Search

The present study investigated the potential subchronic toxicity of self-assembled-micelle inhibitory RNA-targeting amphiregulin (SAMiRNA-AREG) in mice. The test reagent was administered once-daily by intravenous injection for 4 weeks at 0, 100, 200, or 300 mg/kg/day doses. Additional recovery groups (vehicle control and high dose groups) were observed for a 2-week recovery period. During the test period, mortality, clinical signs, body weight, food consumption, ophthalmology, urinalysis, hematology, serum biochemistry, gross pathology, organ weight, and histopathology were examined. An increase in the percentages of basophil and large unstained cells was observed in the 200 and 300 mg/kg/day groups of both sexes. In addition, the absolute and relative weights of the spleen were higher in males given 300 mg/kg/day relative to the concurrent controls. However, these findings were considered of no toxicological significance because the changes were minimal, were not accompanied by other relevant results (eg, correlating microscopic changes), and were not observed at the end of the 2-week recovery period indicating recovery of the findings. Based on the results, SAMiRNA-AREG did not cause treatment-related adverse effects at dose levels of up to 300 mg/kg/day in mice after 4-week repeated intravenous doses. Under these conditions, the no-observed-adverse-effect level of the SAMiRNA-AREG was ≥300 mg/kg/day in both sexes and no target organs were identified.

The self-assembled-micelle inhibitory RNA-targeting amphiregulin (SAMiRNA-AREG) is a novel small-interfering RNA (siRNA) nanoparticle that is used for treatment of pulmonary fibrosis. We investigated the potential genotoxicity of SAMiRNA-AREG based on the guidelines published by the Organization for Economic Cooperation and Development. In the bacterial reverse mutation assay (Ames test), SAMiRNA-AREG did not induce mutations in

Background The precise diagnosis of dermoid cysts, which are usually located deeper than other common cysts, is important because dermoid cysts occasionally recur after incomplete excision. Ultrasonography (US) could give useful preoperative information of dermoid cysts but only a few studies have been conducted on US findings related to dermoid cysts. This study aimed to investigate clinical and US findings on pediatric dermoid cysts. Methods We retrospectively reviewed the medical records, clinical photographs, and US findings of 31 pediatric patients (≤18 years of age) with histopathologically diagnosed dermoid cysts who visited the Pusan National University Hospital between 2007 and 2016. Results Of the 31 patients, 25 underwent ultrasonography. The mean long diameter, short diameter, and depth of the cysts were 12.7, 9.0, and 3.8 mm, respectively. Sixteen cysts (64%) were ovoid, 23 (92%) showed hypoechogenicity, 20 (80%) showed heterogeneity, 19 (76%) showed well-demarcated outer margins, and all cysts showed positive posterior acoustic enhancement. All cysts extended to the subcutaneous tissue, and 15 (60%) showed a connection with the underlying muscle. Conclusions Ultrasonography may be a useful diagnostic method to visualize the extent and location of the dermoid cyst and make an accurate diagnosis prior to surgical intervention.

Graphical abstract, Highlights • SAMiRNA-AREG is a modified siRNA nanoparticle for treatment of pulmonary fibrosis. • Safety pharmacology of SAMiRNA-AREG was evaluated using core battery studies. • No adverse effects on the neurobehavior, respiratory, and cardiovascular systems. • These data provide important safety data for clinical trials in humans., The present safety pharmacology core battery studies (neurobehavior, respiratory, cardiovascular system, and human ether a-go-go (hERG) channel current) investigated the potential harmful effects of self-assembled-micelle inhibitory RNA-targeting amphiregulin (SAMiRNA-AREG). The SAMiRNA-AREG was administered by single intravenous injection at up to 300 mg/kg and 100 mg/kg in mice and monkeys, respectively. The hERG assay was performed in Chinese hamster ovary (CHO) cells at SAMiRNA-AREG concentrations of up to 200 μg/mL. In the evaluation on neurobehavior, a transient decrease in body temperature was found at 0.5 h (30 min) post-dose at both sexes in mice, with a single 300 mg/kg dose of SAMiRNA-AREG. However, these effects had returned to normal at 1 h post-dose. In the evaluation on hERG channel current, there were statistically significant differences in the inhibition of peak hERG potassium channel current between the 20, 100, and 200 μg/mL SAMiRNA-AREG treatment groups and the vehicle control group. However, these effects were less potent than that of E-4031, a positive control article. For the respiratory and cardiovascular systems, no treatment-related changes were observed in mice or monkeys. Thus, under these experimental conditions, these studies suggest that SAMiRNA-AREG showed no adverse effects on the neurobehavior, respiratory, and cardiovascular function.

