Article
Medicine, Research & Experimental
Tianxiao Wang, Yongjun Zhu, Lu Chen, Wenxin Zhang, Huijie Qi, Xiaojin Shi, Mingkang Zhong, Haifei Chen, Qunyi Li
Summary: This study investigated the role of estrogen-related receptor gamma (ESRRG) in metabolic reprogramming in esophageal squamous cell carcinoma (ESCC). The results showed that ESRRG inhibited the growth, tumorigenesis, and glycolysis activity of ESCC cells by downregulating the expression of Pyruvate kinase M2 (PKM2). In addition, the ESRRG-specific agonist, DY131, suppressed ESCC cell proliferation and glycolysis activity by modulating genes in the glycolysis pathway, and enhanced immune checkpoint inhibition.
JOURNAL OF TRANSLATIONAL MEDICINE
(2023)
Article
Medicine, Research & Experimental
Dingbang Xie, Yunteng Xu, Yimin Zhang, Wanping Cai, Xin Lan, Hui Yan
Summary: Postmenopausal osteoporosis (PMOP) is characterized by an imbalance between bone formation and bone resorption. In this study, it was found that icariin (ICA) could alleviate PMOP by inhibiting pyruvate dehydrogenase kinase 1 (PDK1) in osteoclasts, indicating its potential for clinical use.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Oncology
Caroline E. Nunes-Xavier, Janire Mingo, Maite Emaldi, Karine Flem-Karlsen, Gunhild M. Maelandsmo, Oystein Fodstad, Roberto Llarena, Jose I. Lopez, Rafael Pulido
Summary: This study revealed heterogeneous expression of PDH complex components in PCa tumors, with PDH complex components being related to AR signaling and PDK2 expression associated with poor PCa prognosis. These findings highlight the potential of targeting PDH complex components for intervention in PCa.
FRONTIERS IN ONCOLOGY
(2022)
Article
Cardiac & Cardiovascular Systems
Qinfeng Li, Chao Li, Abdallah Elnwasany, Gaurav Sharma, Yu A. An, Guangyu Zhang, Waleed M. Elhelaly, Jun Lin, Yingchao Gong, Guihao Chen, Meihui Wang, Shangang Zhao, Chongshan Dai, Charles D. Smart, Juan Liu, Xiang Luo, Yingfeng Deng, Lin Tan, Shuang-Jie Lv, Shawn M. Davidson, Jason W. Locasale, Philip L. Lorenzi, Craig R. Malloy, Thomas G. Gillette, Matthew G. Vander Heiden, Philipp E. Scherer, Luke I. Szweda, Guosheng Fu, Zhao V. Wang
Summary: PKM1 plays a crucial role in maintaining a homeostatic response in the heart under hemodynamic stress, protecting against cardiac dysfunction and fibrosis caused by pressure overload. Furthermore, PKM1 is essential for enhancing glycolytic flux, mitochondrial respiration, and ATP production under pressure overload at a mechanistic level.
Review
Biochemistry & Molecular Biology
Russel J. Reiter, Ramaswamy Sharma, Sergio Rosales-Corral
Summary: Glucose is a crucial nutrient for cells, but in some pathological cells, aerobic glycolysis may occur due to the inhibition of pyruvate dehydrogenase complex. Glycolytics like melatonin can convert diseased cells to a healthier phenotype by inhibiting hypoxia-inducible factor-1 alpha and promoting intramitochondrial conversion of pyruvate into acetyl coenzyme A, thus explaining its actions in inhibiting various diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biotechnology & Applied Microbiology
Tao Si, Xuejian Ning, Hongwei Zhao, Mingmin Zhang, Ping Huang, Zhengguo Hu, Liu Yang, Lizhu Lin
Summary: The study found that miR-9-5p promotes proliferation, invasion, and migration of HCC cells by regulating the expression of PDK4, enhancing mitochondrial activity and energy metabolism, while suppressing apoptosis, ultimately increasing tumorigenicity in mouse xenograft models. This suggests that miR-9-5p and PDK4 could be potential therapeutic targets for preventing recurrence and metastasis of HCC.
