Article
Chemistry, Multidisciplinary
Zijun Wu, Vinayak S. Khodade, Jean-Philippe R. Chauvin, Deborah Rodriguez, John P. Toscano, Derek A. Pratt
Summary: Hydropersulfides (RSSH) play important roles in vivo as scavengers of oxidants and electrophiles. They are highly reactive towards phospholipid-derived peroxyl radicals and can effectively inhibit ferroptosis. The reactivity of RSSH can be improved by designing specific precursors. RSSH and their precursors have been shown to inhibit ferroptosis in cell culture.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Review
Cell Biology
Pranavi Koppula, Li Zhuang, Boyi Gan
Summary: The overexpression of SLC7A11 promotes tumor growth while causing significant metabolic reprogramming costs for cancer cells. Cancer cells with high expression of SLC7A11 exhibit glucose- and glutamine-dependency, presenting potential metabolic vulnerabilities for therapeutic targeting.
Article
Biochemistry & Molecular Biology
Haruna Takeda, Shohei Murakami, Zun Liu, Tomohiro Sawa, Masatomo Takahashi, Yoshihiro Izumi, Takeshi Bamba, Hideyo Sato, Takaaki Akaike, Hiroki Sekine, Hozumi Motohashi
Summary: The excessive inflammatory response of macrophages is regulated by the metabolic alteration involving cysteine and its related metabolites. Activation of the cystine transporter xCT increases cysteine uptake by macrophages and contributes to the production of supersulfides, creating a negative feedback loop to limit excessive inflammation. Understanding the finely tuned regulation of macrophage inflammatory response by sulfur metabolism is important for disease pathogenesis and potential therapeutic strategies.
Article
Biochemistry & Molecular Biology
Sho Kobayashi, Takujiro Homma, Nobuaki Okumura, Jia Han, Keita Nagaoka, Hideyo Sato, Hiroyuki Konno, Sohsuke Yamada, Toshifumi Takao, Junichi Fujii
Summary: This study found that elevated levels of CNDP2 in xCT KO macrophages play a role in cell survival by increasing hydrolytic activity towards cysteinylglycine. Additionally, CNDP2 is essential for maintaining dipeptidase activity in the liver, kidney, and brain, and CNDP2 KO mice exhibited exacerbated liver and kidney damage when exposed to acetaminophen overdose. This suggests that CNDP2, through its role in redox balance, is particularly important for cells exposed to oxidative stress.
FREE RADICAL BIOLOGY AND MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Bindu D. Paul, Juan I. Sbodio, Solomon H. Snyder
Summary: This study found that cysteine metabolism is compromised at both transcriptional and post-translational levels in Huntington's disease, indicating that restoring cysteine homeostasis may be beneficial in treating this neurodegenerative disorder.
Article
Toxicology
Wendy L. Gonzalez-Alfonso, Petrosyan Pavel, Hernandez-Mercado Karina, Luz M. Del Razo, Luz C. Sanchez-Pena, Angelica Zepeda, Maria E. Gonsebatt
Summary: Exposure to toxic elements in drinking water, such as arsenic (As) and fluoride (F), can lead to memory and learning deficits in children. Rodent studies have shown that these neurotoxic effects are due to disruption of redox balance and synaptic transmission. Chronic exposure to As and F in drinking water resulted in reduced GSH levels, altered gene expression, and memory impairment in mice.
ARCHIVES OF TOXICOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Eric M. Brown, James P. Grace, Nimesh P. R. Ranasinghe Arachchige, Ned B. Bowden
Summary: Hydrogen sulfide is an important gasotransmitter in humans and plants, and exogenous hydrogen sulfide has many beneficial effects. However, tracking the location of exogenous hydrogen sulfide is a challenge. In this article, three key chemicals that release radiolabeled S-35 as hydrogen sulfide were synthesized. The radioactivity of the final products can be varied to meet different requirements.
