• BMB Reports
• /
• v.32 no.2
• /
• pp.103-111
• /
• 1999

Hh proteins represent a new signaling paradigm in metazoan development. In species ranging from fruit flies to humans, Hh proteins mediate multiple processes vital to appropriate pattern formation in the developing embryo. Hh proteins undergo an autoprocessing event in which the full-length protein is cleaved into N-terminal and C-terminal domains (Hh-N and Hh-C, respectively), and a cholesterol moiety becomes covalently attached to Hh-N. All known signaling activities of Hh proteins are mediated by Hh-N while both the cleavage and cholesterol transfer reactions are mediated by Hh-C. The cholesterol attached to Hh-N is required to retrict the range of Hh signaling and may be involved in ensuring appropriate reception of the Hh signal in target tissues. Disruptions of Hh signaling pathways lead to severe developmental defects in newborns and cancers in adults. While studies of Hh proteins have yielded a wealth of new insight into the molecular mechanisms of metazoan development, many outstanding questions concerning Hh signaling mechanisms ensure that unraveling the secrets of this molecule will keep scientists well entertained for the foreseeable future.

• IMMUNE NETWORK
• /
• v.11 no.6
• /
• pp.336-341
• /
• 2011

T cell receptor (TCR) signaling plays a critical role in T cell development, survival and differentiation. In the thymus, quantitative and/or qualitative differences in TCR signaling determine the fate of developing thymocytes and lead to positive and negative selection. Recently, it has been suggested that self-reactive T cells, escape from negative selection, should be suppressed in the periphery by regulatory T cells (Tregs) expressing Foxp3 transcription factor. Foxp3 is a master factor that is critical for not only development and survival but also suppressive activity of Treg. However, signals that determine Treg fate are not completely understood. The availability of mutant mice which harbor mutations in TCR signaling mediators will certainly allow to delineate signaling events that control intrathymic (natural) Treg (nTreg) development. Thus, we summarize the recent progress on the role of TCR signaling cascade components in nTreg development from the studies with murine model.

• BMB Reports
• /
• v.56 no.2
• /
• pp.56-64
• /
• 2023

Nitrogen (N) is an essential macronutrient required for plant growth and crop production. However, N in soil is usually insufficient for plant growth. Thus, chemical N fertilizer has been extensively used to increase crop production. Due to negative effects of N rich fertilizer on the environment, improving N usage has been a major issue in the field of plant science to achieve sustainable production of crops. For that reason, many efforts have been made to elucidate how plants regulate N uptake and utilization according to their surrounding habitat over the last 30 years. Here, we provide recent advances focusing on regulation of N uptake, allocation of N by N transporting system, and signaling pathway controlling N responses in plants.

• The Korean Journal of Physiology and Pharmacology
• /
• v.19 no.1
• /
• pp.51-57
• /
• 2015

The etiology of periodontal disease is multifactorial. Exogenous stimuli such as bacterial pathogens can interact with toll-like receptors to activate intracellular calcium signaling in gingival epithelium and other tissues. The triggering of calcium signaling induces the secretion of pro-inflammatory cytokines such as interleukin-8 as part of the inflammatory response; however, the exact mechanism of calcium signaling induced by bacterial toxins when gingival epithelial cells are exposed to pathogens is unclear. Here, we investigate calcium signaling induced by bacteria and expression of inflammatory cytokines in human gingival epithelial cells. We found that peptidoglycan, a constituent of grampositive bacteria and an agonist of toll-like receptor 2, increases intracellular calcium in a concentration-dependent manner. Peptidoglycan-induced calcium signaling was abolished by treatment with blockers of phospholipase C (U73122), inositol 1,4,5-trisphosphate receptors, indicating the release of calcium from intracellular calcium stores. Peptidoglycan-mediated interleukin-8 expression was blocked by U73122 and 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetrakis (acetoxymethyl ester). Moreover, interleukin-8 expression was induced by thapsigargin, a selective inhibitor of the sarco/endoplasmic reticulum calcium ATPase, when thapsigargin was treated alone or co-treated with peptidoglycan. These results suggest that the gram-positive bacterial toxin peptidoglycan induces calcium signaling via the phospholipase C/inositol 1,4,5-trisphosphate pathway, and that increased interleukin-8 expression is mediated by intracellular calcium levels in human gingival epithelial cells.