CANCER GENE THERAPY
(2021)
Article
Biochemistry & Molecular Biology
Nives Skorja Milic, Klemen Dolinar, Katarina Mis, Urska Matkovic, Marusa Bizjak, Mojca Pavlin, Matej Podbregar, Sergej Pirkmajer
Summary: Inhibition of pyruvate dehydrogenase kinase (PDK) by Dichloroacetate (DCA) can reduce the abundance of PDK isoenzymes in a cell-type-specific manner via both transcriptional and post-transcriptional mechanisms. The differential response of PDK isoenzymes to DCA in cancer cells and muscle cells highlights the importance of understanding the pharmacological effects of DCA in different cell types.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Nutrition & Dietetics
Song Hee Lee, Bo Young Choi, A. Ra Kho, Dae Ki Hong, Beom Seok Kang, Min Kyu Park, Si Hyun Lee, Hui Chul Choi, Hong Ki Song, Sang Won Suh
Summary: The combined treatment of pyruvate and DCA shows protective effects against seizure-induced hippocampal neuronal cell death by increasing the proportion of pyruvate converted to ATP.
Article
Biochemistry & Molecular Biology
Yudi Ma, Xiaohui Lai, Zhongling Wen, Ziling Zhou, Minkai Yang, Qingqing Chen, Xuan Wang, Feng Mei, Liu Yang, Tongming Yin, Shucun Sun, Guihua Lu, Jinliang Qi, Hongyan Lin, Hongwei Han, Yonghua Yang
Summary: The Warburg effect is essential for tumor proliferation, but reversing it can lead to a novel anti-cancer strategy. Two key enzymes in tumor glucose metabolism pathway, PKM2 and PDK1, not only contribute to the Warburg effect, but also serve as druggable targets for CRC. A series of benzenesulfonyl shikonin derivatives were designed to simultaneously regulate PKM2 and PDK1. Among them, compound Z10 acted as a PKM2 activator and PDK1 inhibitor, significantly inhibiting glycolysis and remodeling tumor metabolism. In addition, Z10 inhibited CRC cell proliferation and migration, and induced apoptosis. Furthermore, Z10 showed in vivo anti-tumor activity with lower toxicity compared to shikonin. Our findings suggest that altering tumor energy metabolism through multi-target synergies is feasible, and Z10 could be a potential anti-CRC agent.
BIOORGANIC CHEMISTRY
(2023)
Review
Medicine, Research & Experimental
Russel J. Reiter, Ramaswamy Sharma, Carmen Rodriguez, Vanesa Martin, Sergio Rosales-Corral, Debora Aparecida Pires de Campos Zuccari, Luiz Gustavo de Almeida Chuffa
Summary: This paper explores the relationship between endogenous melatonin and solid tumors, highlighting the potential of using melatonin to influence cancer cell metabolism. It suggests that solid tumors exhibit a healthier metabolic state at night, potentially reducing proliferation and invasiveness. The paper also proposes using melatonin in a time-sensitive treatment paradigm and combining it with traditional chemotherapy for improved outcomes in cancer treatment.
Article
Plant Sciences
Min Yang, GouYan Hou, YuTing Peng, LiangXin Wang, XiaoYang Liu, YuYan Jiang, CaiXia He, MuSha She, ManTong Zhao, Qing Chen, Mengyao Li, Yong Zhang, Yuanxiu Lin, Yunting Zhang, Yan Wang, Wen He, Xiaorong Wang, Haoru Tang, Ya Luo
Summary: Citric acid is the main organic acid affecting the taste of strawberry fruit. This study found that the overexpression of certain enzymes inhibits fruit ripening and citric acid accumulation, while the overexpression of another enzyme promotes fruit ripening and reduces citric acid content. Transcriptome and metabolome analysis revealed some related metabolic pathways. In conclusion, these enzymes play an important role in regulating citric acid content in strawberry fruit.
FRONTIERS IN PLANT SCIENCE
(2023)
Article
Oncology
Esther P. Jane, Daniel R. Premkumar, Dhivyaa Rajasundaram, Swetha Thambireddy, Matthew C. Reslink, Sameer Agnihotri, Ian F. Pollack
Summary: This study demonstrates that targeting aurora kinases with tozasertib can effectively inhibit cell growth and migration in high-grade glioma cell lines, leading to cell death. However, sustained exposure to tozasertib can result in drug resistance, with upregulation of PDK genes playing a crucial role in the emergence of resistance.
MOLECULAR ONCOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Raquel Vaz, Josephine Wincent, Najla Elfissi, Kristina Rosengren Forsblad, Maria Pettersson, Karin Naess, Anna Wedell, Anna Wredenberg, Anna Lindstrand, Sofia Ygberg
Summary: This study reported a de novo heterozygous missense variant in the PDK1 gene in a girl with developmental delay and early onset severe epilepsy. Using a zebrafish model, the study showed the impact of this variant on energy metabolism and neuronal development, and the possible mechanism behind the clinical symptoms.
