• Proceedings of the Korean Nutrition Society Conference
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• 1995.11b
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• pp.11-34
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• 1995

Growth hormone (GH) plays a key role in regulating postnatal growth and can stimulate growth of animals by acting directly on specific receptors on the plasma membrane of tissues or indirectly through stimulating insulin-like growth factor (IGF)-I synthesis and secretion by the liver and other tissues. IGF-I and IGF-Ⅱ are polypeptides with structural similarity with proinsulin that stimulate cell proliferation by endocrine, paracrine and autocrine mechanisms. The initial event in the metabolic action of IGFs on target cells appears to be their binding to specific receptors on the plasma membrane. Current evidence indicates that the mitogenic actions of both IGFs are mediated primarily by binding to the type I IGF receptors, and that IGF action is also mediated by interactions with IGF-binding proteins (IGFBPs). Six distinct IGFBPs have been identified that are characterized by cell-specific interaction, transcriptional and post-translational regulation by many different effectors, and the ability to either potentiate or inhibit IGF actions. Nutritional deficiencies can have their devastating consequence during growth. Although IGF-I is the major mediator of GH's action on somatic growth, nutritional status of an organism is a critical regulator of IGF-I and IGFBPs. Various nutrient deficiencies result in decreased serum IGF-I levels and altered IGFBP levels, but the blood levels of GH are generally unchanged or elevated in malnutrition. Effects of protein, energy, vitamin C and D, and zinc on serum IGF and IGFBP levels and tissue mRNA levels were reviewed in the text. Multiple factors are involved in the regulation of intestinal epithelial cell growth and differentiation. Among these factors the nutritional status of individuals is the most important. The intestinal epithelium is an important site for mitogenic action of the IGFs in vivo, with exogenous IGF-I stimulating mucosal hyperplasia. Therefore, the IGF system appears to provide and important mechanism linking nutrition and the proliferation of intestinal epithelial cells. In order to study the detailed mechanisms by which intestinal mucosa is regulated, we have utilized IEC-6 cells, an intestinal epithelial cell line and Caco-2 cells, a human colon adenocarcinoma cell line. Like intestinal crypt cells analyzed in vivo or freshly isolated intestinal epithelial cells, IEC-6 cells and Caco-2 cells possess abundant quatities of both type Ⅰ and type Ⅱ IGF receptors. Exogenous IGFs stimulate, whereas addition of IGFBP-2 inhibits IEC-6 cell proliferation. To investigate whether endogenously secreted IGFBP-2 inhibit proliferation, IEC-6 cells were transfected with a full-length rat IGFBP-2 cDNA anti-sense expression construct. IEC-6 cells transfected with anti-sense IGFBP-2 protein in medium. These cells grew at a rate faster than the control cells indicating that endogenous IGFBP-2 inhibits proliferation of IEC-6 cells, probably by sequestering IGFs. IEC-6 cells express many characteristics of enterocyte, but do not undergo differentiation. On the other hand, Caco-2 cells undergo a spontaneous enterocyte differentiation. On the other hand, Caco-2 cells undergo a spontaneous enterocyte differentiation after reaching confluency. We have demonstrated that Caco-2 cells produce IGF-Ⅱ, IGFBP-2, IGFBP-3, and an as yet unidentified 31,000 Mr IGFBP, and that both mRNA and peptide secretion of IGFBP-2 and IGFBP-3 increased, but IGFBP-4 mRNA and protein secretion decreased after the cells reached confluency. These changes occurred in parallel to and were coincident with differentiation of the cells, as measured by expression of sucrase-isomaltase. In addition, Caco-2 cell clones forced to overexpress IGFBP-4 by transfection with a rat IGFBP-4 cDNA construct exhibited a significantly slower growth rate under serum-free conditions and had increased expression of sucrase-isomaltase compared with vector control cells. These results indicate that IGFBP-4 inhibits proliferation and stimulates differentiation of Caco-2 cells, probably by inhibiting the mitogenic actions of IGFs.