• Toxicological Research
• /
• v.24 no.2
• /
• pp.93-100
• /
• 2008

Targeting protein kinases has been active area in drug discovery. The c-Jun N-terminal kinases(JNKs) have also been target for development of novel therapy in various diseases, since the roles of JNK signaling in pathological conditions were revealed in studies using jnk-deficient mice. Small molecule inhibitors and peptide inhibitors are identified for therapeutic intervention of JNK signaling pathway. SP-600125, an anthrapyrazole small molecule inhibitor for JNK with high potency and selectivity has been widely used for dissecting JNK signaling pathway. CC-401 is the first JNK inhibitor that went into clinical trial for inflammation and leukemia. Inhibitor for mixed lineage kinase (MLK), CEP-1347 also negatively regulates JNK signaling, and tried for potential use in Parkinson's disease. Cell-permeable peptide inhibitor D-JNKI-1 is being developed for the treatment of hearing loss. The current status of these JNK inhibitors and safety issue is discussed in the minireview.

• Journal of the Korean Society for Railway
• /
• v.15 no.1
• /
• pp.42-47
• /
• 2012

There are ATC (Automatic Train Control), ATP (Automatic Train Protection), ATS (Automatic Train Stop) and ATO (Automatic Train Operation) etc. in train control systems. As various train control systems are installed according to sections, on-board signaling systems are installed to apply to the section. Hence, operation flexibility of trains is decreased. In other words, when trains are operated in the section where other train control systems are used, the on-board signaling systems are changed. Recently, a study on the combined on-board signaling system has been researched to solve this problem. The combined on-board signaling system consists of ATC, ATP and ATS device. Because the train control systems are vital, it needs to design the combined on-board signaling system by using k out of n system. In this paper, when k out of n system is applied in the combined on-board signaling system, the reliability and loss cost are analyzed by using failure rate in each device. Hence, the ideal number of systems is presented according to the number of outputs.

• The Korean Journal of Pain
• /
• v.34 no.4
• /
• pp.405-416
• /
• 2021

Background: This study investigated the effect of intrathecal Sec-O-glucosylhamaudol (SOG) on the p38/c-Jun N-terminal kinase (JNK) signaling pathways, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)-related inflammatory responses, and autophagy in a spinal nerve ligation (SNL)-induced neuropathic pain model. Methods: The continuous administration of intrathecal SOG via an osmotic pump was performed on male Sprague-Dawley rats (n = 50) with SNL-induced neuropathic pain. Rats were randomized into four groups after the 7th day following SNL and treated for 2 weeks as follows (each n = 10): Group S, sham-operated; Group D, 70% dimethylsulfoxide; Group SOG96, SOG at 96 ㎍/day; and Group SOG192, SOG at 192 ㎍/day. The paw withdrawal threshold (PWT) test was performed to assess neuropathic pain. Western blotting of the spinal cord (L5) was performed to measure changes in the expression of signaling pathway components, cytokines, and autophagy. Additional studies with naloxone challenge (n = 10) and cells were carried out to evaluate the potential mechanisms underlying the effects of SOG. Results: Continuous intrathecal SOG administration increased the PWT with p38/JNK mitogen-activated protein kinase (MAPK) pathway and NF-κB signaling pathway inhibition, which induced a reduction in proinflammatory cytokines with the concomitant downregulation of autophagy. Conclusions: SOG alleviates mechanical allodynia, and its mechanism is thought to be related to the regulation of p38/JNK MAPK and NF-κB signaling pathways, associated with autophagy during neuroinflammatory processes after SNL.

