Key to the transduction of signals from the environment to the cell nucleus are enzymes that post-translationally modify proteins. Modifications such as protein phosphorylation have long been known to regulate protein interactions, stability, and localization, as well as enzyme activity. Recent investigations into how cells respond to varying oxygen levels have identified a new mechanism for regulating signal transduction involving the post-translational hydroxylation of proline. The enzymes that catalyze this reaction comprise a novel family of prolyl hydroxylases, which include a growth-factor-responsive and cell-death-related protein (SM-20) in mammals, and a protein (EGL-9) in C. elegans important for normal egg laying.
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Int J Mol Sci
January 2025
Research Center for High Altitude Medicine, Qinghai University, Xining 810016, China.
The hypoxia-inducible factor (HIF) pathway has been demonstrated to play a pivotal role in the process of high-altitude adaptation. PHD2, a key regulator of the HIF pathway, has been found to be associated with erythropoiesis. However, the relationship between changes in Phd2 abundance and erythroid differentiation under hypoxic conditions remains to be elucidated.
View Article and Find Full Text PDFJ Orthop Surg Res
January 2025
Department of Rehabilitation Medicine, Northern Jiangsu People's Hospital, Yangzhou, Jiangsu, 225001, China.
Objective: To explore the mechanism of hyperbaric oxygen therapy in inhibiting subchondral bone angiogenesis and delaying the progression of osteoarthritis through the PHD2/HIF-1α signaling pathway.
Methods: Mice were randomly divided into three groups (control group, osteoarthritis group, and hyperbaric oxygen treatment group). The effect of hyperbaric oxygen therapy on osteoarthritis was evaluated using Micro-CT, Safranin O-Fast Green staining, and detection of osteoarthritis inflammation markers (MMP-13, ADAMTS-5, Col2a1, and Aggrecan).
Sci Rep
January 2025
Shri Dharmasthala Manjunatheshwara (SDM) University, Manjushree Nagar, Sattur, Dharwad, Karnataka, 580009, India.
In oxygen-deprived conditions, cells respond by activating adaptive mechanisms to bolster their survival and protect tissue integrity. A key player in this process is the HIF-1α signaling cascade, meticulously regulated by Prolyl Hydroxylase Domain 2 (PHD2), which orchestrates cellular responses to varying oxygen levels. The primary aim of this investigation is to utilize gut siderophores as inhibitors of PHD2 in ischemic conditions.
View Article and Find Full Text PDFFEBS J
December 2024
Department of Colorectal Surgery, New Taipei Municipal Tucheng Hospital, Taiwan.
Hypoxia is a critical microenvironmental factor that induces tumorigenesis and cancer progression, including metastasis. The highly dynamic nature of the extracellular matrix (ECM) plays a crucial role in metastasis. Collagens are the predominant component of structural proteins embedded within the ECM.
View Article and Find Full Text PDFSci Transl Med
December 2024
Cell Biology and Biophysics Unit, European Molecular Biology Laboratory, 69117 Heidelberg, Germany.
Excessive deposition of fibrillar collagen in the interstitial extracellular matrix (ECM) of human lung tissue causes fibrosis, which can ultimately lead to organ failure. Despite our understanding of the molecular mechanisms underlying the disease, no cure for pulmonary fibrosis has yet been found. We screened a drug library and found that dextromethorphan (DXM), a cough expectorant, reduced the amount of excess fibrillar collagen deposited in the ECM in cultured primary human lung fibroblasts, a bleomycin mouse model, and a cultured human precision-cut lung slice model of lung fibrosis.
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