Article
Physiology
Lianguo Wang, Rachel C. Myles, I-Ju Lee, Donald M. Bers, Crystal M. Ripplinger
Summary: The study demonstrates that inhibition of SERCA can slow down SR Ca2+ reuptake, leading to an increase in the magnitude of Ca2+ alternans in cardiac cells, especially at fast pacing frequencies. Notably, the alternation of SR Ca2+ release precedes the alternation of SR Ca2+ load during rapid ventricular pacing.
FRONTIERS IN PHYSIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Paula Grenon, Gerardo R. Corradi, Guido D. Petrovich, Luciana R. Mazzitelli, Hugo P. Adamo
Summary: The study focused on the role of the arm-like domain in Spf1p P5A-ATPase, showing that it is not essential for hydrolytic activity but is needed for stabilizing the enzyme in a phosphorylation-ready conformation. The Darm mutant displayed reduced ATP hydrolysis and non-nucleotide substrate analog activity compared to the wild type enzyme.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Pharmacology & Pharmacy
Ha Thu Nguyen, Carlos Noriega Polo, Andreas Wiederkehr, Claes B. Wollheim, Kyu-Sang Park
Summary: Enhancing endoplasmic reticulum (ER) calcium uptake through activation of the sarco/endoplasmic reticulum calcium ATPase (SERCA) can improve survival and function of pancreatic ss-cells. Activation of SERCA increases insulin synthesis and exocytosis, enhances sensitivity to glucose, and improves mitochondrial bioenergetics and antioxidant capability. Targeting SERCA could be a promising therapeutic strategy for protecting ss-cells from lipotoxicity and Type 2 diabetes development.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Xuan Xiong, Xiaoqin Zhang, Yuan Zhang, Jiaqi Xie, Yuan Bian, Qinan Yin, Rongsheng Tong, Dongke Yu, Lingai Pan
Summary: This study found that TCEP exposure can cause cardiac fibrosis by inhibiting the expression of SERCA and leading to Ca2+ overload, which in turn triggers ER stress and overactive autophagy. The results reveal the important role of the Ca2+ overload/ER stress/autophagy axis in TCEP-induced cardiotoxicity.
JOURNAL OF INORGANIC BIOCHEMISTRY
(2022)
Article
Engineering, Environmental
Jing Zheng, Shane Antrobus, Wei Feng, Trevor N. Purdy, Bradley S. Moore, Isaac N. Pessah
Summary: This study found that bromopyrroles can influence neuronal network activity, with higher concentrations of TBP leading to a slow and sustained elevation in cytoplasmic calcium levels, ultimately resulting in loss of neuronal viability. The potential ecological and health impacts of bromopyrroles warrant further investigation.
ENVIRONMENTAL SCIENCE & TECHNOLOGY
(2021)
Article
Cell Biology
Toyokazu Kimura, Kazuki Kagami, Atsushi Sato, Ayumu Osaki, Kei Ito, Shunpei Horii, Takumi Toya, Nobuyuki Masaki, Risako Yasuda, Yuji Nagatomo, Takeshi Adachi
Summary: This study found that SERCA2 protein expression decreased in the aorta of diabetic mice, and CDN1163 improved aortic endothelial dysfunction, glucose tolerance, hepatosteatosis, and skeletal muscle function in these mice.
Article
Oncology
Zhidong Li, Jia Guo, Yunfei Bian, Mingsheng Zhang
Summary: The study found that IMD can protect cardiomyocytes against thapsigargin-induced apoptosis, at least partially by activating the protein kinase A/SERCA pathway.
MOLECULAR MEDICINE REPORTS
(2021)
Article
Biochemistry & Molecular Biology
Guido D. Petrovich, Gerardo R. Corradi, Hugo P. Adamo
Summary: This study elucidates the mechanism of Spf1p protein in protecting the endoplasmic reticulum and reveals the impact of different metal ions on its ATPase activity, especially the irreversible inactivation effect of Zn2+ and Cd2+.
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
(2022)
Article
Biochemistry & Molecular Biology
Weixing Zhu, Yanwei Duan, Jiqiang Chen, Hans Merzendorfer, Xu Zou, Qing Yang
Summary: The study identified a novel role of DmSERCA in chitin synthesis, demonstrating its physical interaction with epidermal chitin synthase and its importance in chitin deposition and structure formation in Drosophila melanogaster.
