Article
Immunology
Nikhil Ponnoor Anto, Amitha Muraleedharan, Pulak Ranjan Nath, Zuoming Sun, Chen Keasar, Etta Livneh, Alex Braiman, Amnon Altman, Kok-Fai Kong, Noah Isakov
Summary: Protein kinase C-α (PKC-α) is selectively expressed in T lymphocytes and plays a crucial role in T cell activation and proliferation. The phosphorylation of Thr(335)-Pro residue in the regulatory domain of PKC-α is important for its activation and localization at the immunological synapse. The peptidyl-prolyl cis-trans isomerase Pin1 interacts with PKC-α through the phosphorylated Thr(335)-Pro motif, and this interaction is involved in early activation events in TCR-triggered T cells.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Weibei Sheng, Qichang Wang, Haotian Qin, Siyang Cao, Yihao Wei, Jian Weng, Fei Yu, Hui Zeng
Summary: Osteoarthritis (OA) is a common degenerative joint disease that is exacerbated by population aging, resulting in a significant economic burden. Current therapies are inadequate, but research on peroxisome proliferator-activated receptors (PPARs) shows promise in slowing OA progression. PPARs have emerged as potential targets for effective OA treatments.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Yanhao Qiu, Mailin Gan, Xingyu Wang, Tianci Liao, Qiuyang Chen, Yuhang Lei, Lei Chen, Jinyong Wang, Ye Zhao, Lili Niu, Yan Wang, Shunhua Zhang, Li Zhu, Linyuan Shen
Summary: Excessive expansion of adipocytes can lead to ectopic fat deposition, increasing the risk of metabolic diseases. Peroxisome proliferator-activated receptor gamma (PPARγ) plays a crucial role in fat cell differentiation and adipogenesis.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Article
Microbiology
Yi-Hsin Lai, Tai-Chieh Wu, Bo-Yang Tsai, Yuan-Pin Hung, Hsiao-Ju Lin, Yau-Sheng Tsai, Wen-Chien Ko, Pei-Jane Tsai
Summary: PPAR-γ plays an important role in the pathogenesis of CDI by regulating colonic inflammation and integrity.
FRONTIERS IN MICROBIOLOGY
(2022)
Article
Cardiac & Cardiovascular Systems
Shi Fang, M. Christine Livergood, Pablo Nakagawa, Jing Wu, Curt D. Sigmund
Summary: This review focuses on the mechanisms by which nuclear receptors mediate transcriptional responses, with a specific emphasis on the role of PPARγ in regulating blood pressure. Genetic and clinical trial data demonstrate the importance of PPARγ in hypertension, and the tissue- and cell-specific molecular mechanisms by which PPARs modulate blood pressure and related phenotypes are detailed. The role of placental PPARs in preeclampsia is also discussed, along with future research directions and implications for novel therapies.
CIRCULATION RESEARCH
(2021)
Article
Engineering, Environmental
Clementine Garoche, Abdelhay Boulahtouf, Marina Grimaldi, Barbara Chiavarina, Lucia Toporova, Marjo J. den Broeder, Juliette Legler, William Bourguet, Patrick Balaguer
Summary: This study demonstrated the interspecies differences in PPAR gamma activities among human, mouse, zebrafish, and xenopus, highlighting the importance of using species-specific models to study endocrine and metabolism disruption by environmental chemicals.
ENVIRONMENTAL SCIENCE & TECHNOLOGY
(2021)
Article
Pathology
Shinji Kaba, Yoshitaka Kawai, Yuki Tanigami, Hiroe Ohnishi, Tomoko Kita, Masayoshi Yoshimatsu, Koichi Omori, Yo Kishimoto
Summary: This study aimed to evaluate the effects of pioglitazone on macrophage phenotype and fibrosis following vocal fold injury. The results showed that pioglitazone reduced the expression of Ccl2, inhibited the accumulation of inflammatory macrophages, and improved tissue repair in a PPARy-dependent manner, resulting in decreased fibrosis.
