Abstract:
:Although GHRH and GHRH-R are recognized as key factors in placental development, little is known about the mechanism(s) of the regulation in trophoblastic cells during placental development. The objective of this study is to determine the potential relationship between the expression levels of GHRH-R and the placental and JEG-3 cell function. Furthermore, we aim to investigate the downstream pathways of GHRH/GHRH-R axis in the control of the JEG-3 cell viability and apoptosis. In this study, we detected the expression pattern of GHRH-R in human chorionic villous tissues and JEG-3 cell. Then, we evaluated the effects of GHRH/GHRH-R and the downstream pathways by using GHRH antagonist (JMR-132) on JEG-3 cell. Our present study found the expressions of GHRH-R in placental villous tissues and JEG-3 cell, and the expression levels of GHRH-R was significantly lower in villous tissues of early pregnancy loss when compared to normal controls. JMR-132 inhibited cellular viability and induced apoptosis in JEG-3 cell in a time and dosedependent manners through activation of caspase-3, p38, and p53, as well as inhibition of phosphorylation of Akt. Interestingly, ER stress markers such as GRP78, ubiquitinated proteins and phospho-eIF2α were significantly increased in JEG-3 cell after being treated with JMR-132. Conversely, pretreated with salubrinal (a selective inhibition of protein phosphatase 1-mediated eIF2α dephosphorylation), JEG-3 cells were rescued from JMR-132-mediated cell growth inhibition, and abolished JMR-132-induced cleaved caspase-3, CHOP, phospho-p53, and ubiquitinated proteins accumulation. Knockdown of endogenous GHRH-R significantly abolished the JMR-132-induced cleaved caspase-3 and activation of p38. In conclusion, our results, for the first time, demonstrated the expression levels of GHRH-R were closely related to the placental function. Inhibition of GHRH-R by using GHRH antagonist in JEG-3 cell may reduce cell viability and induce apoptosis through inactivation of Akt and ER stress via phosphorylation of eIF2α. These observations have enriched our understanding on the function of GHRH/GHRH-R axis and the downstream pathways in the control of the placental development. The Most Important Aspect of the Paper: Our present study for the first time provided evidences that GHRH and GHRH-R loops involve in JEG-3 cell viability and apoptosis through Akt and eIF2α pathways.
journal_name
Curr Mol Medjournal_title
Current molecular medicineauthors
Liu AX,Zhang D,Zhu YM,Gao HJ,Jiang JY,Hu XL,Lv PP,Leung PC,Huang HFdoi
10.2174/1566524016666160225154040subject
Has Abstractpub_date
2016-01-01 00:00:00pages
299-311issue
3eissn
1566-5240issn
1875-5666pii
CMM-EPUB-73971journal_volume
16pub_type
杂志文章abstract:OBJECTIVE:This study aims to investigate the effect of morphine with naloxone on intestinal peristalsis and the number of interstitial cells of Cajal (ICC) in colon tissues of rabbits. METHODS:Thirty rabbits were randomly divided into five groups (n=6, each group): saline control group (NS group), low concentration of...
journal_title:Current molecular medicine
pub_type: 杂志文章
doi:10.2174/1566524019666191023112837
更新日期:2020-01-01 00:00:00
abstract::Type 1 diabetes (T1D) is an organ-specific autoimmune disease resulting from the specific destruction of insulin-producing pancreatic beta-cells, culminating in a state of hypoinsulinemia and hyperglycemia. Pathogenesis of T1D comprises complex series of events from the initial sensitization of antigen-presenting cell...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/156652409787314471
更新日期:2009-02-01 00:00:00
abstract:BACKGROUND:Liver kinase B1 (LKB1)/5'-adenosine monophosphate-activated protein kinase (AMPK) signaling, a metabolic checkpoint, plays a neuro-protective role in the pathogenesis of Alzheimer's disease (AD). Amyloid-β (Aβ) acts as a classical biomarker of AD. The aim of the present study was to explore whether berberine...
journal_title:Current molecular medicine
pub_type: 杂志文章
doi:10.2174/1566524019666190315164120
更新日期:2019-01-01 00:00:00
abstract::HMGB1/Amphoterin is a ubiquitous, highly conserved DNA-binding protein that can be also released to the extracellular space by various cell types. Extracellular HMGB1 regulates migratory responses of several cell types through binding to RAGE that communicates with the cytoskeleton to regulate cell motility. HMGB1-ind...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/156652407783220750
更新日期:2007-12-01 00:00:00
abstract::Skeletal mass is regulated by the coordinated action of bone forming osteoblasts and bone resorbing osteoclasts. Accelerated rates of bone resorption relative to bone formation lead to net bone loss and the development of osteoporosis, a devastating disease that predisposes the skeleton to fractures. Bone fractures ar...