INSECT BIOCHEMISTRY AND MOLECULAR BIOLOGY
(2022)
Article
Pharmacology & Pharmacy
Iyuki Namekata, Ryosuke Odaka, Shunsuke Hamazaki, Hina Nisaka, Shogo Hamaguchi, Hikaru Tanaka
Summary: A method using fluorescence microscopy and specific inhibitors was developed to evaluate the activity of NCX and SERCA in mouse ventricular cardiomyocytes. Different adrenoceptor stimulations and inhibitors exhibited distinct effects on cytoplasmic Ca2+ concentration in non-beating ventricular cardiomyocytes, suggesting potential applications for pharmacological evaluations targeting NCX and SERCA.
BIOLOGICAL & PHARMACEUTICAL BULLETIN
(2021)
Article
Anatomy & Morphology
Wanying Chen, Mengmeng Li, Xiangyu Lei, Yawen Cheng, Xiaoyu Wu, Xinyue Sun, Yixuan Wu, Zhiheng Li, Guogang Luo, Meng Wei
Summary: Our study found that remote ischemic postconditioning (RIPostC) can alleviate brain ischemic injury by reducing endoplasmic reticulum (ER) stress, providing a theoretical basis for the protective mechanism of ischemic stroke.
MICROSCOPY RESEARCH AND TECHNIQUE
(2023)
Article
Cell Biology
Yuxia Zhang, Chigusa Kobayashi, Xiaohan Cai, Satoshi Watanabe, Akihisa Tsutsumi, Masahide Kikkawa, Yuji Sugita, Kenji Inaba
Summary: Using cryo-electron microscopy, we present structures of three intermediates of SERCA2b and reveal the transitions and processes involved in its catalytic cycle. These findings provide insights into how enzymes accelerate catalytic cycles.
Article
Fisheries
Junjie Yu, Wenrong Feng, Xue Chen, Changyou Song, Shengyan Su, Jiachun Ge, Yongkai Tang
Summary: This study cloned a cDNA encoding a putative SERCA protein from the Y-organs of E. sinensis. The Es-SERCA protein was widely expressed in various tissues, with the highest expression in the muscle. The study also revealed the functional role of SERCA in calcium homeostasis and its involvement in ecdysteroid synthesis during the moulting cycle.
AQUACULTURE RESEARCH
(2022)
Article
Cell Biology
Elisa Bovo, Roman Nikolaienko, Daniel Kahn, Ellen Cho, L. Seth Robia, V. Aleksey Zima
Summary: PS1 serves as an important regulator of cardiac Ca2+ pump function by interacting with SERCA2a, enhancing Ca2+ uptake at low ER Ca2+ loads and reducing uptake at high loads.
Article
Cardiac & Cardiovascular Systems
Jill K. Badin, Caleb Eggenberger, Stacey Dineen Rodenbeck, Zubair A. Hashmi, I-Wen Wang, Jose P. Garcia, Mouhamad Alloosh, Michael Sturek
Summary: In coronary smooth muscle of atherosclerotic coronary artery disease in metabolic syndrome swine, intracellular free Ca2+ dysregulation occurs. Increased [Ca2+](i) signaling in human CAD is associated with advanced age and a greater media area, while decreased signaling is related to a higher number of risk factors and plaque burden in human and swine CAD. Similar [Ca2+](i) dysregulation in human and Ossabaw swine CSM supports the translational relevance of this large animal model.
JOURNAL OF CARDIOVASCULAR TRANSLATIONAL RESEARCH
(2022)
Article
Medicine, Research & Experimental
Guanjie Li, Hiroyuki Suzuki, Tomokazu Ohishi, Teizo Asano, Tomohiro Tanaka, Miyuki Yanaka, Takuro Nakamura, Takeo Yoshikawa, Manabu Kawada, Mika K. K. Kaneko, Yukinari Kato
Summary: EpCAM is a type I transmembrane glycoprotein highly expressed on tumor cells, and it has been considered as a promising target for tumor diagnosis and therapy. In this study, a defucosylated version of an anti-EpCAM monoclonal antibody was generated and evaluated for its antitumor activity against EpCAM-positive cells. The results showed that the antibody exhibited potent cytotoxicity for EpCAM-overexpressing cells and suppressed tumor development in xenograft mouse models.