• Molecules and Cells
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• v.26 no.5
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• pp.443-453
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• 2008

The Bric-a-brac, Tramtrack, Broad-complex (BTB) domain is a protein-protein interaction domain that is found in many zinc finger transcription factors. BTB containing proteins play important roles in a variety of cellular functions including regulation of transcription, regulation of the cytoskeleton, protein ubiquitination, angiogenesis, and apoptosis. Here, we report the cloning and characterization of a novel human gene, KLHL31, from a human embryonic heart cDNA library. The cDNA of KLHL31 is 5743 bp long, encoding a protein product of 634 amino acids containing a BTB domain. The protein is highly conserved across different species. Western blot analysis indicates that the KLHL31 protein is abundantly expressed in both embryonic skeletal and heart tissue. In COS-7 cells, KLHL31 proteins are localized to both the nucleus and the cytoplasm. In primary cultures of nascent mouse cardiomyocytes, the majority of endogenous KLHL31 proteins are localized to the cytoplasm. KLHL31 acts as a transcription repressor when fused to GAL4 DNA-binding domain and deletion analysis indicates that the BTB domain is the main region responsible for this repression. Overexpression of KLHL31 in COS-7 cells inhibits the transcriptional activities of both the TPA-response element (TRE) and serum response element (SRE). KLHL31 also significantly reduces JNK activation leading to decreased phosphorylation and protein levels of the JNK target c-Jun in both COS-7 and Hela cells. These results suggest that KLHL31 protein may act as a new transcriptional repressor in MAPK/JNK signaling pathway to regulate cellular functions.

• Development and Reproduction
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• v.11 no.2
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• pp.111-119
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• 2007

Differentiation of cells can be induced through modulation of endogenous regulators using exogenous factors. Useful transfection systems to transport a specific exogenous regulator into cell have been tried but still there are many obstacles to overcome. In this study, we examined the transfection efficiency of cell permeable peptides (CPPs) in mouse embryonic stem cell under the various conditions. To identify the CPP-mediated translocation of a protein, we employed recombinant CPP-enhanced green fluorescent protein (EGFP). Viability of R1 cells was different between experimental groups depending on the kind of CPP and the concentration of CPP-EGFP. Translocation of CPP-EGFPs into the R1 cells was not detected until 30 min after CPP-EGFPs treatment in all groups. After 1 hr, translocation of pEP-1-EGFP-N was detected, but it could not be detected in the other group. Transfection of pEP-1EGFP-N was independent on its concentration. The time course did not show saturation even after 24 hr in pEP-1-EGFP-N. These results showed that the permeability depended on the kind of CPP and the location of His-tag in the case of examined CPPs, and did not need biological energy. On summary, the efficiency of transfection of CPP-EGFP depends on the CPP sequences but the culture time is not a key factor in transfection for the mouse embryonic stem cell. For the future studies to improve the efficiency of translocation of protein into embryonic stem cells, it is needed to develop modified CPP or mediator. The studies would be very useful to induce the differentiation of embryonic stem cells.

• Journal of Gastric Cancer
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• v.5 no.4 s.20
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• pp.238-245
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• 2005

Purpose: Ghrelin, produced primarily in the gastrointestinal tract, including the stomach, has been reported to reflect nutritional status and to control homeostasis by influencing food intake and adiposity. The purpose of this study is to evaluate nutritional status, as well as plasma and gastric tissue ghrelin levels, in patients with gastric cancer who underwent a gastrectomy. Materials and Methods: Eighty patients were analyzed by the degree of weight loss $(weight\;loss{\geq}5%\;or\;<5%)$ and the extent of gastrectomy (subtotal or total gastrectomy). Blood samples were collected from all patients preoperatively and postoperatively especially at seven days. Gastric tissues, including tumor and normal tissues, were obtained from the resected stomach. levels of plasma and tissue ghrelin were measured with a commercial ELISA kit. Results: There were no significant differences in the clinical characteristics and ghrelin levels of plasma, gastric tumor tissue and normal tissue by the degree of weight loss. The ghrelin levels in plasma and tumor tissue showed no correlations with each other while the ghrelin level in tumor tissue was significantly lower than that in normal tissue. The degree of cellular differentiation also had an association with ghrelin production. A gastrectomy proved to decrease significantly plasma ghrelin levels, body mass index, and biochemical markers, regardless of the extent of gastric resection. Conclusion: These results show that gastric cancer affects the production of ghrelin in the gastric mucosa and that ghrelin is mainly produced in stomach even though it could be partially covered by endogenous ghrelin from other organs following a gastrectomy. However, we should further investigate which other factors have an impact on energy consumption, ghrelin secretion, and changes in ghrelin levels after a gastrectomy.

