Six transmembrane protein of prostate 2 (STAMP2) plays a key role in linking inflammatory and diet-derived signals to systemic metabolism. STAMP2 is induced by nutrients/feeding as well as by cytokines such as TNFalpha, IL-1beta, and IL-6. Here, we demonstrated that STAMP2 protein physically interacts with and decreases the stability of hepatitis B virus X protein (HBx), thereby counteracting HBx-induced hepatic lipid accumulation and insulin resistance. STAMP2 suppressed the HBx-mediated transcription of lipogenic and adipogenic genes. Furthermore, STAMP2 prevented HBx-induced degradation of IRS1 protein, which mediates hepatic insulin signaling, as well as restored insulin-mediated inhibition of gluconeogenic enzyme expression, which are gluconeogenic genes. We also demonstrated reciprocal expression of HBx and STAMP2 in HBx transgenic mice. These results suggest that hepatic STAMP2 antagonizes HBx-mediated hepatocyte dysfunction, thereby protecting hepatocytes from HBV gene expression.
Animals ; Female ; Gene Expression ; Gluconeogenesis/genetics ; Hep G2 Cells ; Humans ; Insulin/pharmacology/physiology ; Insulin Receptor Substrate Proteins/genetics/metabolism ; Insulin Resistance ; *Lipid Metabolism ; Liver/*metabolism/physiopathology ; Male ; Membrane Proteins/metabolism/*physiology ; Mice ; Mice, Inbred C57BL ; Mice, Inbred CBA ; Mice, Transgenic ; Oxidoreductases/metabolism/*physiology ; Phosphorylation ; Protein Binding ; Protein Processing, Post-Translational ; Proteolysis ; Receptor, Insulin/metabolism ; Trans-Activators/*physiology ; Transcriptional Activation

Small heterodimer partner (SHP) is an atypical member of nuclear receptor superfamily that lacks a DNA-binding domain. In previous study, we showed that SHP, c-jun, p65 of NF-kappaB subunits, and p21WAF1 expression was increased during monocytic differentiaton with the exposure of human leukemia cells to a differentiation agent, PMA. In this study, c-Jun and p65 were shown to mediate the transcriptional activation of the SHP promoter. In addition, SHP induced the cell cycle regulatory protein levels and cooperatively increased an induction of p21WAF1 expression with p65. Furthermore, SHP protected differentiated cells from etoposide-induced cellular apoptosis through the induction and cytoplasmic sequestration of p21WAF1. Complex formation between SHP and p21WAF1 was demonstrated by means of coimmunoprecipitation. These results suggest that SHP prolongs a cellular survival of differentiating monocytes through the transcriptional regulation of target genes of cell survival and differentiation.
*Apoptosis ; Cell Differentiation ; Cell Line, Tumor ; Cyclin-Dependent Kinase Inhibitor p21/genetics/*metabolism ; Gene Expression Regulation ; Humans ; Monocytes/cytology ; Promoter Regions, Genetic ; Proto-Oncogene Proteins c-jun/genetics/metabolism ; Receptors, Cytoplasmic and Nuclear/genetics/*metabolism ; Transcription Factor RelA/genetics/metabolism

As most individuals acquire immunity to severe acute respiratory syndrome coronavirus 2, South Korea declared a return to normalcy a few months ago. However, epidemic waves continue because of endlessly emerging variants and waning immunity. Health authorities are focusing on those at high risk of severe coronavirus disease 2019 to minimize damage to public health and the economy. In this regard, we investigated the vaccination rates in patients with various chronic medical conditions by examining the national health insurance claims data and the national immunization registry. We found that patients with chronic medical conditions, especially those of higher severity, such as malignancy, had vaccination rates approximately 10–20% lower than those of the general population. Public health authorities and healthcare providers should try to vaccinate these patients to avoid preventable morbidity and mortality.

The thioredoxin (Trx) system plays critical roles in regulating intracellular redox levels and defending organisms against oxidative stress. Recent studies indicated that Trx reductase (TrxR) was overexpressed in various types of human cancer cells indicating that the Trx-TrxR system may be a potential target for anti-cancer drug development. This study investigated the synergistic effect of auranofin, a TrxR-specific inhibitor, on sulforaphane-mediated apoptotic cell death using Hep3B cells. The results showed that sulforaphane significantly enhanced auranofin-induced apoptosis by inhibiting TrxR activity and cell proliferation compared to either single treatment. The synergistic effect of sulforaphane and auranofin on apoptosis was evidenced by an increased annexin-V-positive cells and Sub-G1 cells. The induction of apoptosis by the combined treatment caused the loss of mitochondrial membrane potential (ΔΨm) and upregulation of Bax. In addition, the proteolytic activities of caspases (-3, -8, and -9) and the degradation of poly (ADP-ribose) polymerase, a substrate protein of activated caspase-3, were also higher in the combined treatment. Moreover, combined treatment induced excessive generation of reactive oxygen species (ROS). However, treatment with N-acetyl-L-cysteine, a ROS scavenger, reduced combined treatment-induced ROS production and apoptosis. Thereby, these results deduce that ROS played a pivotal role in apoptosis induced by auranofin and sulforaphane. Furthermore, apoptosis induced by auranofin and sulforaphane was significantly increased through inhibition of the phosphoinositide 3-kinase (PI3K)/Akt pathway. Taken together, the present study demonstrated that down-regulation of TrxR activity contributed to the synergistic effect of auranofin and sulforaphane on apoptosis through ROS production and inhibition of PI3K/Akt signaling pathway.