Fibrosis is a serious unintended side effect of radiation therapy. In this study, we aimed to investigate whether amphiregulin (AREG) plays a critical role in fibrosis development after total-body irradiation (TBI). We found that the expression of AREG and fibrotic markers, such as α-smooth muscle actin (α-SMA) and collagen type I alpha 1 (COL1α1), was elevated in the kidneys of 6 Gy TBI mice. Expression of AREG and α-SMA was mainly elevated in the proximal and distal tubules of the kidney in response to TBI, which was confirmed by immunofluorescence staining. Knockdown of Areg mRNA using self-assembled-micelle inhibitory RNA (SAMiRNA) significantly reduced the expression of fibrotic markers, including α-SMA and COL1α1, and inflammatory regulators. Finally, intravenous injections of SAMiRNA targeting mouse Areg mRNA (SAMiRNA-mAREG) diminished radiation-induced collagen accumulation in the renal cortex and medulla. Taken together, the results of the present study suggest that blocking of AREG signaling via SAMiRNA-mAREG treatment could be a promising therapeutic approach to alleviate radiation-induced kidney fibrosis.

Amphiregulin (AREG) is a transmembrane glycoprotein recently implicated in kidney fibrosis. Previously, we reported that the AREG-targeting Self-Assembled-Micelle inhibitory RNA (SAMiRNA-AREG) alleviated fibrosis by stably silencing the AREG gene, and reduced the side effects of conventional siRNA treatment of pulmonary fibrosis. However, the therapeutic effect of SAMiRNA-AREG in renal fibrosis has not been studied until now. We used two animal models of renal fibrosis generated by a unilateral ureteral obstruction (UUO) and an adenine diet (AD) to investigate whether SAMiRNA-AREG inhibited renal fibrosis. To investigate the delivery of SAMiRNA-AREG to the kidney, Cy5-labeled SAMiRNA-AREG was injected into UUO- and AD-induced renal fibrosis models. In both kidney disease models, SAMiRNA-AREG was delivered primarily to the damaged kidney. We also confirmed the protective effect of SAMiRNA-AREG in renal fibrosis models. SAMiRNA-AREG markedly decreased the UUO- and AD-induced AREG mRNA expression. Furthermore, the mRNA expression of fibrosis markers, including α-smooth muscle actin, fibronectin, α1(I) collagen, and α1(III) collagen in the UUO and AD-induced kidneys, was diminished in the SAMiRNA-AREG-treated mice. The transcription of inflammatory markers (tumor necrosis factor-α and monocyte chemoattractant protein-1) and adhesion markers (vascular cell adhesion molecule 1 and intercellular adhesion molecule 1) was attenuated. The hematoxylin and eosin, Masson’s trichrome, and immunohistochemical staining results showed that SAMiRNA-AREG decreased renal fibrosis, AREG expression, and epidermal growth factor receptor (EGFR) phosphorylation in the UUO- and AD-induced models. Moreover, we studied the effects of SAMiRNA-AREG in response to TGF-β1 in mouse and human proximal tubule cells, and mouse fibroblasts. TGF-β1-induced extracellular matrix production and myofibroblast differentiation were attenuated by SAMiRNA-AREG. Finally, we confirmed that upregulated AREG in the UUO or AD models was mainly localized in the distal tubules. In conclusion, SAMiRNA-AREG represents a novel siRNA therapeutic for renal fibrosis by suppressing EGFR signals.