Article
Biochemistry & Molecular Biology
Md Morshedul Alam, Akihiro Kishino, Eunkyu Sung, Hiroki Sekine, Takaaki Abe, Shohei Murakami, Takaaki Akaike, Hozumi Motohashi
Summary: NRF2 increases intracellular persulfides levels by upregulating the expression of cystine transporter xCT, thereby enhancing mitochondrial function.
Article
Chemistry, Multidisciplinary
Eric M. Brown, Ned B. Bowden
Summary: Trisulfides and higher polysulfides serve as important reservoirs of sulfane sulfur in the body and rapidly release persulfides, which have powerful antioxidant and gasotransmitter properties. However, their stabilities in aqueous systems and under different conditions remain poorly understood. This study synthesized biologically important trisulfides and a representative polysulfide and investigated their reactivity in buffered D2O. Results showed that tri- and tetrasulfides degrade rapidly in the presence of amines and are unstable under basic conditions. These findings have implications for understanding the role and stability of polysulfides in biological systems.
Review
Biochemistry & Molecular Biology
Xiaoguang Liu, Yilei Zhang, Li Zhuang, Kellen Olszewski, Boyi Gan
Summary: SLC7A11, a key player in cellular redox regulation, induces redox imbalance and subsequent cell death in cancer cells with high expression under glucose deprivation, highlighting potential therapeutic targets for SLC7A11(high) cancers.
Article
Biochemistry & Molecular Biology
Kang Wang, Zhengyang Zhang, Hsiang-i Tsai, Yanfang Liu, Jie Gao, Ming Wang, Lian Song, Xiongfeng Cao, Zhanxue Xu, Hongbo Chen, Aihua Gong, Dongqing Wang, Fang Cheng, Haitao Zhu
Summary: Ferroptosis, a form of iron-dependent cell death, has been implicated as a potential target for cancer therapy. The identification of BCAT2 as a regulator of ferroptosis suggests a novel therapeutic strategy for overcoming cancer resistance. Targeting BCAT2 may hold promise for enhancing the effectiveness of ferroptosis-inducing therapies in cancer treatment.
CELL DEATH AND DIFFERENTIATION
(2021)
Article
Biochemistry & Molecular Biology
Qamarul Hafiz Zainol Abidin, Tomoaki Ida, Masanobu Morita, Tetsuro Matsunaga, Akira Nishimura, Minkyung Jung, Naim Hassan, Tsuyoshi Takata, Isao Ishii, Warren Kruger, Rui Wang, Hozumi Motohashi, Masato Tsutsui, Takaaki Akaike
Summary: Reactive sulfur species, such as cysteine hydropersulfide and glutathione persulfide, are produced abundantly in both prokaryotes and eukaryotes, including mammals. Cysteinyl-tRNA synthetase (CARS) has been identified as a new cysteine persulfide synthase (CPERS) responsible for the production of most reactive persulfides. However, the contribution of other enzymes, such as 3-mercaptopyruvate sulfurtransferase (3-MST), cystathionine beta-synthase (CBS), and cystathionine gamma-lyase (CSE), to reactive persulfide production is still debated. In this study, the authors used sulfur metabolome analysis to demonstrate that 3-MST, CBS, and CSE are not major sources of reactive persulfides in mammals, and CARS/CPERS is the principal enzyme involved.
Review
Chemistry, Multidisciplinary
Ya-Lin Qi, Hai-Rong Wang, Li-Li Chen, Yong-Tao Duan, Sheng-Yu Yang, Hai-Liang Zhu
Summary: Ferroptosis is an iron-dependent, non-apoptotic form of programmed cell death involved in the development and progression of various diseases. Small-molecule fluorescent probes have been used to study ferroptosis by tracking biomolecules or microenvironment-related parameters in vitro and in vivo.
