Background: Clinical trials evaluating the use of steroids in septic shock have shown variable outcomes. Our previous studies have implicated human glucocorticoid receptor (hGR) polymorphisms as a possible cause of altered steroid response. To further evaluate this variability, we hypothesized that hGR polymorphisms along with type of steroid influence the functional response.
Methods: Total RNA was isolated from healthy human blood samples and surveyed for the hGR gene. The National Center for Biotechnology Information hGRα sequence was used as a reference, and two unique single nucleotide polymorphisms (SNPs) (A214G and T962C) were selected for evaluation. Functional response was measured using a luciferase reporting assay after transfecting hGR isoforms into tsA201 cells and stimulation with graded concentrations of hydrocortisone (HYD), methylprednisolone (MPS), and dexamethasone (DEX).
Results: Each isoform had a unique dose-response curve with the optimal activity depending on concentration and type of steroid. The presence of either SNP A214G or T962C resulted in a decreased response when compared with hGRα when stimulated with HYD (P < 0.01). The same decreased response occurred for the SNPs with DEX stimulation, but at a much lower concentration range than HYD (P < 0.01). However, in the presence of MPS, SNP A214G resulted in greater activity when compared with hGRα (P < 0.01), whereas the presence of T962C resulted in activity equivalent to hGRα.
Conclusions: SNPs, type of steroid, and concentration range impact the functional response of the hGR. A greater understanding of hGR polymorphisms and steroid response may further elucidate mechanisms explaining the variable response seen with patient treatment.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.jss.2012.12.027 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Phagocytic clearance of apoptotic cancer cells (efferocytosis) by tumor-associated macrophages (TAMs) contributes in a substantial manner to the establishment of an immunosuppressive tumor microenvironment. This puts in context our observation that the female steroid hormone 17β-estradiol (E2) facilitates tumor immune resistance through cancer cell extrinsic Estrogen Receptor (ERalpha;) signaling in TAMs. Notable was the finding that E2 induces the expression of CX3CR1 in TAMs to enable efferocytosis of apoptotic cancer cells which results in the suppression of type I interferon (IFN) signaling.
View Article and Find Full Text PDFEffect of PCSK9 inhibitor on early neurological deterioration in acute ischemic stroke patients with a history of coronary heart disease: a study protocol for a randomized controlled trial in Dalian, China.
Trials
January 2025
Department of Neurology, the First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning Province, China.
Background: Early neurological deterioration (END) is a critical determinant influencing the short-term prognosis of acute ischemic stroke (AIS) patients and is associated with increased mortality rates among hospitalized individuals. AIS frequently coexists with coronary heart disease (CHD), complicating treatment and leading to more severe symptoms and worse outcomes. Shared risk factors between CHD and AIS, especially elevated low-density lipoprotein cholesterol (LDL-C), contribute to atherosclerosis and inflammation, which worsen brain tissue damage.
View Article and Find Full Text PDFNPC1 controls TGFBR1 stability in a cholesterol transport-independent manner and promotes hepatocellular carcinoma progression.
Nat Commun
January 2025
State Key Laboratory of Medical Proteomics, National Center for Protein Sciences (Beijing), Beijing Proteome Research Center, Beijing Institute of Lifeomics, Beijing, China.
Niemann-Pick disease type C protein 1 (NPC1), classically associated with cholesterol transport and viral entry, has an emerging role in cancer biology. Here, we demonstrate that knockout of Npc1 in hepatocytes attenuates hepatocellular carcinoma (HCC) progression in both DEN (diethylnitrosamine)-CCl induced and MYC-driven HCC mouse models. Mechanistically, NPC1 significantly promotes HCC progression by modulating the TGF-β pathway, independent of its traditional role in cholesterol transport.
View Article and Find Full Text PDFEffects of implant status and breed type on feedlot performance, carcass characteristics, sera metabolites, and immunohistochemical responses in finishing steers.
J Anim Sci
January 2025
Department of Animal and Food Sciences, Texas Tech University, Lubbock, TX USA.
The number of beef × dairy animals entering feedlots has increased, but the response of beef × dairy cattle to growth-promoting implants has not been well characterized. The objective of this study was to evaluate the effects of breed type and implant administration on live performance, carcass characteristics, sera metabolites, and immunohistochemical (IHC) outcomes. Forty-eight steers (average body weight [BW] = 417±22 kg) were sorted by breed into groups of predominantly Angus (B), black-hided beef × primarily Holstein (B×D), or Holstein (D), and half of the steers within each breed type were administered a steroidal implant.
View Article and Find Full Text PDFIncidence and risk factors for acute kidney injury in children with nephrotic syndrome: a meta-analysis.
Front Pediatr
December 2024
Department of Pediatrics, The First Hospital of Quanzhou Affiliated to Fujian Medical University, Quanzhou, Fujian, China.
Background: Nephrotic syndrome (NS) is a prevalent kidney disease in children. Acute kidney injury (AKI) is a severe complication of NS and has the potential to be life-threatening.
Objective: The aim of this study was to analyze the prevalence and risk factors of AKI in children with NS, and to provide an evidence-based medical basis for the early identification of high-risk children in the clinic.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!