Last update 01 Nov 2024

PDHA1

Last update 01 Nov 2024

Basic Info

Synonyms

PDHA, PDHA1, PDHE1-A type I

+ [3]

Introduction

The pyruvate dehydrogenase complex catalyzes the overall conversion of pyruvate to acetyl-CoA and CO(2), and thereby links the glycolytic pathway to the tricarboxylic cycle.

Drugs associated with PDHA1

CN117159693

Patent Mining

Target

PDHA1

Mechanism-

Active Org.

Mianyang Third People's Hospital

Originator Org.

Mianyang Third People's Hospital

Active Indication

Neoplasms

Inactive Indication-

Drug Highest PhaseDiscovery

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with PDHA1

100 Translational Medicine associated with PDHA1

0 Patents (Medical) associated with PDHA1

618

Literatures (Medical) associated with PDHA1

01 Jan 2025·Journal of Ethnopharmacology

Hippocampal PDHA1 gene knockout inhibits the Warburg effect leading to cognitive dysfunction and attenuates the beneficial effects of ZiBuPiYin recipe on cognition

Article

Author: Bi, Tingting ; Tang, Zhijuan ; Zhan, Libin ; Li, Yuan ; Zhou, Wen ; Lu, Linfeng

ETHNOPHARMACOLOGICAL RELEVANCEThe attenuation of the Warburg effect is an important pathological feature of cognitive dysfunction, and enhancing the Warburg effect is conducive to improving cognitive function. However, the pathogenic mechanisms underlying cognitive dysfunction remain incompletely elucidated. ZiBuPiYin Recipe (ZBPYR) is a traditional Chinese herbal compound used clinically for the treatment of cognitive dysfunction with significant efficacy. Nonetheless, the molecular mechanism underlying its beneficial effects remains elusive.AIM OF THE STUDYThe objective of this study is to investigate whether the attenuation of the Warburg effect exists in a mouse model of cognitive dysfunction induced by knockout of the pyruvate dehydrogenase E1 component subunit alpha (PDHA1) gene in the hippocampus, as well as the interventional effect of ZBPYR.MATERIALS AND METHODSUsing mice with PDHA1 gene knockout in the hippocampus and their littermate control mice as study subjects, behavioral experiments were conducted to assess the impact of PDHA1 gene knockout on cognitive function and the interventional effect of ZBPYR. We detected the expression of the Warburg effect-associated rate-limiting enzymes and PI3K/AKT pathway-related proteins. Subsequently, in PC12 cells, we explored the effect of the Warburg effect on cell apoptosis as well as the role of PDHA1 in the regulation of the PI3K/AKT-Warburg effect and the potential mechanism of ZBPYR in improving cognitive function.RESULTSMice with knockout of the PDHA1 gene in the hippocampus exhibited cognitive dysfunction, inhibition of the PI3K/AKT pathway, reduction of the Warburg effect, and neuronal damage. In vitro experiments indicated that silencing of PDHA1 in the hippocampus inhibited the PI3K/AKT-Warburg effect, leading to cell apoptosis and mediated the effect of ZBPYR in improving cognitive function.CONCLUSIONOur data not only suggest that the hippocampal PDHA1-PI3K/AKT-Warburg effect may be involved in the pathogenesis of cognitive dysfunction, but also demonstrate that PDHA1 knockout can abolish the beneficial effects of ZBPYR on cognition. This research aids in unraveling the cause of cognitive dysfunction and, therefore, offers a promising and innovative therapeutic target for these patients.

31 Dec 2024·Gynecological Endocrinology

Enhanced glycolysis in the myometrium with ectopic endometrium of patients with adenomyosis: a preliminary study

Article

Author: Liu, Shanjia ; Guan, Yongge ; Huang, Shiya ; Liu, Xuehong ; Huang, Xueqian ; Li, Kunyin ; Ma, Hongxia ; Wang, Yishu ; Xie, Linling ; Wen, Xiaohui

OBJECTIVESThe objective of this study was to investigate the glycolytic activity of adenomyosis, which is characterized by malignant biological behaviors including abnormal cell proliferation, migration, invasion, cell regulation, and epithelial-mesenchymal transition.METHODSFrom January 2021 to August 2022, a total of 15 patients who underwent total hysterectomy for adenomyosis and 14 patients who had non-endometrial diseases, specifically with cervical squamous intraepithelial neoplasia and uterine myoma, were included in this study. Myometrium with ectopic endometrium from patients with adenomyosis while normal myometrium from patients in the control group were collected. All samples were confirmed by a histopathological examination. The samples were analyzed by liquid chromatography-mass spectrometry (LC-MS), real-time quantitative PCR, NAD+/NADH assay kit as well as the glucose and lactate assay kits.RESULTSEndometrial stroma and glands could be observed within the myometrium of patients in the adenomyosis group. We found that the mRNA expressions of HK1, PFKFB3, glyceraldehyde-3-phospate dehydrogenase (GAPDH), PKM2, and PDHA as well as the protein expressions of PFKFB3 were elevated in ectopic endometrial tissues of the adenomyosis group as compared to normal myometrium of the control group. The level of fructose 1,6-diphosphate was increased while NAD + and NAD+/NADH ratio were decreased compared with the control group. Besides, increased glucose consumption and lactate production were observed in myometrium with ectopic endometrium.CONCLUSIONSWe concluded that altered glycolytic phenotype of the myometrium with ectopic endometrium in women with adenomyosis may contribute the development of adenomyosis.

31 Dec 2024·Renal Failure

Comprehensive analysis of cuproptosis-related genes in immune infiltration and development of a novel diagnostic model for acute kidney injury

Article

Author: Li, Yajing ; Ding, Yingxue

BACKGROUNDAcute kidney injury (AKI) represents a diverse range of conditions characterized by high incidence and mortality rates, and it is mainly associated with immune-mediated mechanisms and mitochondrial metabolism dysfunction. Cuproptosis, a recently identified form of programmed cell death dependent on copper, is closely linked to mitochondrial respiration and contributes to various diseases. Our study aimed to investigate the involvement of cuproptosis-related genes (CRGs) in AKI.METHODSIdentification of CRGs was conducted using differential expression analysis, and subsequent Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted using human sequencing profiles. Utilizing CIBERSORT algorithm, receiver operating characteristic (ROC) curve analysis, nomogram development, and decision curve analysis (DCA), the association among immune scores, CRGs, and the diagnostic value of these genes was explored.RESULTSNotably, six CRGs (FDX1, DLD, DLAT, DBT, PDHA1, and ATP7A) were identified as significant differentiators between AKI and non-AKI groups. The ROC curve, based on these six genes, demonstrated an AUC value of 0.917, which was further validated using an additional dataset with an AUC value of 0.902. Nomogram and DCA further confirmed the accuracy of the model in predicting the risk of AKI.CONCLUSIONThis study elucidated the role of cuproptosis in AKI and revealed the association between CRGs and infiltrated immune cells through comprehensive bioinformatic techniques. The six-gene cuproptosis-related signature exhibited remarkable predictive efficiency for AKI.

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