We developed the service showing patient health record altogether which is managed by each hospital separately and recording the patient health information based on mobile application. We evaluated the effectiveness and satisfaction of the service. This study is aimed to reduce instances where patient's medical records are unknown to the medical staff in emergencies and allow patients to use and utilize their health information.

We explored gender differences in the characteristics and outcomes of patients with out-of-hospital cardiac arrest (OHCA) in Korea.We retrospectively analyzed a nationwide multicenter registry of out-of-hospital cardiac arrest patients that prospectively collected from January to December 2014, and explored the clinical outcomes of 670 successfully resuscitated adult patients with OHCA who were transferred to 27 hospitals. The effect of gender on the 30-day neurologically favorable survival (cerebral performance category 1 or 2) was analyzed after propensity score matching (PSM) of each patient in terms of clinical characteristics.We included 670 patients with OHCA, of whom 482 (72%) were male and 182 (28%) were female. The frequency of witnessed arrests and proportion of home arrests were similar between men and women (73.7% vs 71.3%, P = .59, and 55.0% vs 60.6% P = .21, respectively). Women were older than men (mean age, 65.9 vs 59.7 years, P .001) and less likely to present with an initial shockable rhythm (27.7% vs 45.0%, P .001). Women were less likely to undergo targeted temperature management (19.1% vs 35.9%, P .001), coronary angiography (14.9% vs 36.1%, P .001), or revascularization (7.4% vs 19.3%, P .001). Compared with men, women exhibited poorer 30-day neurologically favorable survival (69.7% vs 83.0%, P = .001). However, the gender difference was not significant on PSM or inverse probability of treatment weighting (IPTW) analyses (P = .48 and P = .63, respectively).Female patients with OHCA exhibited poorer clinical characteristics and were less likely to receive treatment than men. After accounting for these differences, clinical outcomes did not differ by gender.

Microenvironment, such as hypoxia common to cancer, plays a critical role in the epithelial‐to‐mesenchymal transition (EMT) program, which is a major route of cancer metastasis and confers γ‐radiation resistance to cells. Herein, we showed that transgelin 2 (TAGLN2), an actin‐binding protein, is significantly induced in hypoxic lung cancer cells and that Snail1 is simultaneously increased, which induces EMT by downregulating E‐cadherin expression. Forced TAGLN2 expression induced severe cell death; however, a small population of cells surviving after forced TAGLN2 overexpression showed γ‐radiation resistance, which might promote tumor relapse and recurrence. These surviving cells showed high metastatic activity with an increase of EMT markers including Snail1. In these cells, TAGLN2 activated the insulin‐like growth factor 1 receptor β (IGF1Rβ)/PI3K/AKT pathway by recruitment of focal adhesion kinase to the IGF1R signaling complex. Activation of the IGF1Rβ/PI3K/AKT pathway also induced inactivation of glycogen synthase kinase 3β (GSK3β), which is involved in Snail1 stabilization. Therefore, both the IGF1Rβ inhibitor (AG1024) and the PI3K inhibitor (LY294002) or AKT inactivation with MK2206 lower the cellular level of Snail1. Involvement of GSK3β was also confirmed by treatment with lithium chloride, the inducer of GSK3β phosphorylation, or MG132, the 26S proteasomal inhibitor, which also stabilized Snail1. In conclusion, the present study provides important evidence that hypoxia‐inducible TAGLN2 is involved in the selection of cancer cells with enhanced EMT properties to overcome the detrimental environment of cancer cells.