Article
Multidisciplinary Sciences
Shaoyan Gao, Xiaohe Li, Qiuyan Jiang, Qing Liang, Fangxia Zhang, Shuangling Li, Ruiqin Zhang, Jiaoyan Luan, Jingyan Zhu, Xiaoting Gu, Ting Xiao, Hui Huang, Shanshan Chen, Wen Ning, Guang Yang, Cheng Yang, Honggang Zhou
Summary: Our study demonstrates that PKM2 promotes fibrosis progression by interacting with Smad7 and enhancing TGF-beta 1 signaling. Increased expression of PKM2 in the lungs of mice with pulmonary fibrosis contributes to fibrosis development. The PKM2 tetramer enhances TGF-beta 1 signaling by directly binding with Smad7, making it a key factor in fibrosis progression.
Article
Multidisciplinary Sciences
Yuko Katayama, Yayoi Kawata, Yusuke Moritoh, Masanori Watanabe
Summary: This study investigated the antidiabetic effect of PDK inhibition using DCA and found that it can effectively lower blood glucose levels, suggesting its potential value in the treatment of diabetes.
Article
Biochemistry & Molecular Biology
Sung-Jin Kim, Yong Taek Jeong, Se Rok Jeong, Munsu Park, Hye Sun Go, Mi Young Kim, Je Kyung Seong, Ki Woo Kim, Jeong Taeg Seo, Chul Hoon Kim, Ji Hyun Lee, Seok Jun Moon
EXPERIMENTAL AND MOLECULAR MEDICINE
(2020)
Article
Biochemistry & Molecular Biology
Yu-Ji Kim, Ki-Sun Kim, Daejin Lim, Dong Ju Yang, Jae-Il Park, Ki Woo Kim, Jae-Ho Jeong, Hueng-Sik Choi, Don-Kyu Kim
Article
Biochemistry & Molecular Biology
Dong Joo Yang, Sang Hyun Moh, Yun-Hee Choi, Ki Woo Kim
Article
Medicine, Research & Experimental
Ji Su Sun, Dong Joo Yang, Ann W. Kinyua, Seul Gi Yoon, Je Kyung Seong, Juwon Kim, Seok Jun Moon, Dong Min Shin, Yun-Hee Choi, Ki Woo Kim
Summary: The dysfunction of primary cilia in the ventromedial hypothalamus is linked to impaired energy and skeletal homeostasis, resulting in obesity and increased bone density. Dysfunction of VMH primary cilia leads to decreased sympathetic activation and central leptin resistance, impacting energy expenditure and bone metabolism.
JOURNAL OF CLINICAL INVESTIGATION
(2021)
Article
Biochemistry & Molecular Biology
Linh V. Nguyen, Khoa D. A. Nguyen, Chi-Thanh Ma, Quoc-Thai Nguyen, Huong T. H. Nguyen, Dong-Joo Yang, Trung Le Tran, Ki Woo Kim, Khanh V. Doan
Summary: p-Coumaric acid potentially activates peripheral AMPK and improves glucose metabolism, while showing inhibitory effects on central AMPK activity. This differential effect enhances hypothalamic leptin sensitivity and improves whole-body glucose homeostasis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell Biology
Sue Young Oh, Namju Kang, Jung Yun Kang, Ki Woo Kim, Jong-Hoon Choi, Yu-Mi Yang, Dong Min Shin
Summary: This study revealed that Sestrin2 plays a crucial role in bone homeostasis and osteoclast differentiation by regulating NFATc1 and the TRAF6/p62 interaction in the RANKL-RANK-TRAF6 signaling pathway. The deletion of Sestrin2 led to a decrease in osteoclast differentiation and function, as well as reduced bone mass, suggesting its novel role in bone metabolism.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Dong Joo Yang, Jessica Hong, Ki Woo Kim
Summary: Obesity is a global health issue associated with metabolic disorders like cardiovascular disease and type 2 diabetes, often caused by metabolic imbalance from lack of physical activity and excessive energy intake. Primary cilia in the hypothalamus are being recognized for their role in regulating energy balance, with defects in ciliary proteins linked to various metabolic disorders. Studying primary cilia in the hypothalamus could offer insights into the central nervous system's role in energy balance and potentially lead to new approaches in preventing and treating obesity and metabolic diseases.
