Article
Cell Biology
Bo Zhang, Yan Chen, Lei Bao, Weibo Luo
Summary: This study demonstrates that hypoxia upregulates the expression of GPT2 in GBM cells through HIF-2 activation. GPT2 is localized in the nucleus and mitochondria and can decrease α-ketoglutarate levels in GBM cells. Inhibition of GPT2 can reduce GBM cell growth and migration, and knockout of GPT2 inhibits GBM tumor growth in mice.
Review
Pharmacology & Pharmacy
Baoqi Yu, Xia Wang, Yanting Song, Guomin Xie, Shiyu Jiao, Li Shi, Xuejie Cao, Xinyao Han, Aijuan Qu
Summary: Cardiovascular diseases are the leading cause of death worldwide, and hypoxia-inducible factors (HIFs) play an important role in their pathogenesis. Recent studies have revealed the role of cell-specific HIFs in various cardiovascular diseases, but the potential clinical application of HIF inhibitors in the treatment of cardiovascular diseases is not well understood.
PHARMACOLOGY & THERAPEUTICS
(2022)
Article
Biochemistry & Molecular Biology
Giorgia F. Camagni, Giovanni Minervini, Silvio C. E. Tosatto
Summary: The Prolyl Hydroxylases (PHDs) are a family of enzymes that regulate cell oxygen-sensing by hydroxylating hypoxia-inducible transcription factors alpha (HIFs-alpha) and promoting their degradation. Hypoxia inhibits PHDs activity, leading to HIFs-alpha stabilization and cell adaptation to low oxygen levels. The different isoforms of PHDs have varying effects on tumor progression. Molecular dynamics simulations, conservation analysis, and binding free energy calculations were used to study the binding properties and substrate affinity of PHD2 with HIF-1 alpha and HIF-2 alpha. The findings suggest that the PHD2 C-terminus may play a role in regulating PHD activity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biotechnology & Applied Microbiology
Wenpeng Cao, Shan Lei, Zhirui Zeng, Chaolun Xiao, Baofei Sun, Peng Xie, Yumei Li, Daopeng Luo, Wenfeng Yu
Summary: This study identified TRAA2A as an important hypoxia-associated gene in pancreatic cancer, which is associated with tumor progression and metastasis. TRAA2A is regulated by hypoxia-inducible factor HIF1 alpha and promotes the proliferation and motility of pancreatic cancer cells via activation of the AKT pathway. Therefore, TRAA2A may serve as a novel molecular target for investigating the hypoxic response of pancreatic cancer cells.
Review
Endocrinology & Metabolism
Rodrigo A. Toledo, Camilo Jimenez, Gustavo Armaiz-Pena, Carlota Arenillas, Jaume Capdevila, Patricia L. M. Dahia
Summary: The HIF2 alpha inhibitor belzutifan has been approved by the FDA as a treatment for certain tumors, opening up a new approach in cancer therapy. This article reviews the molecular rationale and clinical data for HIF2 alpha blockade, as well as discussing potential mutations that may be sensitive to this approach. Resistance mechanisms to HIF2 alpha inhibitors, including acquired mutations in HIF2 alpha and its interacting partner ARNT, are also outlined. The high efficacy of belzutifan in tumors driven by genetic hypoxia suggests that other mutations leading to HIF2 alpha stabilization should be further investigated.
Review
Cell Biology
Elena V. Mitroshina, Maria O. Savyuk, Evgeni Ponimaskin, Maria V. Vedunova
Summary: Hypoxia is a common pathological condition induced by various events, with the body's adaptation to it being crucial for health and disease. HIFs, a family of transcription factors, play a key role in cellular responses to hypoxia and are increasingly viewed as potential targets for treating a range of hypoxia-associated diseases. The role of HIFs in adaptation to hypoxia is universal across tissue types, including the CNS, where they are involved in regulating neurogenesis, nerve cell differentiation, and neuronal apoptosis, potentially offering new therapeutic opportunities.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Biology
Corine M. van der Weele, William R. Jeffery
Summary: Dark caves lacking primary productivity expose subterranean animals to hypoxia. Cavefish cope with hypoxia by increasing erythrocyte development and constitutive hif1 gene overexpression.