AMERICAN JOURNAL OF PATHOLOGY
(2022)
Article
Plant Sciences
Haoyang Zou, Yiyao Gong, Haiqing Ye, Cuiping Yuan, Tiezhu Li, Jie Zhang, Li Ren
Summary: This study summarizes the physiological importance and clinical significance of PPARs and reviews the experimental evidence that natural products mediate metabolic syndrome via PPARs. The majority of currently described natural compounds are mild PPAR-selective agonists with therapeutic effects that are equivalent to synthetic medicines but less harmful adverse effects. Conclusion: PPAR agonists can be combined with natural products to treat and prevent metabolic syndrome.
Article
Biochemistry & Molecular Biology
Zhen Wang, Shu Yang, Yan Li, Yongying Zhou, Daoquan Liu, Jianmin Liu, Michael E. DiSanto, Xinhua Zhang
Summary: BPH is a common disease in elderly men and is closely related to MetS. This study demonstrates that SV can modulate cell proliferation, apoptosis, tissue fibrosis, and the EMT process in the prostate through crosstalk between PPAR gamma and WNT/beta-catenin pathways.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Cell Biology
Iason Psilopatis, Kleio Vrettou, Florian Nima Fleckenstein, Stamatios Theocharis
Summary: Preeclampsia is a common hypertensive disorder in pregnancy, and PPARs play a significant role in its pathophysiology. Studies have shown contradictory conclusions regarding PPAR expression in preeclamptic placentae, but PPAR gamma agonists have been identified as a novel and potent anti-preeclamptic treatment option.
Article
Agriculture, Dairy & Animal Science
Guoyan Wang, Jun Zhang, Shengru Wu, Senlin Qin, Yining Zheng, Chao Xia, Huijun Geng, Junhu Yao, Lu Deng
Summary: Cattle have a unique mechanism for efficient hepatic gluconeogenesis, involving the high expression of specific genes and the activation of the mTORC1 signaling pathway. These findings are important for understanding the mechanism underlying the quantitative differences in hepatic gluconeogenesis efficiency between cattle and non-ruminant animals.
Article
Chemistry, Physical
Abhigyan Sengupta, Lorenz E. Rognoni, Ulrich Merkel, Gabriel Zoldak, Matthias Rief
Summary: Prolyl isomerization catalyzed by the PPIase enzyme plays a crucial role in cellular signaling and molecular timing. This study demonstrates a 25-fold acceleration of trans-cis isomerization rate and a stabilization effect on the cis-isomer by SlyD in a single-molecule experiment with FlnA20 protein.
JOURNAL OF PHYSICAL CHEMISTRY B
(2021)
Review
Biochemistry & Molecular Biology
Iason Psilopatis, Kleio Vrettou, Constantinos Troungos, Stamatios Theocharis
Summary: Endometrial carcinoma is the most common malignant tumor of the female genital tract in the United States. Peroxisome proliferator-activated receptors (PPARs) are nuclear receptor proteins which regulate gene expression. In our literature review of 27 relevant studies published between 2000 and 2023, it was found that PPAR alpha and PPAR beta/delta isoforms were upregulated in endometrial cancer cells, while PPAR gamma levels were significantly lower. Interestingly, PPAR agonists were found to be potent anti-cancer therapeutic alternatives. Overall, PPARs seem to play a significant role in endometrial cancer.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Oncology
Nasim Dana, Gordon A. Ferns, Reza Nedaeinia, Shaghayegh Haghjooy Javanmard
Summary: Obesity affects tumor development and interacts with leptin and peroxisome proliferator-activated receptors. Studies have shown an association between obesity and various types of cancer, including breast cancer.
CLINICAL & TRANSLATIONAL ONCOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Soma Saeidi, Su-Jung Kim, Yanymee N. Guillen-Quispe, Achanta Sri Venkata Jagadeesh, Hyeong-Jun Han, Seung Hyeon Kim, Xiancai Zhong, Juan-Yu Piao, Seong-Jin Kim, Joon Jeong, Yun Jin Shin, Yoon Jin Cha, Han-Byoel Lee, Wonshik Han, Sang-Hyun Min, Wang Tian, Hiroshi Kitamura, Young-Joon Surh
Summary: Pin1 is frequently overexpressed in various types of malignancy, including triple-negative breast cancer, and plays a role in stabilizing and activating Nrf2 by competing with Keap1 for Nrf2 binding, thus promoting breast cancer progression. Through its interaction with phosphorylated Nrf2 and Keap1 residues, Pin1 alters the stability and function of Nrf2, leading to the accumulation of Nrf2 in the nucleus and contributing to breast cancer development and progression.