• BMB Reports
• /
• v.44 no.12
• /
• pp.772-781
• /
• 2011

Branched N-glycans are produced by a series of glycosyltransferases including N-acetylglucosaminyltransferases and fucosyltransferases and their corresponding genes. Glycans on specific glycoproteins, which are attached via the action of glycosyltransferases, play key roles in cell adhesion and signaling. Examples of this are adhesion molecules or signaling molecules such as integrin and E-cadherin, as well as membrane receptors such as the EGF and TGF-${\beta}$ receptors. These molecules also play pivotal roles in the underlying mechanism of a variety of disease such as cancer metastasis, diabetes, and chronic obstructive pulmonary disease (COPD). Alterations in the structures of branched N-glycans are also hall marks and are useful for cancer biomarkers and therapeutics against cancer. This mini-review describes some of our recent studies on a functional glycomics approach to the study of branched N-glycans produced by N-acetylglucosaminyltransferases III, IV, V and IX (Vb) (GnT-III, GnT-IV, V and IX (Vb)) and fucosyltransferase 8 (Fut8) and their pathophysiological significance, with emphasis on the importance of a systems glycobiology approach as a future perspective for glycobiology.

• Nutrition Research and Practice
• /
• v.6 no.6
• /
• pp.513-519
• /
• 2012

Aged garlic extract (AGE) is known to have a protective effect against immune system, endothelial function, oxidative stress and inflammation. We examined the effects of exercise with and without aged garlic extract administration on body weight, lipid profiles, inflammatory cytokines, and oxidative stress marker in high-fat diet (HFD)-induced obese rats. Forty-five Sprague-Dawley rats were fed either a HFD (HFD, n = 40) or a normal diet (ND, n = 5) for 6 weeks and thereafter randomized into ND (n = 5), HFD (n = 10), HFD with AGE (n = 10), HFD with Exercise (n = 10), or HFD with Exercise+AGE (n = 10) for 4 weeks. AGE groups were administered at a dose of 2.86 g/kg body weight, orally. Exercise consisted of running 15-60 min 5 days/week with gradually increasing intensity. AGE (P<0.01), Exercise, and Exercise+AGE (P<0.001) attenuated body weight gain and food efficiency ratio compared to HFD. Visceral fat and liver weight gain were attenuated (P<0.05) with all three interventions with a greater effect on visceral fat in the Exercise+AGE than AGE (P<0.001). In reducing visceral fat (P<0.001), epididymal fat (P<0.01) and liver weight (P<0.001), Exercise+AGE was effective, but exercise showed a stronger suppressive effect than AGE. Exercise+AGE showed further additive effects on reducing visceral fat and liver weight (P<0.001). AGE significantly attenuated the increase in total cholesterol and low-density lipoprotein-cholesterol compared with HFD (P<0.05). Exercise+AGE attenuated the increase in triglycerides compared with HFD (P<0.05). Exercise group significantly decrease in C-reactive protein (P<0.001). These results suggest that AGE supplementation and exercise alone have anti-obesity, cholesterol lowering, and anti-inflammatory effects, but the combined intervention is more effective in reducing weight gain and triglycerides levels than either intervention alone.

• The Journal of Korean Institute of Communications and Information Sciences
• /
• v.23 no.5
• /
• pp.1397-1408
• /
• 1998

Service networks for the future communication networks will be combined by the B-ISDN networks. These service networks also will use SS No.7 as the signaling transport network for the control of user requriement service. Therefore, ITU-T recommended B-ISDN signaling layers for SS No.7 as a substitute for N-ISDN MTP signaling layer. In this paper, we propose the implementation structure and describe the characteristics and functions of each signaling layer of SS No.7, which are adapted to ATM switching system, and evaluate a performance. The structure of SSCOP transmission buffer using a linked list and an unit frame length is proposed for SAAL layer and the implementation structure and internal routing method according to the ATM switching system are also proposed for MTP-3b layer. Additionally, we propose the ISUP/B-ISUP level interworking structure using only associated mode, which are presented in the first stage of B-ISDN as the effective internatworking structure of SS No.7 for the circuit related signaling network between the existing N-ISDN networks and B-ISDN networks.