Last update 01 Nov 2024

P4HA

Last update 01 Nov 2024

Basic Info

Synonyms-

Introduction-

Drugs associated with P4HA

Safironil

Target

P4HA

Mechanism

P4HA inhibitors

Active Org.-

Originator Org.

Sanofi

Active Indication-

Inactive Indication

Liver Cirrhosis

Drug Highest PhaseDiscontinued

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

Lufironil

Target

P4HA

Mechanism

P4HA inhibitors

Active Org.-

Originator Org.

Sanofi

Active Indication-

Inactive Indication

Fibrosis [+2]

Drug Highest PhaseDiscontinued

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with P4HA

100 Translational Medicine associated with P4HA

0 Patents (Medical) associated with P4HA

Literatures (Medical) associated with P4HA

01 May 2024·Physiologia Plantarum

Biochemical characterization and metabolic reprogramming of amino acids in Soybean roots under drought stress

Article

Author: Wang, Xiyue ; Li, Xiaomei ; Dong, Shoukun

AbstractAmino acids play important roles in stress resistance, plant growth, development, and quality, with roots serving as the primary organs for drought response. We conducted biochemical and multi‐omics analyses to investigate the metabolic processes of root amino acids in drought‐resistant (HN44) and drought‐sensitive (HN65) soybean (Glycine max) varieties. Our analysis revealed an increase in total amino acid content in both varieties, with phenylalanine, proline, and methionine accumulating in both. Additionally, several amino acids exhibited significant decreases in HN65 but slight increases in HN44. Multi‐omics association analysis identified 13 amino acid‐related pathways. We thoroughly examined the changes in genes and metabolites involved in various amino acid metabolism/synthesis and determined core genes and metabolites through correlation networks. The phenylalanine, tyrosine, and tryptophan metabolic pathways and proline, glutamic acid and sulfur‐containing amino acid pathways were particularly important for drought resistance. Some candidate genes, such as ProDH and P4HA family genes, and metabolites, such as O‐acetyl‐L‐serine, directly affected up‐ and downstream metabolism to induce drought resistance. This study provided a basis for soybean drought resistance breeding.

01 Jul 2023·Hepatology

P4HA2 induces hepatic ductular reaction and biliary fibrosis in chronic cholestatic liver diseases

Article

Author: Lian, Min ; Ma, Xiong ; Peng, Yanshen ; Chen, Ruiling ; Gershwin, M Eric ; Xiao, Xiao ; Lyu, Zhuwan ; Fang, Jingyuan ; Li, You ; Cui, Nana ; Tang, Ruqi ; Li, Yikang ; Zhang, Jun ; Huang, Bingyuan ; Wang, Qixia ; Miao, Qi ; You, Zhengrui ; Li, Bo ; Chen, Yong

Backgrounds:Prolyl-4-hydroxylases (P4Hs) are key enzymes in collagen synthesis. The P4HA subunit (P4HA1, P4HA2, and P4HA3) contains a substrate binding and catalyzation domain. We postulated that P4HA2 would play a key role in the cholangiocyte pathology of cholestatic liver diseases.Methods:We studied humans with primary biliary cholangitis (PBC) and Primary sclerosing cholangitis (PSC), P4HA2-/- mice injured by DDC, and P4HA2-/-/MDR2-/- double knockout mice. A parallel study was performed in patients with PBC, PSC, and controls using immunohistochemistry and immunofluorescence. In the murine model, the level of ductular reaction and biliary fibrosis were monitored by histology, qPCR, immunohistochemistry, and Western blotting. Expression of Yes1 Associated Transcriptional Regulator (YAP) phosphorylation was measured in isolated mouse cholangiocytes. The mechanism of P4HA2 was explored in RBE and 293T cell lines by using qPCR, Western blot, immunofluorescence, and co-immunoprecipitation.Results:The hepatic expression level of P4HA2 was highly elevated in patients with PBC or PSC. Ductular reactive cholangiocytes predominantly expressed P4HA2. Cholestatic patients with more severe liver injury correlated with levels of P4HA2 in the liver. In P4HA2-/- mice, there was a significantly reduced level of ductular reaction and fibrosis compared with controls in the DDC-induced chronic cholestasis. Decreased liver fibrosis and ductular reaction were observed in P4HA2-/-/MDR2-/- mice compared with MDR2-/- mice. Cholangiocytes isolated from P4HA2-/-/MDR2-/- mice displayed a higher level of YAP phosphorylation, resulting in cholangiocytes proliferation inhibition. In vitro studies showed that P4HA2 promotes RBE cell proliferation by inducing SAV1 degradation, eventually resulting in the activation of YAP.Conclusions:P4HA2 promotes hepatic ductular reaction and biliary fibrosis by regulating the SAV1-mediated Hippo signaling pathway. P4HA2 is a potential therapeutic target for PBC and PSC.

01 Jul 2023·Comparative Biochemistry and Physiology Part C: Toxicology & Pharmacology

Characterization of a novel prolyl hydroxylase 2 gene from mud crab Scylla paramamosain: Insights into its role in the regulation of hypoxia-inducible factor-1α

Article

Author: Cheng, Chang-Hong ; Fan, Si-Gang ; Guo, Zhi-Xun ; Jie, Yu-Kun ; Feng, Juan ; Ma, Hong-Ling ; Liu, Guang-Xin ; Jiang, Jian-Jun

Prolyl hydroxylase 2 (PHD2) is the key oxygen sensor that regulates the stability of the hypoxia-inducible factor -1α (HIF-1α). In this study, a novel PHD2 gene from the mud crab Scylla paramamosain, named SpPHD2, was cloned and identified. The full-length transcript of SpPHD2 was found to be 1926 bp, consisting of a 333 bp 5' untranslated region, a 1239 bp open reading frame, and a 354 bp 3' untranslated region. The putative SpPHD2 protein contained a Prolyl 4-hydroxylase alpha subunit homologues (P4Hc) domain in the C-terminal and a Myeloid translocation protein 8, Nervy, and DEAF-1 (MYND)-type zinc finger (zf-MYND) domain in the N-terminal. The mRNA expression of SpPHD2 was found to be widely distributed across all examined tissues. Additionally, the subcellular localization results indicated that the SpPHD2 protein was mainly localized in the cytoplasm. The in vivo silencing of SpPHD2 resulted in the upregulation of SpHIF-1α and a series of downstream genes involved in the HIF-1 pathway, while SpPHD2 overexpression in vitro dose-dependently reduced SpHIF-1α transcriptional activity, indicating that SpPHD2 plays a crucial role in SpHIF-1α regulation. Interestingly, the expression of SpPHD2 increased under hypoxic conditions, which was further inhibited by SpHIF-1α interference. Moreover, four hypoxia response elements were identified in the SpPHD2 promoter, suggesting that a feedback loop exists between SpPHD2 and SpHIF-1α under hypoxia. Taken together, these results provided new insights into the regulation of SpPHD2 in response to hypoxia in S. paramamosain.

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P4HA

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