Polyurethane foam (PUF) is a porous material and significantly affected by compressive loads. Under a uniaxial compressive load, the PUF exhibits various types of material nonlinear behavior under varying conditions, such as density, foaming direction, and strain rate. This study investigates the nonlinear behavior of a PUF through phenomenological approach. A Frank–Brockman–Zairi elasto-viscoplastic constitutive model was adopted to investigate the behavior of PUFs with different densities, directions, and strain rates when subjected to compressive loads. The proposed model was discretized using the implicit time integration algorithm and implemented into a user-defined subroutine of ABAQUS. In this study, parameter determination method was also implemented to identify material parameters containing the constitutive equations. Furthermore, the detailed process of determining the material parameters containing the shape of the work-hardening rate–stress curve dependent on the type of material behavior was presented. Consequently, the macroscopic material response of the PUF, such as the stress–strain curve, can be predicted based on the proposed constitutive model. In future studies, the mechanical behavior of porous materials can be analyzed more successfully by supplementing the constitutive model. This can allow the model to simulate the complex plastic flow of porous materials after yielding that is presently difficult to implement.

The polyurethane foam (PUF) is one of the most widely used composite materials in industrial and biomedical fields. It is frequently adopted in a wide range of environmental conditions, i.e., from static to dynamic compressive loads, and from cryogenic to high temperatures. Under these various environments, the PUF shows an elasto-viscoplastic behavior including three stages of material characteristics, namely, linear elasticity, a plateau with stress drop, and densification. Hence, the establishment of material model as well as the identification of material characteristics is the key of design and fabrication for PUF-based structures. In the present study, the strain rate- and the temperature-dependent elasto-viscoplastic behavior of polyurethane foam (PUF) which is extensively used in various fields and environments was computationally estimated under static/dynamic compression and the low/high temperature. To depict the three stages of material characteristics such as linear elasticity, a plateau with stress drop, and densification under uniaxial compression numerically, a Frank-Brockman type plastic multiplier and a Zairi type hardening-softening internal stress state variable were introduced. Then, the constitutive model was transformed as an implicit form using algorithmic tangential stiffness (ATS) method and was programmed as a user-defined material subroutine of commercial finite element analysis (FEA) code, namely, ABAQUS UMAT. Through the developed material subroutine, the strain rate- and the temperature-dependent static and dynamic stress-strain behaviors were numerically assessed. In addition, the change of material constants such as elastic modulus, yield stress, and hardening and softening control parameters was investigated quantitatively, and the polynomial multiple regression models were suggested. Consequently, the calculated results considerably correspond to experimental results, and through some supplements, accuracy can be improved. On using the proposed numerical method with some revision, it might be possible to anticipate the nonlinear behavior of the unknown material in various strain rate and temperature environment.

본 논문은 2015년도 한국해양과학기술진흥원의 연구과제인 해수면상 승에 대비한 연안사회기반시설 피해저감을 위한 고립파의 처오름높이 연 구비 지원으로 수행하였음(Reference No. 20140437).

Background The analysis of integrated multi-omics data enables the identification of disease-related biomarkers that cannot be identified from a single omics profile. Although protein-level data reflects the cellular status of cancer tissue more directly than gene-level data, past studies have mainly focused on multi-omics integration using gene-level data as opposed to protein-level data. However, the use of protein-level data (such as mass spectrometry) in multi-omics integration has some limitations. For example, the correlation between the characteristics of gene-level data (such as mRNA) and protein-level data is weak, and it is difficult to detect low-abundance signaling proteins that are used to target cancer. The reverse phase protein array (RPPA) is a highly sensitive antibody-based quantification method for signaling proteins. However, the number of protein features in RPPA data is extremely low compared to the number of gene features in gene-level data. In this study, we present a new method for integrating RPPA profiles with RNA-Seq and DNA methylation profiles for survival prediction based on the integrative directed random walk (iDRW) framework proposed in our previous study. In the iDRW framework, each omics profile is merged into a single pathway profile that reflects the topological information of the pathway. In order to address the sparsity of RPPA profiles, we employ the random walk with restart (RWR) approach on the pathway network. Results Our model was validated using survival prediction analysis for a breast cancer dataset from The Cancer Genome Atlas. Our proposed model exhibited improved performance compared with other methods that utilize pathway information and also out-performed models that did not include the RPPA data utilized in our study. The risk pathways identified for breast cancer in this study were closely related to well-known breast cancer risk pathways. Conclusions Our results indicated that RPPA data is useful for survival prediction for breast cancer patients under our framework. We also observed that iDRW effectively integrates RNA-Seq, DNA methylation, and RPPA profiles, while variation in the composition of the omics data can affect both prediction performance and risk pathway identification. These results suggest that omics data composition is a critical parameter for iDRW. Electronic supplementary material The online version of this article (10.1186/s12920-019-0511-x) contains supplementary material, which is available to authorized users.