• Development and Reproduction
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• v.13 no.4
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• pp.207-215
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• 2009

Numerous factors can affect the activities of hypothalamus-pituitary-gonad (HPG) hormonal axis, resulting in alteration of reproductive capacity or status such as onset of puberty and menopause. Soon after the finding of leptin, a multifunctional hormone secreted from adipocytes, a close relationship between reproduction and body energy balance have been manifested. Ghrelin, another multifunctional hormone from gastrointestinal tract, is an endogenous ligand of growth hormone secretagogue receptor (GHSR), and is thought to be a counterpart of leptin in the regulation of energy homeostasis. As expected, ghrelin can also modulate the reproductive capacity through the modulation of activities of HPG axis. This paper summarizes the current knowledge on the discovery, gene structures, tissue distribution and roles of ghrelin and GHSRs in mammalian reproduction in particular modulation of reproductive hormone secretion in HPG axis. Like POMC gene expression in pituitary gland, preproghrelin gene can generate a complex repertoire of transcripts which further undergo alternative splicing and posttranslational modifications. Concerning the roles of preproghrelin gene products in the control of body physiology except energy homeostasis, limited knowledge is available so far. Several lines of evidence, however, show the interplay of ghrelin between metabolism and reproduction. In rat and human, the distribution of ghrelin receptor GHSRs (GHSR1a and GHSR1b) has been confirmed not only in the hypothalamus and pituitary which were originally postulated as target of ghrelin but also in the testis and ovary. Expression of the preproghrelin gene in the brain and gonads was also verified, suggesting the local role (s) of ghrelin in HPG axis. Ghrelin might play a negative modulator in the secretions of hypothalamic GnRH, pituitary gonadotropins and gonadal steroids though the action on pituitary is still questionable. Recent studies suggest the involvement of ghrelin in regulation of puberty onset and possibly of menopause entry. It is now evident that ghrelin is a crucial hormomal component in 'brain-gut' axis, and is a strong candidate links between metabolism and reproduction. Opposite to that for leptin, ghrelin signaling is likely representing the 'hunger' state of body energy balance and is necessary to avoid the energy investment into reproduction which has not a top priority in maintaining homeostasis. Further researches are needed to gain a deep insight into the more precise action mechanism and role of ghrelin in reproduction, and to guarantee the successful biomedical applications.

• Korean Journal of Health Education and Promotion
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• v.23 no.4
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• pp.125-153
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• 2006