journal_title:Current molecular medicine
pub_type: 杂志文章
doi:10.2174/1566524014666140724104842
更新日期:2014-01-01 00:00:00
abstract:BACKGROUND:Macrophages undergo polarization or activation in response to environmental stimuli, an essential process for proper immune response. Meanwhile, excessive activation of macrophages causes autoimmune diseases. It is therefore crucial to prevent over-activation of macrophage in order to maintain the proper imm...
journal_title:Current molecular medicine
pub_type: 杂志文章
doi:10.2174/1566524017666171106114537
更新日期:2017-12-07 00:00:00
abstract::Focal cerebral ischemia induces neurogenesis in the subventricular zone (SVZ) of the adult human brain. Neurogenesis is controlled by proliferation, differentiation, and migration of neural progenitor cells. This article reviews emerging data that changes of cell cycle kinetics of neural progenitor cells induced by st...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/156652407781387136
更新日期:2007-08-01 00:00:00
abstract::The blood stage of the malaria parasite's life cycle is responsible for all the clinical symptoms of malaria. The development of clinical disease is dependent on the interplay of the infecting parasite with the immune status and genetic background of the host. Following repeated exposure to malaria parasites, individu...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/156652406776055212
更新日期:2006-03-01 00:00:00
abstract::Non-alcoholic fatty liver disease (NAFLD) is a clinico-pathologic spectrum of conditions ranging from simple steatosis to nonalcoholic steatohepatitis (NASH). Although simple or bland steatosis follows a relatively benign clinical course, NASH can potentially progress to cirrhosis (approximately 10 to 15 percent) and ...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/156652410790963321
更新日期:2010-03-01 00:00:00
abstract::Human genetic data on psychiatric disorders repeatedly demonstrate the involvement of various genes that are associated with neural development and neurogenesis. Neurogenesis is a biological process that is critical in brain development and continues throughout life. Neurogenesis is a multi-step process starting from ...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/1566524015666150303002834
更新日期:2015-01-01 00:00:00
abstract::Citrate is one of the major substrates for intracellular metabolism. The extracellular level of citrate is stable in blood but varies locally, with slightly increased levels in brain and high levels in prostate. Recent metabolomics research suggests that citrate level is a potential harbinger of different pathophysiol...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/1566524016666151123104855
更新日期:2015-01-01 00:00:00
abstract::Most lysosomal storage diseases (LSD) exhibit neurological symptoms and there has been limited success in their treatment. Innovative treatments employing novel therapy or gene therapy may offer the prospect of improvement. Recent attempts to treat the neurological forms of LSD include neural stem cell therapy, mesenc...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/1566524023363112
更新日期:2002-02-01 00:00:00
abstract:BACKGROUND & OBJECTIVE:Interleukin 37 (IL-37) is an important regulator of the anti-inflammatory T-cell response. In this study, we investigated its expression and function in peripheral blood mononuclear cells (PBMCs) of patients with HLA-B27 associated acute anterior uveitis (AAU) and idiopathic AAU. METHODS:15 pati...
journal_title:Current molecular medicine
pub_type: 杂志文章
doi:10.2174/1566524018666180207152941
更新日期:2018-03-09 00:00:00
abstract::Despite advances in biomedical sciences, the prognosis of patients with brain tumors remains poor. Effective treatment is lacking for these central nervous system (CNS) cancers. Targeted immunotoxins are a new class of therapeutic approaches that have emerged for the treatment of human cancers. In this approach, tumor...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/156652409788970661
更新日期:2009-08-01 00:00:00
abstract:OBJECTIVES:Celastrol, a quinone methide triterpenoid, could induce apoptosis in pancreatic cancer cells. The purpose of this study is to determine whether there is protective autophagy after celastrol treatment in pancreatic cancer cells and the synergistic effects of celastrol and 3-MA in vitro and in vivo. METHODS:T...
journal_title:Current molecular medicine
pub_type: 杂志文章
doi:10.2174/1566524014666140414211223
更新日期:2014-05-01 00:00:00
abstract:BACKGROUND:Overexpression of MDA-9/Syntenin occurs in multiple human cancer cell lines and is associated with higher grade of tumor classification, invasiveness and metastasis. In some cases, its role in cancer biology depends on relationships between MDA-9/Syntenin and NF-κB. OBJECTIVE:This study aims to analyze the ...
journal_title:Current molecular medicine
pub_type: 杂志文章
doi:10.2174/1566524019666190104105043
更新日期:2018-01-01 00:00:00
abstract:BACKGROUND:In this study, the antioxidant property of new synthesized azomethins has been investigated as theoretical and experimental. METHODS AND RESULTS:Density functional theory (DFT) was employed to investigate the Bond Dissociation Enthalpy (BDE), Mulliken Charges, NBO analysis, Ionization Potential (IP), Electr...
