (6/24), 29.2% (7/24), and 25.0% (6/24), respectively. Additionally, the onset of hypokalemia was significantly associated with the onset of hypocalcemia (p = 0.009). These data suggest that it is important to monitor these electrolyte levels, especially in patients who received Cmab with combination therapy.

Fiber-Knob Region of Adenovirus Type 5 Vector Promotes Migration of A549 Cells Vol.4, No.1, p.17-21
Junpei Kano , Naoya Koizumi , Airi Terada , Ayana Matsuoka , Takamasa Hirai , Tetsuya Nomura , Hiroyuki Mizuguchi , Naoki Utoguchi
Received: November 05, 2020
Accepted: January 11, 2021
Released: February 02, 2021
Abstract Full Text PDF[1M]

Adenoviral vectors based on adenovirus type 5 (Ad5) are commonly used for gene therapy. The Ad5 fiber-knob region primarily interacts with the coxsackievirus and adenovirus receptor (CAR). Reportedly, when stimulated, this receptor participates in the regulation of cell-to-cell adhesion and cell migration. In oncogene therapy, cell migration can have adverse effects by promoting metastasis and infiltration. Alternatively, cell migration may enhance the therapeutic effect of gene therapy by promoting the healing of injured tissues. However, the effect of binding of the Ad fiber-knob region to CAR of target cells has not been investigated in detail. Therefore, the aim of the present study was to investigate the effects of the Ad5 vectors on cell migration with the use of wound healing and migration assays. The results showed that infection with the Ad5 vectors promoted the migration of A549 cells, as determined quantifiably. Furthermore, when the Ad5 fiber-knob protein was applied to A549 cells, the same results were obtained. Together, the results revealed that binding of the Ad fiber-knob protein to CAR causes cell migration as a functional change in target cells. Studying the effect of the Ad fiber-knob protein will lead to the development of a gene transfer vector with greater safety and therapeutic effects.

Regular Article
Comparative Study of Different Epidermal Growth Factor Receptor (EGFR)-Tyrosine Kinase Inhibitors Affecting Lung Cancer Cell Lines Stably Overexpressing EGFR Mutations Vol.4, No.1, p.12-16
Tomohiro Ariyama , Yuichiro Kanno , Sonomi Takizawa , Kiyomitsu Nemoto , Toshihiro Ishii
Received: October 15, 2020
Accepted: January 05, 2021
Released: January 28, 2021
Abstract Full Text PDF[1M]

Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are effective drugs against non-small cell lung cancer (NSCLC) cells harboring common EGFR mutations such as in-frame exon 19 deletions (Del19) and the exon 21 L858R point mutations (L858R). However, currently used EGFR-TKIs are less effective against cells showing uncommon EGFR mutations. Because there is less information available on the sensitivities of the uncommon EGFR mutations, it is important to evaluate the effect of EGFR-TKIs on uncommon mutations. In this study, we sought to establish H1299 NSCLC cell lines stably expressing mutated EGFRs having Del18, G719S, or L861Q that are uncommon mutations as well as Del19 or L858R common mutations, and evaluated whether these cell lines could be applied as a prediction system for the therapeutic effects of EGFR-TKIs. In fact, the levels of phosphorylated EGFR in these cell lines were assessed after treatment with various EGFR-TKIs (4 approved and 4 unapproved drugs). Gefitinib, erlotinib, afatinib, and osimertinib, approved drugs, were effective against Del19, L858R, and L861Q mutations. However, these EGFR-TKIs were less effective against G719S and Del18 mutations. The unapproved drugs neratinib and poziotinib were effective against Del19, L858R, Del18, and L861Q mutations. Interestingly, canertinib and sapitinib had effects against Del19, Del18, and L861Q mutations and no effect against L858R mutation. These results indicate that the established cell lines are suitable for assessing the effects of the EGFR-TKIs on EGFR mutations, including uncommon mutations, and that some of the EGFR-TKIs used are also effective against uncommon mutations.

Regular Article
Sorghum (Sorghum bicolor (L.) Moench) Extract Enhances Thiazolidinedione-Induced 3T3-L1 Preadipocyte Differentiation but Inhibits Adipogenic Genes Vol.4, No.1, p.6-11
Makoto Sakurai , Ikumi Aizu , Marina Tonosaki , Yuko Oba , Mei Nagata , Katsuyoshi Kamiie , Atsuko Masumi
Received: November 20, 2020
Accepted: January 17, 2021
Released: January 28, 2021
Abstract Full Text PDF[1M]

Sorghum bicolor (L.) Moench is known as a healthful food. We examined whether a water-soluble sorghum extract (SE) from S. bicolor has an anti-diabetic effect through a mechanism that improves insulin sensitivity or anti-adipogenesis. Although the treatment of SE did not affect the adipogenesis of 3T3-L1 adipocytes induced by isobutyl methylxanthine/dexamethasone/insulin (MDI), it significantly enhanced MDI/thiazolidinedione (TZD)-induced adipogenesis in 3T3-L1 adipocyte differentiation. Real-time polymerase chain reaction analysis showed that treatment with SE reduced the expression of adiponectin, adipocyte protein 2 (aP2), and resistin in 3T3-L1 adipocyte cells. SE suppressed the expression of transcription factors, peroxisome proliferator-activated receptor γ (PPARγ), and CCAAT enhancer-binding protein α in both MDI- and MDI/TZDs-treated 3T3-L1 adipocytes. SE treatment reduced tumor necrosis factor α protein in cell lysates from MDI-induced 3T3-L1 adipocytes but not those induced by MDI/TZD. Our results suggest that SE can serve as an effective food source that improves insulin sensitivity and an anti-obesity agent.

Regular Article
Ropinirole Prevents Light-Induced Retinal Photoreceptor Damage in Mice Vol.4, No.1, p.1-5
Miruto Tanaka , Yuki Inoue , Yuta Yoshino , Yoshiki Kuse , Norifumi Tanida , Koichi Takahashi , Yohei Miyamoto , Hideaki Hara
Received: November 25, 2020
Accepted: January 08, 2021
Released: January 21, 2021
Abstract Full Text PDF[3M]

Photoreceptor cell death leads to blindness in dry age-related macular degeneration (AMD) patients. However, no current therapy exists to treat drug for dry AMD patients. Here, we investigated the neuroprotective effects of ropinirole, a dopamine agonist used to treat Parkinson’s disease, in vitro and in vivo murine dry AMD models. Ropinirole prevented photoreceptor cell death induced by excessive light exposure in vitro. Next, we exposed mice to intensive white fluorescent light, performed morphological analysis of the outer nuclear layer (ONL), and examined electroretinogram (ERG) recordings. Although light exposure reduced ONL thickness and ERG amplitudes, the oral administration of ropinirole improved ONL thickness and a- and b-wave amplitudes, similar to pramipexole treatment. Furthermore, the continuous administration of ropinirole using an osmotic pump attenuated the decrease in retinal thickness induced by chronic light exposure. These findings indicated that ropinirole represents a novel candidate drug for dry AMD treatment.