Article
Physiology
Jieun Seo, Jeong-Eun Yun, Sung Joon Kim, Yang-Sook Chun
Summary: Cancer cells adapt to nutrient- and oxygen-deprived environments by rewiring metabolic processes, such as glucose metabolism and lipid metabolism, to promote their proliferation and metastasis. The hypoxia-inducible factor-1 (HIF-1) is a master transcription factor that plays a crucial role in mediating these metabolic alterations. Targeting lipid metabolism by HIF-1 has potential therapeutic implications for cancer treatment.
PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY
(2022)
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)
Review
Pharmacology & Pharmacy
Chunying Xiao, Sheng Liu, Ge Ge, Hao Jiang, Liezhi Wang, Qi Chen, Chong Jin, Jinggang Mo, Jin Li, Kunpeng Wang, Qianqian Zhang, Jianyu Zhou
Summary: Hepatocellular carcinoma (HCC) is a common digestive malignancy and a leading cause of cancer mortality worldwide. Local ablation therapies, such as radiofrequency ablation (RFA) and high-intensity focused ultrasound (HIFU) ablation, have shown effectiveness in treating HCC. However, the molecular mechanisms and HCC recurrence after ablation still need further understanding.
FRONTIERS IN PHARMACOLOGY
(2023)
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
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)
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
Cinthia C. Alves, Eduardo A. Donadi, Silvana Giuliatti
Summary: In hypoxic conditions, HIF1 interacts with the HLA-G gene, leading to higher HLA-G expression, particularly when binding with the -964G allele. The complex formed by HIF1 binding to HRE with the -964G allele is more stable due to the formation of more hydrogen bonds and van der Waals contacts.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Zhaowu Ma, Louis Zizhao Wang, Jun-Ting Cheng, Walter Sze Tung Lam, Xiang Ma, Xiaoqiang Xiang, Andrea Li-Ann Wong, Boon Cher Goh, Quan Gong, Gautam Sethi, Lingzhi Wang
Summary: Hypoxia plays a crucial role in the tumor microenvironment, correlating with tumor metastasis and prognosis. HIF-1α, a key molecule, is involved in multiple crucial steps in the metastatic cascade. Currently, researchers are focusing on potential pharmacological interventions and developing HIF-1 inhibitors to block tumor metastasis.
ANTIOXIDANTS & REDOX SIGNALING
(2021)
Article
Biology
Xiaowei Zheng, Sampath Narayanan, Cheng Xu, Sofie Eliasson Angelstig, Jacob Grunler, Allan Zhao, Alessandro Di Toro, Luciano Bernardi, Massimiliano Mazzone, Peter Carmeliet, Marianna Del Sole, Giancarlo Solaini, Elisabete A. Forsberg, Ao Zhang, Kerstin Brismar, Tomas A. Schiffer, Neda Rajamand Ekberg, Ileana Ruxandra Botusan, Fredrik Palm, Sergiu-Bogdan Catrina
Summary: Excessive production of mitochondrial reactive oxygen species (ROS) in diabetes complications is mainly caused by impaired responses to hypoxia due to the inhibition of hypoxia-inducible factor-1 (HIF-1) by hyperglycemia. Restoring HIF-1 function can attenuate ROS overproduction, protect cells against apoptosis and renal injury in diabetes. These findings suggest that targeting HIF-1 repression could be a potential therapeutic strategy for diabetic complications.
Article
Environmental Sciences
Meriam N. N. Rezk, Gerges M. Beshreda, Dalia Abdelrahman Meshref, Walaa Yehia Abdelzaher, Gaber El-Saber Batiha, Amin A. Hafiz, Duaa Althumairy, Nada H. Aljarba, Nermeen N. Welson
Summary: This study aimed to investigate the role of hypoxiainducible factor-1 alpha (HIF-1 alpha) in the diagnosis, prediction, and follow-up of Dormex-intoxicated patients. The results showed that HIF-1 alpha can effectively predict and follow up patients within 24 hours after admission. Additionally, blood-related indicators were also significantly abnormal in patients with Dormex intoxication.