journal_title:Current molecular medicine
pub_type: 杂志文章
doi:10.2174/1566524019666190509102620
更新日期:2019-01-01 00:00:00
abstract::Inhibition of tumor angiogenesis suppresses tumor growth and metastatic spreading in many experimental models, suggesting that anti-angiogenic drugs may be used to treat human cancer. During the past decade more than eighty molecules that showed anti-angiogenic activity in preclinical studies were tested in clinical c...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/1566524033479410
更新日期:2003-12-01 00:00:00
abstract:PURPOSE:To evaluate cytokine expression profile in aqueous humor and sera in patients with HLAB27 associated acute anterior uveitis (AAU) and idiopathic AAU. METHODS:Twenty patients with AAU and 17 controls were recruited from August 2012 to March 2013. Study subjects with uveitis were divided into two groups: 9 patie...
journal_title:Current molecular medicine
pub_type: 杂志文章
doi:10.2174/1566524015666150731100012
更新日期:2015-01-01 00:00:00
abstract::Asthma, chronic obstructive pulmonary disorder (COPD), and cystic fibrosis (CF), chronic diseases of the airways, are characterized by symptoms such as inflammation of the lung tissue, mucus hypersecretion, constriction of the airways, and excessive fibrosis of airway tissue. Transforming growth factor (TGF)-beta, a c...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/156652408785160943
更新日期:2008-08-01 00:00:00
abstract::The central role of glutamate receptors in mediating excitotoxic neuronal death in stroke, epilepsy and trauma has been well established. Glutamate is the major excitatory amino acid transmitter within the CNS and it's signaling is mediated by a number of postsynaptic ionotropic and metabotropic receptors. Although ca...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/1566524043479202
更新日期:2004-03-01 00:00:00
abstract::Although it has been known for long time that atherosclerosis is associated with lipid deposition, only recently it has been accepted that the plasmatic concentration of cholesterol, especially LDL cholesterol, is a risk factor for atherosclerosis. However, chemically modified LDL, but not native LDL, is able to induc...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/1566524023362177
更新日期:2002-09-01 00:00:00
abstract::The view that mitochondrial electron transport is the only site of aerobic respiration and the primary bioenergetic pathway in mammalian cells is well established in the literature. Although this paradigm is widely accepted for most tissues, the situation is less clear for proliferating cells. Increasing evidence indi...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/156652406779010777
更新日期:2006-12-01 00:00:00
abstract::Peroxisomal proliferator activated receptor gamma (PPARgamma) belongs to the family of nuclear hormone receptors (NHRs), which directly regulate transcription of target genes. The regulatory role of this receptor on lipid metabolism and insulin sensitization is well established. Recently, the overexpression of this re...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/156652407781695765
更新日期:2007-09-01 00:00:00
abstract::Osteopontin (OPN) is a matricellular protein that is produced by multiple tissues in our body and is most abundant in bone. It is also produced by cancer cells and plays a determinative role in the growth, progression and metastasis of cancer. Clinically, OPN has been reported to be upregulated in tumor cells per se; ...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/156652410791065381
更新日期:2010-02-01 00:00:00
abstract::Prostate cancer is one of the most difficult cancers to treat especially when it becomes hormone resistant such as castrate resistant prostate cancer (CRPC) and subsequent metastatic CRPC. Apart from the genetic alterations in prostate cancer, epigenetic modifications also play an important role in the development and...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/1566524018666171219101937
更新日期:2017-01-01 00:00:00
abstract::Chondroitin sulfate (CS)-glycosaminoglycans (GAGs) are linear, negatively charged polysaccharides attached to CS proteoglycans that make up a major component of biological matrices throughout both central and peripheral tissues. The position of their attached sulfate groups to the CS disaccharide is predicted to influ...
journal_title:Current molecular medicine
pub_type: 杂志文章
doi:10.2174/1566524020666200915110707
更新日期:2020-09-15 00:00:00
abstract::Tumor-derived exosomes contain biological contents such as proteins, lipids, RNA (miRNAs, mRNAs, lncRNA), and DNA for intracellular communication. Meanwhile, studies have shown the role of exosomes in cancer progression, metastasis, and therapeutic resistance. Furthermore, tumor exosomes have received growing attentio...
journal_title:Current molecular medicine
pub_type: 杂志文章
doi:10.2174/1566524020666201120142953
更新日期:2020-11-20 00:00:00
abstract:BACKGROUND:The phenotypic severity of β-thalassemia is highly modulated by three genetic modifiers: β-globin (HBB) mutations, co-inheritance of α-thalassemia and polymorphisms in the genes associated with fetal haemoglobin (HbF) production. This study was aimed to evaluate the effect of HbF related polymorphisms mainly...
journal_title:Current molecular medicine
pub_type: 临床试验,杂志文章
doi:10.2174/1566524018666181004121604
更新日期:2018-01-01 00:00:00
abstract::Germline mutations in the VHL tumour suppressor gene may cause a variety of phenotypes including von Hippel-Lindau (VHL) disease, familial phaeochromocytoma and inherited polycythaemia. VHL disease is a multisystem familial cancer syndrome and is the commonest cause of familial renal cell carcinoma (RCC). VHL disease ...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/1566524043359827
更新日期:2004-12-01 00:00:00