EXPERIMENTAL AND MOLECULAR MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Anish Ashok Adpaikar, Sushan Zhang, Hyun-Yi Kim, Ki Woo Kim, Seok Jun Moon, Jong-Min Lee, Han-Sung Jung
Summary: In this study, a suspension-culture method was established to fine-tune taste bud organoids by altering their apicobasal polarity, enabling the accessible localization of taste receptor cells. These suspension-cultured organoids showed comparable differentiation and renewal rates to those of taste buds in vivo, and exhibited functional taste receptor cells and cycling progenitor cells. This method provides an efficient model for taste research, including taste bud development, regeneration, and transplantation.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Biology
Douglas Ngatuni, Peninah Wairagu, Ngalla Jillani, Alfred Orina Isaac, James Nyabuga Nyariki
Summary: This study investigated the impact of glyphosate-based herbicides (GBH) on vital organs in mice and the potential protective effects of vitamin B12 supplementation. The results showed that vitamin B12 attenuated the GBH-induced anemia, platelet and white blood cell abnormalities, elevation of triglycerides and HDL, oxidative stress, and inflammation. These findings provide evidence for further research on the role of GBH exposure and potent antioxidant supplementation in managing GBH-induced toxicity.
SAUDI JOURNAL OF BIOLOGICAL SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Dhananjay Yadav, Peninah M. Wairagu, Minseok Kwak, Jun-O Jin
Summary: This article discusses the use of nanoparticles in the treatment of pulmonary diseases, highlighting their unique properties and activities in biomedical and pharmaceutical industries. It also emphasizes recent advances in the use of nanoparticles for inhalation chemotherapy.
CURRENT DRUG METABOLISM
(2022)
Article
Biochemistry & Molecular Biology
Hong Phuong Nguyen, Seungheon Shin, Kyung-Ju Shin, Phuong Hoa Tran, Hyungsun Park, Quang De Tran, Mi-Hyun No, Ji Su Sun, Ki Woo Kim, Hyo-Bum Kwak, Seongju Lee, Steve K. Cho, Su-Geun Yang
Summary: This study investigated the effects of microgravity on retinal function in ARPE19 cells. The findings showed that microgravity conditions led to the formation of multicellular spheroids and significantly decreased cell migration in ARPE19 cells. It was also observed that microgravity increased intracellular reactive oxygen species and caused mitochondrial dysfunction. Activation of autophagic pathways and ciliogenesis were also observed under microgravity conditions. Furthermore, it was demonstrated that mitophagy activation was triggered via the mTOR-ULK1-BNIP3 signaling axis. TPP-Niacin was shown to effectively mitigate microgravity-induced oxidative stress and mitochondrial dysfunction in vitro. Further investigations are needed to understand the physiological functions and biological efficacies of TPP-Niacin in primary human retinal cells, in vivo models, and target identification.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
(2023)
Article
Chemistry, Multidisciplinary
Jimin Jeon, Hyemi Lee, Min-Seung Jeon, Seok-Jung Kim, Cham Choi, Ki Woo Kim, Dong Joo Yang, Sangho Lee, Yong-Soo Bae, Won Il Choi, Juyeon Jung, Seong-il Eyun, Siyoung Yang
Summary: The upregulation of ACVR2B and its assembly play a role in osteoarthritic cartilage destruction. Activin A, the ligand for ACVR2B, regulates catabolic factor expression in OA development. The ACVR2B assembly, consisting of Activin A, ACVR2B, ACVR1B, Nox4, and AP-1-induced HIF-2 alpha, accelerates OA development.
Article
Multidisciplinary Sciences
Seul Ki Kim, Le Trung Tran, Cherl NamKoong, Hyung Jin Choi, Hye Jin Chun, Yong-ho Lee, MyungHyun Cheon, ChiHye Chung, Junmo Hwang, Hyun-Ho Lim, Dong Min Shin, Yun-Hee Choi, Ki Woo Kim
Summary: Small humanin-like peptide 2 (SHLP2), a mitochondrial-derived peptide, plays a crucial role in energy homeostasis. The study demonstrates that SHLP2 can protect mice from high-fat diet-induced obesity and improve insulin sensitivity. It activates pro-opiomelanocortin (POMC) neurons in the hypothalamus, which suppresses food intake and promotes thermogenesis. The researchers also discover that SHLP2 binds to and activates chemokine receptor 7 (CXCR7).
NATURE COMMUNICATIONS
(2023)
Review
Biochemistry & Molecular Biology
Le Trung Tran, Sohee Park, Seul Ki Kim, Jin Sun Lee, Ki Woo Kim, Obin Kwon
Summary: The hypothalamus plays a crucial role in controlling energy expenditure and metabolism, influencing lean to fatty tissue ratio, gender-based metabolic differences, activity levels, and weight gain in response to food intake. Further research is needed to unravel cause-and-effect relationships and genetic factors involved in metabolic regulation.
EXPERIMENTAL AND MOLECULAR MEDICINE
(2022)
Article
Pharmacology & Pharmacy
Namju Kang, Ki Woo Kim, Dong Min Shin
KOREAN JOURNAL OF PHYSIOLOGY & PHARMACOLOGY
(2019)