Background Integrative analysis on multi-omics data has gained much attention recently. To investigate the interactive effect of gene expression and DNA methylation on cancer, we propose a directed random walk-based approach on an integrated gene-gene graph that is guided by pathway information. Methods Our approach first extracts a single pathway profile matrix out of the gene expression and DNA methylation data by performing the random walk over the integrated graph. We then apply a denoising autoencoder to the pathway profile to further identify important pathway features and genes. The extracted features are validated in the survival prediction task for breast cancer patients. Results The results show that the proposed method substantially improves the survival prediction performance compared to that of other pathway-based prediction methods, revealing that the combined effect of gene expression and methylation data is well reflected in the integrated gene-gene graph combined with pathway information. Furthermore, we show that our joint analysis on the methylation features and gene expression profile identifies cancer-specific pathways with genes related to breast cancer. Conclusions In this study, we proposed a DRW-based method on an integrated gene-gene graph with expression and methylation profiles in order to utilize the interactions between them. The results showed that the constructed integrated gene-gene graph can successfully reflect the combined effect of methylation features on gene expression profiles. We also found that the selected features by DA can effectively extract topologically important pathways and genes specifically related to breast cancer.

This paper addresses the system lifetime maximization algorithm in multi-hop sensor network system. A multi-hop sensor network consists of many battery-driven sensor nodes that collaborate with each other to gather, process, and communicate information using wireless communications. As sensor-driven applications become increasingly integrated into our lives, we propose a energy-aware scheme where each sensor node transmits informative data with adaptive data rate to minimize system energy consumption. We show the optimal data rate to maximize the system lifetime in terms of remaining system energy. Furthermore, the proposed algorithm experimentally shows longer system lifetime in comparison with greedy algorithm.

Chemo- or radiation-resistance in tumors caused by hypoxia often undermines efficacy of cancer therapy. Thus, therapies that overcome cellular resistance during hypoxia are necessary. SM22α is an actin-binding protein found in smooth muscle, fibroblasts, and some epithelium. We demonstrate that SM22α is induced in A549 non-small cell lung carcinoma cells by hypoxia and its overexpression increased chemo- and radiation-resistance. Hypoxia-mediated induction of SM22α expression is hypoxia-inducible factor-independent. Moreover, SM22α overexpression enhances tumor cell growth and activates the IGF1R/PI3K/Akt pathway via direct interaction with IGF1Rβ. Our results suggest SM22α as a novel regulator of hypoxic survival pathway of A549 NSCLC cells.Structured summary of protein interactionsIGFR1 Beta physically interacts with SM22 alpha by anti bait coimmunoprecipitation (View Interaction: 1, 2)

High swell is often generated offshore and damages the east coasts of Korea and accidents, a correct prediction of dangerous swells should be done before they approach to the shore. Recently, a warning system to countermeasure dangerous swells is setup on the east coast of Korea with simultaneous in-situ wave measurements at the northeast site of Ulleung offshore island and at Hupo nearshore station. By analyzing these intensive wave observation data and wave prediction model results, detailed swell characteristics are studied in the East coast of Korea. Calculated wave data by the system are compared to the wave data predicted using wind input data and observed wave data at nearshore station.