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
(2023)
Review
Biochemistry & Molecular Biology
Tomokazu Ohishi, Mika K. Kaneko, Yukihiro Yoshida, Atsuo Takashima, Yukinari Kato, Manabu Kawada
Summary: Colorectal cancer (CRC) is one of the most common and deadly types of cancer worldwide. Traditional treatment options for metastatic CRC (mCRC) were surgery or surgery combined with radiation and/or chemotherapy. However, the development of targeted drugs like cetuximab and bevacizumab has significantly improved patients' overall survival. This review discusses the latest molecular evidence and FDA-approved targeted drugs for mCRC, as well as their mechanisms of action and implications for treatment selection.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Hiroyuki Suzuki, Kaishi Kitamura, Nohara Goto, Kenichiro Ishikawa, Tsunenori Ouchida, Tomohiro Tanaka, Mika K. Kaneko, Yukinari Kato
Summary: CD44 promotes tumor progression by recruiting growth factors and acquiring stemness, invasiveness, and drug resistance. We have established various anti-CD44s and anti-CD44v monoclonal antibodies through immunization and in this study, we developed C(44)Mab-6, which could detect CD44v3 in various experiments and has potential applications in tumor diagnosis and therapy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Yuta Amagai, Momo Yamada, Toshiyuki Kowada, Tomomi Watanabe, Yuyin Du, Rong Liu, Satoshi Naramoto, Satoshi Watanabe, Junko Kyozuka, Tiziana Anelli, Tiziana Tempio, Roberto Sitia, Shin Mizukami, Kenji Inaba
Summary: Using super-resolution microscopy and Zn2+-probes targeted in specific Golgi subregions, this study reveals that Golgi-resident zinc transporters ZnT4, ZnT5/ZnT6, and ZnT7 regulate labile Zn2+ concentration at different regions of the Golgi, and their Zn2+ fluxes control the localization, trafficking, and client-retrieval activity of ERp44 along the early secretory pathway.
NATURE COMMUNICATIONS
(2023)
Article
Oncology
Tatsuya Deguchi, Naoya Maekawa, Satoru Konnai, Ryo Owaki, Kenji Hosoya, Keitaro Morishita, Motoji Nakamura, Tomohiro Okagawa, Hiroto Takeuchi, Sangho Kim, Ryohei Kinoshita, Yurika Tachibana, Madoka Yokokawa, Satoshi Takagi, Yukinari Kato, Yasuhiko Suzuki, Shiro Murata, Kazuhiko Ohashi
Summary: Immune checkpoint inhibitors (ICIs) show promise as a treatment option for canine cancers. However, the safety and efficacy of combining ICIs with radiation therapy have not been reported in dogs. A retrospective analysis of dogs with metastatic melanoma suggests that prior hypofractionated radiation therapy can enhance the response to anti-PD-L1 immunotherapy. Further studies are needed to confirm these findings.
Article
Immunology
Tomohiro Okagawa, Satoru Konnai, Hayato Nakamura, Otgontuya Ganbaatar, Yamato Sajiki, Kei Watari, Haruka Noda, Mitsuru Honma, Yukinari Kato, Yasuhiko Suzuki, Naoya Maekawa, Shiro Murata, Kazuhiko Ohashi
Summary: Blocking the interaction between PD-1 and PD-L1 can enhance T-cell responses induced by vaccination in cattle, suggesting the potential utility of anti-PD-L1 Ab in improving vaccination efficacy.
Article
Immunology
Nohara Goto, Hiroyuki Suzuki, Tomohiro Tanaka, Kenichiro Ishikawa, Tsunenori Ouchida, Mika K. Kaneko, Yukinari Kato
Summary: In this study, a specific and sensitive monoclonal antibody (mAb) for mouse EGFR (mEGFR) was developed using the Cell-Based Immunization and Screening (CBIS) method. The established antibody, EMab-300, showed reactivity with mEGFR-overexpressed cell lines using flow cytometry. The results suggest that EMab-300 can be used for the detection of mEGFR and may have potential applications in preclinical studies.