CHEMICAL SOCIETY REVIEWS
(2022)
Article
Chemistry, Multidisciplinary
Vinayak S. Khodade, Sahil C. Aggarwal, Blaze M. Pharoah, Nazareno Paolocci, John P. Toscano
Summary: The discovery of alkylsulfenyl thiocarbonates as a new class of RSSH precursors has significant implications in biological systems, with the ability to release RSSH under physiologically relevant conditions and protect cells against oxidative stress. The release kinetics of RSSH from these precursors can be tuned through electronic modification, demonstrating the potential for increasing intracellular RSSH levels.
Article
Microbiology
Touya Toyomoto, Katsuhiko Ono, Tomoo Shiba, Kenta Momitani, Tianli Zhang, Hiroyasu Tsutsuki, Takeshi Ishikawa, Kanae Hoso, Koma Hamada, Azizur Rahman, Liping Wen, Yosuke Maeda, Keiichi Yamamoto, Masao Matsuoka, Kenjiro Hanaoka, Takuro Niidome, Takaaki Akaike, Tomohiro Sawa
Summary: Blocking metabolic pathways essential for bacterial growth while not affecting mammalian cells is a key concept in developing selective antibacterial agents. This study demonstrates that alkyl gallates can act as potent inhibitors of CysE, reducing l-cysteine synthesis in bacteria and enhancing the susceptibility of drug-resistant Gram-negative bacteria to antibiotics.
FRONTIERS IN MICROBIOLOGY
(2023)
Article
Nutrition & Dietetics
Takamasa Mizota, Takako Hishiki, Masahiro Shinoda, Yoshiko Naito, Kazuya Hirukawa, Yohei Masugi, Osamu Itano, Hideaki Obara, Minoru Kitago, Hiroshi Yagi, Yuta Abe, Kentaro Matsubara, Makoto Suematsu, Yuko Kitagawa
Summary: This study found that in acute liver failure, there is a decrease in metabolites related to glycolysis and pentose phosphate pathways, as well as high-energy phosphornucleotides, while methionine and its metabolites are increased. Furthermore, the increase in hypotaurine and taurine coincides with a decrease in total glutathione, suggesting a potential role of the hypotaurine-taurine pathway in oxidative stress protection.
JOURNAL OF CLINICAL BIOCHEMISTRY AND NUTRITION
(2022)
Article
Biology
Motoyoshi Kimura, Akiko Saito, Shoko Onodera, Takashi Nakamura, Makoto Suematsu, Seikou Shintani, Toshifumi Azuma
Summary: The simultaneous stimulation of primary cultured mesenchymal cells with CHIR99021 and FGF8 significantly upregulates odonto/osteoblast proteins in mouse tooth germs, indicating the essential role of coordinated action of canonical Wnt/beta-catenin and FGF8 signals in odontoblast differentiation.
MEDICAL MOLECULAR MORPHOLOGY
(2022)
Article
Neurosciences
Yoshiteru Shimoda, Kaoru Beppu, Yoko Ikoma, Yosuke M. Morizawa, Satoshi Zuguchi, Utaro Hino, Ryutaro Yano, Yuki Sugiura, Satoru Moritoh, Yugo Fukazawa, Makoto Suematsu, Hajime Mushiake, Nobukazu Nakasato, Masaki Iwasaki, Kenji F. Tanaka, Teiji Tominaga, Ko Matsui
Summary: This study found that optogenetic neuronal stimulation can induce hyperexcitability in the rat brain, but continued stimulation can lead to a state resistant to seizures induction. Moderate astrocyte activation was associated with the acquisition of resilience in the brain.
