Last update 01 Nov 2024

DENR

Last update 01 Nov 2024

Basic Info

Synonyms

DENR, density regulated re-initiation and release factor, Density-regulated protein

+ [5]

Introduction

May be involved in the translation of target mRNAs by scanning and recognition of the initiation codon. Involved in translation initiation; promotes recruitmnet of aminoacetyled initiator tRNA to P site of 40S ribosomes. Can promote release of deacylated tRNA and mRNA from recycled 40S subunits following ABCE1-mediated dissociation of post-termination ribosomal complexes into subunits. Plays a role in the modulation of the translational profile of a subset of cancer-related mRNAs when recruited to the translational initiation complex by the oncogene MCTS1.

Drugs associated with DENR

IR-418

Target

DENR x ERK

Mechanism

DENR inhibitors [+1]

Active Org.

Southwest Medical University

Originator Org.

Southwest Medical University

Active Indication

Melanoma

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

MDIVI-1

Target

DENR

Mechanism

DENR inhibitors

Active Org.

University of Louisville

Originator Org.

University of Louisville

Active Indication

Perioperative ischaemia [+1]

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

ASHA-091

Target

DENR x UTRN

Mechanism

DENR inhibitors [+1]

Active Org.

Asha Therapeutics LLCStartup

Originator Org.

Asha Therapeutics LLCStartup

Active Indication

Amyotrophic Lateral Sclerosis [+3]

Inactive Indication

Fatigue Syndrome, Chronic [+1]

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with DENR

100 Translational Medicine associated with DENR

0 Patents (Medical) associated with DENR

130

Literatures (Medical) associated with DENR

01 Nov 2024·Journal of Applied Toxicology

Isoflurane preconditioning attenuates OGD/R‐induced cardiomyocyte cytotoxicity by regulating the miR‐210/BNIP3 axis

Article

Author: Wu, Qiaoling ; Dai, Siqi ; Zhang, Dongbo ; Shen, Tu ; Liu, Feifei

AbstractIsoflurane, a commonly used inhaled anesthetic, has been found to have a cardioprotective effect. However, the precise mechanisms have not been fully elucidated. Here, we found that isoflurane preconditioning enhanced OGD/R‐induced upregulation of miR‐210, a hypoxia‐responsive miRNA, in AC16 human myocardial cells. To further test the roles of miR‐210 in regulating the effects of isoflurane preconditioning on OGD/R‐induced cardiomyocyte injury, AC16 cells were transfected with anti‐miR‐210 or control anti‐miRNA. Results showed that isoflurane preconditioning attenuated OGD/R‐induced cardiomyocyte cytotoxicity (as assessed by cell viability, LDH and CK‐MB levels), which could be reversed by anti‐miR‐210. Isoflurane preconditioning also prevented OGD/R‐induced increase in apoptotic rate, caspase‐3 and caspase‐9 activities, and Bax level and decrease in Bcl‐2 expression level, while anti‐miR‐210 blocked these effects. We also found that anti‐miR‐210 prevented the inhibitory effects of isoflurane preconditioning on OGD/R‐induced decrease in adenosine triphosphate content; mitochondrial volume; citrate synthase activity; complex I, II, and IV activities; and p‐DRP1 and MFN2 expression. Besides, the expression of BNIP3, a reported direct target of miR‐210, was significantly decreased under hypoxia condition and could be regulated by isoflurane preconditioning. In addition, BNIP3 knockdown attenuated the effects of miR‐210 silencing on the cytoprotection of isoflurane preconditioning. These findings suggested that isoflurane preconditioning exerted protective effects against OGD/R‐induced cardiac cytotoxicity by regulating the miR‐210/BNIP3 axis.