Review
Biochemistry & Molecular Biology
Hironari Nishizawa, Mie Yamanaka, Kazuhiko Igarashi
Summary: Ferroptosis is a form of cell death triggered by intracellular peroxidation of cell membrane phospholipids. It is regulated by transcription factors NRF2 and BACH1, which control various pathways and processes involved in ferroptosis.
Article
Biochemistry & Molecular Biology
Kei Segawa, Kazuhiko Igarashi, Kazutaka Murayama
Summary: The function of the transcription factor BACH1 is regulated by heme binding to multiple Cys-Pro (CP) motifs within its intrinsically disordered regions. The individual CP motifs contribute to the regulation of BACH1 activity by accepting heme in different coordination manners and their spatial locations are important for their individual functions. The presence of multiple CP motifs with distinct roles ensures the multifaceted, strict regulation of BACH1 by heme.
Article
Biochemistry & Molecular Biology
Kyota Yasuda, Tomonobu M. Watanabe, Myeong-Gyun Kang, Jeong Kon Seo, Hyun-Woo Rhee, Shin-ichi Tate
Summary: The presence of valosin-containing protein (VCP) in FUS granules plays a role in regulating their stability, with VCP consuming ATP to reduce ATP concentrations in the granules. Initial colocalization of VCP stabilizes the granules, while prolonged colocalization destabilizes the granules.
Article
Biochemistry & Molecular Biology
Mahabub Alam, Hiroki Shima, Yoshitaka Matsuo, Nguyen Chi Long, Mitsuyo Matsumoto, Yusho Ishii, Nichika Sato, Takato Sugiyama, Risa Nobuta, Satoshi Hashimoto, Liang Liu, Mika K. Kaneko, Yukinari Kato, Toshifumi Inada, Kazuhiko Igarashi
Summary: The study reveals the regulatory role of methionine adenosyltransferase (MAT) and S-adenosylmethionine (SAM) in protein synthesis. MAT2A, present in cancer cells, is positively correlated with cell proliferation. The experiment shows that under normal culture conditions, MAT2A limits protein synthesis. Additionally, MAT2 interacts with proteins involved in rRNA processing and ribosome biogenesis, and its inhibition results in reduced processing of 18S rRNA. The study also demonstrates the dynamic methylation of translation factors in response to MAT2A activity.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Koya Ono, Tohru Fujiwara, Kei Saito, Hironari Nishizawa, Noriyuki Takahashi, Chie Suzuki, Tetsuro Ochi, Hiroki Kato, Yusho Ishii, Koichi Onodera, Satoshi Ichikawa, Noriko Fukuhara, Yasushi Onishi, Hisayuki Yokoyama, Rie Yamada, Yukio Nakamura, Kazuhiko Igarashi, Hideo Harigae
Summary: X-linked sideroblastic anemia (XLSA), the most common form of congenital sideroblastic anemia, is caused by a germline mutation in the erythroid-specific 5-aminolevulinate synthase (ALAS2) gene. XLSA clones derived from human umbilical cord blood exhibited increased ring sideroblast formation and impaired hemoglobin biosynthesis.
SCIENTIFIC REPORTS
(2022)
Article
Plant Sciences
Baifeng Zhou, Hiroki Shima, Kazuhiko Igarashi, Kan Tanaka, Sousuke Imamura
Summary: In this study, researchers identified a negative domain of CmMYB1, a transcription factor involved in nitrogen assimilation in plants. They found that this negative domain, along with a protein called CmNDB1, regulates the function of CmMYB1 under nitrogen-repleted conditions. These findings provide important insights into the regulatory mechanisms of nitrogen assimilation in C. merolae.