Article
Immunology
Yuma Kudo, Hiroyuki Suzuki, Tomohiro Tanaka, Mika K. Kaneko, Yukinari Kato
Summary: Pancreatic cancer has a poor prognosis due to the lack of early diagnostic biomarkers and resistance to chemotherapy. CD44 is a cancer stem cell marker and plays various roles in tumor promotion and drug resistance. This study successfully established a specific monoclonal antibody for CD44v5, which has potential applications in the diagnosis and therapy of pancreatic cancer.
Article
Oncology
Nohara Goto, Hiroyuki Suzuki, Ling Zheng, Yasuhito Okano, Yukari Okita, Yukihide Watanabe, Yukinari Kato, Mitsuyasu Kato
Summary: This study revealed that THG-1, a protein stimulated by transforming growth factor-beta 1 (TGF-β1), plays a crucial role in the proliferation, invasiveness, and tumor formation of squamous cell carcinomas (SCCs). THG-1 is phosphorylated by the receptor tyrosine kinase (RTK)-RAS- ERK pathway, which promotes oncogene-mediated tumorigenesis, and is involved in the alternative splicing of CD44 variants that regulate invasiveness, stemness, and oxidative stress resistance. The detection of THG-1 phosphorylation could be used for cancer diagnosis and therapy.
Article
Biochemical Research Methods
Yuriko Adachi, Mika K. Kaneko, Yukinari Kato, Terukazu Nogi
Summary: This study explores a method to prepare recombinant Fabs as secreted fusion proteins using a human growth hormone domain and an octa-histidine tag. The tagged Fabs can be purified using standard immobilized metal chelate affinity chromatography. The method allows for efficient production of diverse Fabs and the complete removal of tags while maintaining the native fold and binding affinity of the Fab.
PROTEIN EXPRESSION AND PURIFICATION
(2023)
Article
Immunology
Wisa Tiyamanee, Satoru Konnai, Tomohiro Okagawa, Yutaro Nojima, Otgontuya Ganbaatar, Naoya Maekawa, Rie Hasebe, Yumiko Kagawa, Yukinari Kato, Yasuhiko Suzuki, Shiro Murata, Kazuhiko Ohashi
Summary: Sheep have been utilized as a large animal model for studying infectious diseases, but the lack of staining antibodies and reagents has hindered the progress of immunological studies on sheep. Previous research showed that the PD-1/PD-L1 pathway plays a role in T-cell exhaustion and disease progression in bovine chronic infections, and blocking PD-1 and PD-L1 can restore T-cell functions in cattle. However, the immunological role of the PD-1/PD-L1 pathway in chronic diseases of sheep remains unknown.
VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY
(2023)
Article
Microbiology
Kotaro Ishida, Hirokazu Yagi, Yukinari Kato, Eiji Morita
Summary: This study investigates the role of N-glycosylation of flaviviral structural proteins in viral particle formation and secretion and finds that the amount of glycosylation regulates the release of subviral particles. Glycosylation mainly affects pre-Golgi transport.
Article
Oncology
Hiroyuki Suzuki, Tomokazu Ohishi, Mika K. Kaneko, Yukinari Kato
Summary: Podoplanin (PDPN) is a transmembrane sialo-glycoprotein that plays important roles in cancer progression and metastasis. A humanized and defucosylated monoclonal antibody (mAb) against PDPN (humLpMab-23-f) has been developed and shown to have antitumor activity in xenograft models of human tumor cells.
Article
Biochemistry & Molecular Biology
Kenichiro Ishikawa, Hiroyuki Suzuki, Mika K. Kaneko, Yukinari Kato
Summary: This article investigates the expression of CD44 in head and neck squamous cell carcinoma (HNSCC) and identifies a monoclonal antibody (C(44)Mab-18) that can recognize CD44, which has great potential for cancer diagnosis and therapy.
CURRENT ISSUES IN MOLECULAR BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Mayuki Tawara, Hiroyuki Suzuki, Nohara Goto, Tomohiro Tanaka, Mika K. K. Kaneko, Yukinari Kato
Summary: Researchers developed a monoclonal antibody, C(44)Mab-1, which can sensitively and specifically detect the expression of CD44v9 in cancer. This antibody is useful for flow cytometry, western blotting, and immunohistochemistry to detect CD44v9 in colorectal cancer.
CURRENT ISSUES IN MOLECULAR BIOLOGY
(2023)