01 Nov 2024·Biochemical Pharmacology

Exendin-4 exhibits cardioprotective effects against high glucose-induced mitochondrial abnormalities: Potential role of GLP-1 receptor and mTOR signaling

Article

Author: Mangmool, Supachoke ; Pandey, Sudhir ; Parichatikanond, Warisara

Mitochondrial dysfunction is associated with hyperglycemic conditions and insulin resistance leading to cellular damage and apoptosis of cardiomyocytes in diabetic cardiomyopathy. The dysregulation of glucagon-like peptide-1 (GLP-1) receptor and mammalian target of rapamycin (mTOR) is linked to cardiomyopathies and myocardial dysfunctions mediated by hyperglycemia. However, the involvements of mTOR for GLP-1 receptor-mediated cardioprotection against high glucose (HG)-induced mitochondrial disturbances are not clearly identified. The present study demonstrated that HG-induced cellular stress and mitochondrial damage resulted in impaired ATP production and oxidative defense markers such as catalase and SOD2, along with a reduction in survival markers such as Bcl-2 and p-Akt, while an increased expression of pro-apoptotic marker Bax was observed in H9c2 cardiomyoblasts. In addition, the autophagic marker LC3-II was considerably reduced, together with the disruption of autophagy regulators (p-mTOR and p-AMPKα) under the hyperglycemic state. Furthermore, there was a dysregulated expression of several indicators related to mitochondrial homeostasis, including MFN2, p-DRP1, FIS1, MCU, UCP3, and Parkin. Remarkably, treatment with either exendin-4 (GLP-1 receptor agonist) or rapamycin (mTOR inhibitor) significantly inhibited HG-induced mitochondrial damage while co-treatment of exendin-4 and rapamycin completely reversed all mitochondrial abnormalities. Antagonism of GLP-1 receptors using exendin-(9-39) abolished these cardioprotective effects of exendin-4 and rapamycin under HG conditions. In addition, exendin-4 attenuated HG-induced phosphorylation of mTOR, and this inhibitory effect was antagonized by exendin-(9-39), indicating the regulation of mTOR by GLP-1 receptor. Therefore, improvement of mitochondrial dysfunction by stimulating the GLP-1 receptor/AMPK/Akt pathway and inhibiting mTOR signaling could ameliorate cardiac abnormalities caused by hyperglycemic conditions.

01 Oct 2024·Biotechnology and Applied Biochemistry

Ohwia caudata inhibits doxorubicin‐induced cardiotoxicity by regulating mitochondrial dynamics via the IGF‐IIR/p‐Drp1/PARP signaling pathway

Article

Author: Kuo, Chia‐Hua ; Islam, Md. Nazmul ; Kuo, Wei‐Wen ; Ramesh, Samiraj ; Chen, Jhong‐Kuei ; Shibu, Marthandam Asokan ; Lin, Shinn‐Zong ; Ho, Tsung‐Jung ; Huang, Chih‐Yang ; Hsieh, Dennis Jine‐Yuan

AbstractThe most effective drug, doxorubicin (DOX), is widely used worldwide for clinical application as an anticancer drug. DOX‐induced cytotoxicity is characterized by mitochondrial dysfunction. There is no alternative treatment against DOX‐induced cardiac damage despite intensive research in the present decades. Ohwia caudata has emerged as a potential herbal remedy that prevents from DOX‐induced cytotoxicity owing to its pharmacological action of sustaining mitochondrial dynamics by attenuating oxidative stress and inducing cellular longevity. However, its underlying mechanisms are unknown. The novel treatment provided here depends on new evidence from DOX‐treated H9c2 cells, which significantly enhanced insulin‐like growth factor (IGF) II receptor (IGF‐IIR) pathways that activated calcineurin and phosphorylated dynamin‐related protein 1 (p‐Drp1) at ser616 (p‐Drp1[ser616]); cells undergo apoptosis due to these factors, which translocate to mitochondria and disrupt their function and integrity, and in terms of herbal medicine treatment, which significantly blocked these phenomena. Thus, our findings indicate that maintaining integrity of mitochondria is an essential element in lowering DOX‐induced cytotoxicity, which further emphasizes that our herbal medicine can successfully block IGF‐IIR pathways and could potentially act as an alternative mechanism in terms of cardioprotective against doxorubicin.

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DENR

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