FRONTIERS IN PLANT SCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Pooja Pradhan, Vijith Vijayan, Karsten Cirksena, Falk F. R. Buettner, Kazuhiko Igarashi, Roberto Motterlini, Roberta Foresti, Stephan Immenschuh
Summary: In this study, the role of BACH1 in mouse macrophages was investigated using a proteomics approach. The results showed that genetic deletion of BACH1 led to reduced levels of mitochondrial proteins, altered mitochondrial energy metabolism, and increased activation of the NLRP3 inflammasome. This study highlights the critical role of BACH1 in modulating macrophage immune responses.
Article
Biochemistry & Molecular Biology
Takumi Kouketsu, Rina Monma, Yuri Miyairi, Shun Sawatsubashi, Hiroki Shima, Kazuhiko Igarashi, Akira Sugawara, Atsushi Yokoyama
Summary: This study investigates the interaction between HNF4α and IRF2BP2 and their regulatory effects on gluconeogenic gene expression. The experiments reveal that IRF2BP2 functions as a novel co-repressor of HNF4α, suppressing its transcriptional activity through its E3 ubiquitin ligase activity. This finding uncovers a new characteristic of nuclear receptor co-regulators.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Lun Cai, Ali S. Arbab, Tae Jin Lee, Ashok Sharma, Bobby Thomas, Kazuhiko Igarashi, Raghavan Pillai Raju
Summary: The deletion of Bach1 gene improves organ function and survival in sepsis. It enhances antioxidant response, reduces oxidative stress and inflammation, preserves mitochondrial function, and regulates gene expression related to lipid metabolism. Bach1 deficiency also improves liver and lung blood flow in septic mice.
FREE RADICAL BIOLOGY AND MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Liang Liu, Mitsuyo Matsumoto, Miki Matsui-Watanabe, Kyoko Ochiai, Bert K. K. Callens, Long Chi Nguyen, Yushi Kozuki, Miho Tanaka, Hironari Nishizawa, Kazuhiko Igarashi
Summary: The TBK1-BACH1 pathway promotes cancer cell metastasis by increasing labile iron within cells.
Article
Hematology
Masatoshi Ikeda, Hiroki Kato, Hiroki Shima, Mitsuyo Matsumoto, Eijiro Furukawa, Yan Yan, Ruiqi Liao, Jian Xu, Akihiko Muto, Tohru Fujiwara, Hideo Harigae, Emery H. Bresnick, Kazuhiko Igarashi
Summary: Iron deficiency promotes mitochondrial retention in red blood cells, while heme promotes mitochondrial clearance and erythroblast differentiation. The transcription factor GATA1 regulates autophagy and induces mitophagy through a heme-dependent mechanism. This mechanism provides a molecular framework for understanding this important cell biological process.
EXPERIMENTAL HEMATOLOGY
(2023)
Article
Hematology
Koki Nagai, Tetsuya Niihori, Akihiko Muto, Yoshikazu Hayashi, Taiki Abe, Kazuhiko Igarashi, Yoko Aoki
Summary: Radioulnar synostosis with amegakaryocytic thrombocytopenia (RUSAT) is an inherited bone marrow failure syndrome caused by missense mutations in the MECOM gene. Knockin mice harboring RUSAT-associated MECOM mutations recapitulate the bone marrow dysfunction observed in RUSAT patients.
Review
Immunology
Kyoko Ochiai, Kazuhiko Igarashi
Summary: BACH2 is a transcriptional repressor that regulates gene expression in B cells, promoting antibody class switch and affinity maturation while repressing plasma-cell differentiation. Recent studies suggest that BACH2 may have diverse functions, including gene activation. Understanding these new functions could provide insights into preventing human immune deficiencies.
INTERNATIONAL IMMUNOLOGY
(2023)
Meeting Abstract
Hematology
Koya Ono, Tohru Fujiwara, Hiroki Shima, Hironari Nishizawa, Chie Suzuki, Noriyuki Takahashi, Hiroki Kato, Koichi Onodera, Satoshi Ichikawa, Noriko Fukuhara, Yasushi Onishi, Hisayuki Yokoyama, Yukio Nakamura, Kazuhiko Igarashi, Hideo Harigae
Meeting Abstract
Oncology
Kazuhiko Igarashi, Hironari Nishizawa, Mitsuyo Matsumoto