Fibulin-3, an extracellular glycoprotein, has been suggested as having functions in tissue regeneration and organogenesis. However, its role in cancer remains unclear. We show here that fibulin-3 was silenced by hypermethylation of the promoter region in the relatively invasive A549 non-small cell lung cancer (NSCLC) cells compared with less invasive H460 NSCLC cells. Enforced expression of fibulin-3 in A549 cells down-regulated cellular MMP-7 and MMP-2, which was followed by inhibition of cell invasiveness. Conversely, suppression of fibulin-3 expression with siRNA in H460 cells showed the opposite effect. These results indicate that fibulin-3 is a negative regulator of invasiveness in NSCLC and further studies are needed for its therapeutic applications in treatment of NSCLC.

In battery-operated wireless video surveillance systems (WVSS), it is mostly required to detect events in an energy-efficient manner due to limited available energy and a huge amount of data to be processed. Therefore, one of the main challenges in the battery-constrained systems is to minimize the energy consumption of the whole system. In this paper, we present an energy-aware event detector which has a hierarchical decision architecture to maximize the system lifetime while achieving the required detection accuracy. An analytical model for the relationship between the complexity of the event detector and system performance is derived based on the given event characteristics. Finally, we suggest a heuristic search algorithm to significantly reduce the heavy computational complexity. Experimental results have shown that the proposed heuristic search algorithm provides 98.17% complexity reduction on average with a negligible deterioration of the system lifetime.

A mobile wireless camera (MWC) captures scene as it moves around, and then, stores the scene after compression. In this paper, we propose a novel method to extend battery lifetime by intermittently transmitting the compressed data to the base station (BS) through wireless transmission when the distance between MWC and BS is shorter than a given threshold distance; otherwise, compressed data are stored in the internal memory of MWC. We present an analytic method to determine the threshold distance based on the statistics of transmission distance and available memory capacity such that the lifetime of MWC is maximized while preserving all compressed data. Experimental results show that the proposed resource management method offers up to 79.72% (average 33.57%) lifetime improvement compared to the conventional method which transmits encoded data only after memory is full.

Smooth muscle protein 22-alpha (SM22α) is known as a transformation- and shape change-sensitive actin cross-linking protein found in smooth muscle tissue and fibroblasts; however, its functional role remains uncertain. We reported previously that SM22α overexpression confers resistance against anti-cancer drugs or radiation via induction of metallothionein (MT) isozymes in HepG2 cells. In this study, we demonstrate that SM22α overexpression leads cells to a growth arrest state and promotes cellular senescence caused by treatment with a subclinical dose of γ-radiation (0.05 and 0.1 Gy) or doxorubicin (0.01 and 0.05 μg/ml), compared to control cells. Senescence growth arrest is known to be controlled by p53 phosphorylation/p21(WAF1/Cip1) induction or p16(INK4a)/retinoblastoma protein (pRB) activation. SM22α overexpression in HepG2 cells elevated p16(INK4a) followed by pRB activation, but did not activate the p53/p21(WAF1/Cip1) pathway. Moreover, MT-1G, which is induced by SM22α overexpression, was involved in the activation of the p16(INK4a)/pRB pathway, which led to a growth arrest state and promoted cellular senescence caused by damaging agents. Our findings provide the first demonstration that SM22α modulates cellular senescence caused by damaging agents via regulation of the p16(INK4a)/pRB pathway in HepG2 cells and that these effects of SM22α are partially mediated by MT-1G.