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
(2023)
Article
Biochemistry & Molecular Biology
Zaira Rehman, Ishrat Jabeen, Ammad Fahim, Attya Bhatti, Peter John
Summary: A ligand-based pharmacophore model was developed to identify potential HIF-1α and β dimerization inhibitors, resulting in the identification of six hits with potential anti-cancer chemotherapy activity. These compounds could serve as potential inhibitors of HIF-1 dimerization after further structure optimization.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Article
Toxicology
Michael Aschner, Anatoly V. Skalny, Rongzhu Lu, Abel Santamaria, Ji-Chang Zhou, Tao Ke, Mikhail Yu. Karganov, Aristides Tsatsakis, Kirill S. Golokhvast, Aaron B. Bowman, Alexey A. Tinkov
Summary: This review summarizes the existing data on the effects of toxic metals on HIF-1 signaling and its underlying mechanisms, with a special focus on the prooxidant effect of metals. The effect of metals on HIF-1 pathway varies depending on the cell type, ranging from down-regulation to up-regulation. Inhibition of HIF-1 signaling may contribute to hypoxic damage in cells, while metal-induced activation may promote tumor growth and contribute to the carcinogenic effects of heavy metals.
ARCHIVES OF TOXICOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Ioanna E. Stergiou, Konstantinos Kambas, Aikaterini Poulaki, Stavroula Giannouli, Theodora Katsila, Aglaia Dimitrakopoulou, Veroniki Vidali, Vasileios Mouchtouris, Ismini Kloukina, Evangelia Xingi, Stamatis N. Pagakis, Lesley Probert, George P. Patrinos, Konstantinos Ritis, Athanasios G. Tzioufas, Michael Voulgarelis
Summary: Myelodysplastic syndromes (MDS) involve a group of disorders affecting hematopoietic stem and progenitor cells, with a particular focus on the role of the transcription factor HIF-1. Aberrant HIF-1 stabilization and pseudohypoxia are prominent features in MDS pathobiology, showing potential for therapeutic manipulation in benign cases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Je Lin Sieow, Hweixian Leong Penny, Sin Yee Gun, Ling Qiao Tan, Kaibo Duan, Joe Poh Sheng Yeong, Angela Pang, Diana Lim, Han Chong Toh, Tony Kiat Hon Lim, Edgar Engleman, Olaf Rotzschke, Lai Guan Ng, Jinmao Chen, Suet Mien Tan, Siew Cheng Wong
Summary: A large number of neutrophils infiltrate tumors and contribute to the inflammatory tumor microenvironment. The metabolic status of these neutrophils and their role in tumor progression were investigated in a mouse model of pancreatic ductal adenocarcinoma (PDAC). Tumor-infiltrating neutrophils showed enhanced glycolytic activity compared to neutrophils from the bone marrow and blood of the same mouse. Deletion of hypoxia-inducible factor 1-alpha (HIF-1 alpha) in neutrophils reduced tumor burden and improved survival in the mouse model, indicating a potential target for metabolic modulation in cancer.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biology
Milica Mandic, Kaitlyn Flear, Pearl Qiu, Yihang K. Pan, Steve F. Perry, Kathleen M. Gilmour
Summary: HIF-1α is important for hypoxic survival in zebrafish, particularly in relation to their ability to perform aquatic surface respiration (ASR). When zebrafish are prevented from accessing the surface during severe hypoxia, their survival is significantly compromised. However, when they are allowed to access the surface, there is no difference in survival between wild-type and HIF-1α knockout fish. ASR mitigates the negative effects of HIF-1α loss, with knockouts initiating ASR at a higher oxygen concentration and performing ASR for longer than wild-types.
PROCEEDINGS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES
(2022)