NEUROBIOLOGY OF DISEASE
(2022)
Article
Multidisciplinary Sciences
Kodai Abe, Yasuaki Kabe, Susumu Uchiyama, Yuka W. Iwasaki, Hirotsugu Ishizu, Yoshifumi Uwamino, Toshiki Takenouchi, Shunsuke Uno, Makoto Ishii, Takahiro Maruno, Masanori Noda, Mitsuru Murata, Naoki Hasegawa, Hideyuki Saya, Yuko Kitagawa, Koichi Fukunaga, Masayuki Amagai, Haruhiko Siomi, Makoto Suematsu, Kenjiro Kosaki
Summary: Recent clinical trial showed 3CL(pro) inhibitor significantly reduces risk of hospitalization/death, while SARS-CoV-2 sub-lineage with reduced 3CL(pro) enzymatic activity exhibits milder clinical course. Structural perturbation surrounding substrate-binding region of mutant 3CL(pro) may explain the decreased activity.
SCIENTIFIC REPORTS
(2022)
Article
Biochemistry & Molecular Biology
Takaaki Tatsuguchi, Takehito Uruno, Yuki Sugiura, Kounosuke Oisaki, Daisuke Takaya, Daiji Sakata, Yoshihiro Izumi, Takaya Togo, Yuko Hattori, Kazufumi Kunimura, Tetsuya Sakurai, Teruki Honma, Takeshi Bamba, Masafumi Nakamura, Motomu Kanai, Makoto Suematsu, Yoshinori Fukui
Summary: This study demonstrates that inhibiting SULT2B1b can enhance anti-tumor immunity by suppressing CS-mediated T cell exclusion. Administration of the inhibitor 3 beta-OH-5-Chln can reduce CS levels in tumors and increase infiltration of CD8(+) T cells, leading to the suppression of CS-producing tumor growth.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Immunology
Tomoko Matsubara, Takahito Iga, Yuki Sugiura, Dai Kusumoto, Tsukasa Sanosaka, Ikue Tai-Nagara, Norihiko Takeda, Guo-Hua Fong, Kosei Ito, Masatsugu Ema, Hideyuki Okano, Jun Kohyama, Makoto Suematsu, Yoshiaki Kubota
Summary: Using imaging techniques and single-cell RNA sequencing, researchers identified a unique endothelial subtype, periodontal tip-like endothelial cells, responsible for dentinogenesis. These capillaries facilitate dentin formation by transporting phosphate and interacting with odontoblasts. The angiogenic-odontogenic coupling represents a fundamental cell-to-cell communication mechanism in tooth formation.
JOURNAL OF EXPERIMENTAL MEDICINE
(2022)
Article
Biology
Sayaka Ueno, Tamotsu Sudo, Hideyuki Saya, Eiji Sugihara
Summary: This study reveals that pigment epithelium-derived factor (PEDF) promotes the dissemination of ovarian cancer by inducing IL-10 expression in macrophages. High PEDF gene expression is associated with poor prognosis in ovarian cancer patients, and elevated PEDF levels are correlated with early recurrence. BET inhibitors reduce PEDF expression and limit both cancer cell survival and macrophage induction.
COMMUNICATIONS BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Haruki Inoue, Eriko Aimono, Akiyoshi Kasuga, Haruto Tanaka, Aika Iwasaki, Hideyuki Saya, Yoshimi Arima
Summary: Our mouse BTC models are suitable for studying BTC carcinogenesis and may contribute to the development of new therapeutic strategies. Analysis of images of mouse and human tumor tissues reveals similarities in tissue structure between the two, suggesting similarities in tumor characteristics independent of animal species. Additionally, our pixel-level clustering model can serve as a new diagnostic tool for BTC.
Article
Endocrinology & Metabolism
Takashi Nakamura, Sayako Honda, Shinichirou Ito, Toshihide Mizoguchi, Takehiro Yamamoto, Masataka Kasahara, Yasuaki Kabe, Koichi Matsuo, Makoto Suematsu
Summary: In this study, a new differentiated osteoblast- and osteocyte-specific Cre knock-in mouse model was created, and the efficient expression of both Dmp1 and Cre proteins was confirmed using the 2A self-cleaving peptide. This model is a useful tool for studying the functioning of various genes in hard tissues.