Article
Dentistry, Oral Surgery & Medicine
Aoi Takashima, Jiro Miura, Keita Sugiyama, Masato Shimizu, Misa Okada, Tomohiro Otani, Tadashi Nagashima, Tetsuya Tsuda, Tsutomu Araki
Summary: Intrapulpal calcifications can occur in the dental pulp of patients with diabetes. This study focused on the association between ectopic calcifications in the dental pulp and advanced glycation end products (AGEs) in an obese type 2 diabetic rat model. The results indicated that AGEs were strongly expressed in the dental pulp of diabetic rats, and pulpal inflammation was observed. Mechanical pressure and blood flow disorder were also factors contributing to intrapulpal calcification.
Article
Oncology
Jiao Xue, Chenxiao Yu, Yiting Tang, Wei Mo, Zhicheng Tang, Wenjiong Sheng, Yang Jiao, Wei Zhu, Jianping Cao
Summary: Nrf2 overexpression protects against radiation-induced skin injury by regulating genes involved in the reactive oxygen species pathway.
FRONTIERS IN ONCOLOGY
(2021)
Article
Urology & Nephrology
Szu-Yu Pan, Pei-Zhen Tsai, Yu-Hsiang Chou, Yu-Ting Chang, Fan-Chi Chang, Yen-Ling Chiu, Wen-Chih Chiang, Tien Hsu, Yung-Ming Chen, Tzong-Shinn Chu, Shuei-Liong Lin
Summary: PHD inhibitors are effective in treating CKD-associated anemia by stabilizing HIF and increasing erythropoiesis. However, their impact on kidney fibrosis is inconsistent due to the context-dependent effects of HIF. Studies on pericytes suggest that HIF stabilization in these cells may not negatively affect kidney fibrosis despite increased erythropoietin production.
KIDNEY INTERNATIONAL
(2021)
Article
Biochemistry & Molecular Biology
Zhonghua Luo, Tao Li, Qingqing Gao, Yu Chen, Guangyue Su, Yuqing Zhao
Summary: The study demonstrates that LicA has potential protective effects in preventing and treating diabetic nephropathy, reducing blood glucose, improving lipid profiles, and enhancing renal function. Additionally, LicA can ameliorate pathological damage in DN mice, providing a theoretical basis for further development and utilization of LicA.
Review
Pharmacology & Pharmacy
Zirong Pan, Guodong Ma, Linglei Kong, Guanhua Du
Summary: Stroke is an acute cerebrovascular disease caused by sudden rupture or blockage of blood vessels in the brain, and HIF-1 plays an important role in regulating various pathways in the pathological process. The roles of HIF-1 in stroke are controversial, involving factors such as ischemic time and degree, and its regulatory mechanisms include inflammation, autophagy, oxidative stress, and apoptosis.
PHARMACOLOGICAL RESEARCH
(2021)
Article
Cardiac & Cardiovascular Systems
Zhiyu Dai, Jianding Cheng, Bin Liu, Dan Yi, Anlin Feng, Ting Wang, Lingling An, Chen Gao, Yibin Wang, Maggie M. Zhu, Xianming Zhang, You-Yang Zhao
Summary: The study reveals the unexpected role of endothelial PHD2 deficiency in inducing cardiac hypertrophy and fibrosis in an HIF-2 alpha-dependent manner, suggesting it as a potential novel therapeutic approach for treating pathological cardiac hypertrophy and heart failure.
JOURNAL OF THE AMERICAN HEART ASSOCIATION
(2021)
Review
Immunology
Jinwei Zhang, Xiaoqian Wu, Jideng Ma, Keren Long, Jing Sun, Mingzhou Li, Liangpeng Ge
Summary: Hypoxia and HIF signaling have important regulatory roles in cell biology, but their role in B cell biology is still controversial. Studies have found that hypoxia niches exist in different developmental stages of B cells, suggesting that hypoxia and HIF signaling may play a crucial role in the development, metabolism, and function of B cells. A better understanding of the role of hypoxia in B cell-mediated adaptive immunity could provide new strategies for vaccine adjuvant research and the treatment of immunity-related or infectious diseases.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Medicine, Research & Experimental
Min Kyung Park, Jun Ji, Keeok Haam, Tae-Hee Han, Seona Lim, Mi-Jung Kang, Soon Sung Lim, Hyun Seung Ban
Summary: Licochalcone A, a component of Glycyrrhiza uralensis, demonstrates potential as a therapeutic agent in hypoxic cancer cells by inhibiting HIF-1 alpha accumulation and mitochondrial respiration, leading to increased oxygen content and suppression of cancer cell viability.
BIOMEDICINE & PHARMACOTHERAPY
(2021)