TSPYL5, encoding testis-specific Y-like protein, has been postulated to be a tumor suppressor gene, and its hypermethylation is often associated with human disease, especially cancer. In this study, we report that the TSPYL5 gene was less methylated (30%) in A549 lung adenocarcinoma cells, which are relatively resistant to {gamma}-radiation, than in H460 lung cancer cells, in which the TSPYL5 gene was hypermethylated (95%); thus, the expression level of TSPYL5 is much higher in A549 cells than in H460 cells. We showed that TSPYL5 suppression with silencing RNA in A549 cells up-regulated cellular PTEN, followed by down-regulation of AKT activation. Therefore, blockage of TSPYL5 sensitized A549 cells to cytotoxic agents such as {gamma}-radiation. In addition, TSPYL5 suppression also showed an increased level of p21{sup WAF1/Cip1} and subsequently induced inhibition of cell growth in A549 cells. The overexpression of TSPYL5 in H460 cells showed the opposite effects. This study provides the first demonstration that TSPYL5 modulates cell growth and sensitization of cells to the detrimental effects of damaging agents via regulation of p21{sup WAF1/Cip1} and PTEN/AKT pathway.

In this paper, we propose and demonstrate a transparent and flexible tactile sensor which is designed for multi touch screen application. The sensor module is composed of 2-D array capacitive tactile cells to measure the touch force on multiple positions. The device was fabricated with transparent materials on transparent plastic substrate. The touch input was measured by the capacitance variation resulting from the mechanical deformation of parallel plate capacitor.

Nitric oxide (NO) is involved in many physiological processes and also causes pathological effects by inducing apoptosis. It can enhance or suppress apoptosis depending on its concentration and the cell type involved. In this report, we used cDNA microarray analysis to show that SNAP, an NO donor, strongly induces Bcl-2/adenovirus E1B 19kDa-interacting protein 3 (BNIP3) in macrophages. BNIP3 is a mitochondrial pro-apoptotic protein that contains a Bcl-2 homology 3 domain and a COOH-terminal transmembrane (TM) domain. Macrophages activated by LPS/IFN-gamma produce nitric oxide synthase 2 (NOS2) and release endogenous NO. Expression of BNIP3 was also induced in macrophages by LPS/IFN-gamma, and the induction was blocked by a NOS2 inhibitor, S-methyl-isothiourea. Peritoneal macrophages from NOS2-null mice failed to produce BNIP3 in response to LPS/IFN-gamma. We conclude that BNIP3 expression in macrophages is controlled by the intracellular level of nitric oxide. Overexpression of BNIP3 but not of BNIP3 deltaTM, a BNIP3 mutant without the TM domain and C-terminal tail, led to apoptosis of the cells. Promoter analysis showed that the region between -281 and -1 of the 5'-upstream enhancer region of murine BNIP3 was sufficient for NO-dependent expression of BNIP3.

The CD53 antigen is a member of the tetraspanin membrane protein family that is expressed in the lymphoid-myeloid lineage. Its biological role remains unknown. Using microarrays, we identified CD53 as one of the principal genes up-regulated by exposure of macrophages to LPS. Northern blot analysis confirmed the induction of CD53 in RAW264.7 macrophages treated with LPS or SNAP (a nitric oxide donor). Cells stably transfected with sense CD53 cDNA had increased levels of intracellular GSH and lower levels of peroxide, and were more resistant to H2O2 and to UVB irradiation. Cells harboring antisense CD53 had the opposite properties. We propose that the induction of CD53 is a major mechanism by which macrophages protect themselves against LPS-induced oxidative stress and UVB irradiation.

Smooth muscle protein 22-alpha (SM22alpha) has been postulated to affect the structure and function of the actin filament. In this study, we report on the significant induction of SM22alpha by cytotoxic agents in HepG2 cells. SM22alpha-overexpression inhibited the activation of IGF-1Rbeta/Akt and Erk, consequently suppressing cell proliferation. On the other hand, SM22alpha-overexpressing cells became resistant to apoptotic cell death caused by cytotoxic agents, in which metallothionein (MT) isoforms, especially MT1G, were significantly induced. MT1G-overexpression also conferred cellular resistance, and SM22alpha regulated the expression of MT1G at a transcriptional level. This study provides the first demonstration of SM22alpha-induced blockage of cell proliferation and cellular resistance to overcome the detrimental effects of damaging agents.