JOURNAL OF BONE AND MINERAL METABOLISM
(2023)
Article
Medicine, Research & Experimental
Tomofumi Ando, Ikue Tai-Nagara, Yuki Sugiura, Dai Kusumoto, Koji Okabayashi, Yasuaki Kido, Kohji Sato, Hideyuki Saya, Sutip Navankasattusas, Dean Y. Li, Makoto Suematsu, Yuko Kitagawa, Elena Seiradake, Satoru Yamagishi, Yoshiaki Kubota
Summary: Blood vessel abnormalities in cancer can be targeted therapeutically to suppress cancer progression, according to a study. Researchers found that a molecule called fibronectin leucine-rich transmembrane protein 2 (FLRT2) is expressed in abnormal blood vessels of advanced colorectal cancers in humans. Deleting FLRT2 in endothelial cells selectively pruned abnormal blood vessels and suppressed tumor metastasis. Additionally, FLRT2 deletion increased the number of mature vessels, enhancing the antitumor effects of immune checkpoint blockers. The study suggests that targeting tumor-specific interendothelial adhesions could be a safe and effective therapeutic option.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Article
Immunology
Takaaki Tatsuguchi, Takehito Uruno, Yuki Sugiura, Daiji Sakata, Yoshihiro Izumi, Tetsuya Sakurai, Yuko Hattori, Eiji Oki, Naoto Kubota, Koshiro Nishimoto, Masafumi Oyama, Kazufumi Kunimura, Takuto Ohki, Takeshi Bamba, Hideaki Tahara, Michiie Sakamoto, Masafumi Nakamura, Makoto Suematsu, Yoshinori Fukui
Summary: Effective tumor immunotherapy requires physical contact between T cells and cancer cells. However, cancer cells can produce a cholesterol sulfate that inhibits DOCK2, preventing infiltration of effector T cells.
INTERNATIONAL IMMUNOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Nae Takizawa, Susumu Tanaka, Koshiro Nishimoto, Yuki Sugiura, Makoto Suematsu, Chisato Ohe, Haruyuki Ohsugi, Yosuke Mizuno, Kuniaki Mukai, Tsugio Seki, Kenji Oki, Celso E. Gomez-Sanchez, Tadashi Matsuda
Summary: This study presents an unusual case of familial hyperaldosteronism type 3 (FH3) in a young woman who was first diagnosed with primary aldosteronism at the age of 6 years. Despite undergoing unilateral adrenalectomy to alleviate hyperaldosteronism, the hyperaldosteronism persisted. At the age of 26 years, additional adrenal tumors were discovered and removed. Histological, immunohistochemical, and molecular evaluation of the tumors and adrenal gland showed the presence of aldosterone synthase (CYP11B2) immunoreactivity, as well as a somatic beta-catenin activating mutation in the larger tumor. In situ visualization of aldosterone also revealed its presence only in the subcapsular regions of the adrenal gland and not in the tumors.
CURRENT ISSUES IN MOLECULAR BIOLOGY
(2022)
Article
Cell Biology
Lena Sasaki, Yuki Hamada, Daisuke Yarimizu, Tomo Suzuki, Hiroki Nakamura, Aya Shimada, Khanh Tien Nguyen Pham, Xinyan Shao, Koki Yamamura, Tsutomu Inatomi, Hironobu Morinaga, Emi K. Nishimura, Fujimi Kudo, Ichiro Manabe, Shogo Haraguchi, Yuki Sugiura, Makoto Suematsu, Shigeru Kinoshita, Mamiko Machida, Takeshi Nakajima, Hiroshi Kiyonari, Hitoshi Okamura, Yoshiaki Yamaguchi, Takahito Miyake, Masao Doi
Summary: Meibomian gland dysfunction and dry eye disease associated with aging can be ameliorated by the reactivation of local intracrine activity through 3β-HSD enzyme, which can be achieved by boosting the availability of its coenzyme NAD(+). This study highlights the importance of local steroidogenesis in combating age-related meibomian gland dysfunction.