This study was intended to describe women's weight controlling by creating a hypothetic model on the weight adjustment behavior and by examining a cause and effect relationship, and to contribute to countermeasures for practicing their promotion of health and improving the quality of life through creating a predictable model. The subject of study was women who utilize the beauty shop located in Seoul, Busan and Daegu and the study period was 12 weeks from July 10 to September 30 in 2004. Gathered 1093 person's general specialty related with weight adjustment and analyzed covariance to prove the hypothesis using statistics compiled from authentic sources. Also proved coincidence of the hypothetical model. Exogenous variables of the hypothetical model are composed of recognition of her body shape, fatness level, age, stress, and self-respect. Endogenous variables are health- control mind, recognized health state, self-efficacy, intention, and behavior of weight adjustment. There were 5 measured variables for exogenous variable(x). There were 8 measured variable(y) for exogenous variable. And coincidence $x^2=297.38$, standard $x^2(x^2/df)=7.08$, GFI=0.962, AGFI=0.917, NFI=0.875, TLI=0.794, CFI=0.889, RMSEA=0.075. The result of hypothesis had an epoch-making record that 20 out of 27 hypothesis was proved positive way. Generally weight adjustment has been highly seen in housewives, the married and the old age. Health control mind seems to be high as fatness level, age, and self-respect are high and low stress. Recognized health state is high as age and self-respect are high and low stress. However, it is not much related with recognition of her body shape and fatness level. If age, self-respect, health control mind, recognized health state and self-efficacy are high intention of behavior is also high, but intention of behavior has no relation with recognition of her body shape, fatness level and stress. If fatness level, age, self-respect, health control mind, recognized health state and self-efficacy and intention of behavior are high, execution of weight adjustment will be high. However, recognized health state and stress has no influence for weight adjustment. To increase the coincidence of hypothesis and take a simple model I modified a model and then I got the coincidence $x^2=215.62$, standard $x^2(x^2/df)=6.34$, GFI=0.970, AGFI=0.931, NFI=0.902, TLI=0.901, CFI=0.915, RMSEA=0.070. This result is a bit better than original hypothetical model's so that this model might be more suitable. In this modification model, the factors of weight adjustment seems to be high according to this order self-efficacy, recognized health state, age, intention, health control mind, self-respect, fatness level and stress. With this result I suggest ; 1. Enforcement of IR that everybody can be controlled weight adjustment herself and continuous education, which is related with regular habit (food, exercise, restriction of a favorite food and behavior training etc.) is also needed. 2. Because self-efficacy is influenced to execution of weight adjustment specific program which can increase self-efficacy should have to develop and we need to utilize it to take care of herself. 3. To protect fatness and be active weight adjustment the peculiar program including the concept of self-respect, recognized health state, health control mind and intention must be developed and not only women but also all of people should be educated. 4. This hypothetical model is forecasting women's weight adjustment behavior and can be utilized for fundamental data to increase those people's health.

• Sleep Medicine and Psychophysiology
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• v.4 no.1
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• pp.57-65
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• 1997

As jet lag of modern travel continues to spread, there has been an exponential growth in popular explanations of jet lag and recommendations for curing it. Some of this attention are misdirected, and many of those suggested solutions are misinformed. The author reviewed the basic science of jet lag and its practical outcome. The jet lag symptoms stemed from several factors, including high-altitude flying, lag effect, and sleep loss before departure and on the aircraft, especially during night flight. Jet lag has three major components; including external de synchronization, internal desynchronization, and sleep loss. Although external de synchronization is the major culprit, it is not at all uncommon for travelers to experience difficulty falling asleep or remaining asleep because of gastrointestinal distress, uncooperative bladders, or nagging headaches. Such unwanted intrusions most likely to reflect the general influence of internal desynchronization. From the free-running subjects, the data has revealed that sleep tendency, sleepiness, the spontaneous duration of sleep, and REM sleep propensity, each varied markedly with the endogenous circadian phase of the temperature cycle, despite the facts that the average period of the sleep-wake cycle is different from that of the temperature cycle under these conditions. However, whereas the first ocurrence of slow wave sleep is usually associated with a fall in temperature, the amount of SWS is determined primarily by the length of prior wakefulness and not by circadian phase. Another factor to be considered for flight in either direction is the amount of prior sleep loss or time awake. An increase in sleep loss or time awake would be expected to reduce initial sleep latency and enhance the amount of SWS. By combining what we now know about the circadian characteristics of sleep and homeostatic process, many of the diverse findings about sleep after transmeridian flight can be explained. The severity of jet lag is directly related to two major variables that determine the reaction of the circadian system to any transmeridian flight, eg., the direction of flight, and the number of time zones crossed. Remaining factor is individual differences in resynchmization. After a long flight, the circadian timing system and homeostatic process can combine with each other to produce a considerable reduction in well-being. The author suggested that by being exposed to local zeit-gebers and by being awake sufficient to get sleep until the night, sleep improves rapidly with resynchronization following time zone change.