• Title/Summary/Keyword: Molecular mechanism

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Comparison study of dermal cell toxicity and zebrafish brain toxicity by humidifier sterilizer chemicals (PHMG, PGH, CMIT/MIT) (가습기 살균제 성분(PHMG, PGH, CMIT/MIT)의 사람 피부세포 독성 및 제브라피쉬 뇌신경 독성 비교 연구)

  • Cho, Kyung-Hyun;Kim, Jae-Ryong
    • Korean Journal of Environmental Biology
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    • v.38 no.2
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    • pp.271-277
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    • 2020
  • Toxicities to many organs caused by humidifier disinfectants have been reported. Recently, humidifier disinfectants have been reported to cause cardiovascular, embryonic, and hepatic toxicities. This study was designed to investigate the toxic mechanism of humidifier disinfectants and compare toxicity in a cellular model and a zebrafish animal model. Because brain toxicity and skin toxicity have been less studied than other organs, we evaluated toxicity in a human dermal cell line and zebrafish under various concentrations of humidifier disinfectants that included polyhexamethyleneguanidine phosphate (PHMG), oligo-[2-(2-ethoxy)-ethoxyethyl-guanidinium-chloride] (PGH) and methylchloroisothiazolinone/methylisothiazolinone (CMIT/MIT). A human dermal fibroblast cell line was treated with disinfectants (0, 2, 4, 6, 8, and 16 mg L-1) to compare their cytotoxicity. The fewest PHMG-treated cells survived (up to 33%), while 49% and 40% of the PGH- and CMIT/MIT-treated cells, respectively, survived. The quantification of oxidized species in the media revealed that the PHMG-treated cells had the highest MDA content of around 28 nM, while the PGH- and CMIT/MIT-treated cells had 13 and 21 nM MDA, respectively. As for brain toxicity, treatment of the zebrafish tank water with CMIT/MIT (final 40 mg L-1) for 30 min resulted in a 17-fold higher production of reactive oxygen species (ROS) than in the control. Treatment with PGH or PHMG (final 40 mg L-1) resulted in 15- and 11-fold higher production, respectively. The humidifier disinfectants (PHMG, PGH, and CMIT/MIT) showed severe dermal cell toxicity and brain toxicity. These toxicities may be relevant factors in understanding why some children have language disorders, motor delays, and developmental delays from exposure to humidifier disinfectants.

THE EFFECT OF ALTERED FUNCTIONAL FORCE ON THE EXPRESSION OF SPECIFIC MRNAS IN THE DEVELOPING MOUSE MANDIBLE (하악골의 발육중인 생쥐에서 기능력의 변화가 특이-유전자 발현에 미치는 영향)

  • Kim, Hyung-Tae;Park, Joo-Cheol;Lee, Chang-Seop;Park, Heon-Dong
    • Journal of the korean academy of Pediatric Dentistry
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    • v.30 no.2
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    • pp.308-319
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    • 2003
  • Mechanical forces are known to have an effect on bone formation, maintenance and remodeling, and there is evidence that the development of the mandibular condyle in the rat or mouse is influenced by altered functional force. However, studies are lacking in molecular-biologic mechanism such as the identification of differentiation factor induced from functional force. Here a mouse model was used to investigate the functional stress-responsive gene or factors which is related to the altered force by comparing the expression genes of functional state and hypo-functional state of the mouse mandible. ICR mice were provisioned with either a soft, mushy diet (soft-diet group) or hard rat pellets (hard-diet group) beginning at weaning for the alteration of functional force and subsequently sacrificed at 89 days of age. Incisor of mice in group 1 were trimmed twice a week to reduce occlusal forces. After killing the animals, mandibular bone including condyle were collected for RNA extraction, subtractive hybridization, northern blot analysis and mRNA in-situ hybridization. The results as follows; 1. A total of 39 clones were sequenced, and 11 individual sequence types were subsequently identified by subtractive hybridization, as 28 clones were represented twice in the analyzed sets. 2. Consequently four candidate clones, FS-s (functional stress-specific)2, -5, -18, and -22 were identified and characterized by homolgy search and northern analysis. Four of these clones, FS-s2, -5, -18, and -22, were shown to be expressed differentially in the hard-diet group. 3. Histologic sections showed that osteoblastic activity along the bone trabeculae and active bone remodeling were significantly lower in soft than in hard diet animals. A soft diet seems to enable a longer period of endochondral ossification in the mandibular condyle. 4. Although the mRNAs of FS-s2, -5, -18, and -22 were expressed rarely by cells of the soft-diet group, highest expression was detected in the cells of the hard-diet group. Together with the above results, it is suggested that FS-s2, -5, -18, and -22 could act as an important factors controlling the tissue changes in response to functional stress. The exact functional significance of these findings remains to be established.

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Laboratory-scale fruiting body formation of Pleurotus ostreatus using the petri dish culture (느타리의 기내 자실체 형성 및 그 유도조건에 관한 연구)

  • Joh, Joong-Ho;Chu, Kyo-Sun;Kim, Beom-Gi;Kong, Won-Sik;Yoo, Young-Bok;Lee, Seung-Jae;Cho, Bong-Gum;Lee, Chang-Soo
    • Journal of Mushroom
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    • v.2 no.1
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    • pp.15-20
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    • 2004
  • Pleurotus ostreatus, the oyster mushroom, is one of the most widely cultivated and important edible mushrooms in the world. In order to study the developmental process of P. ostreatus and its regulatory mechanism, a new culturing method needs to be established for inducing the fruiting body and sporulation in the laboratory. In this study, we have examined whether the fruiting body of P. ostreatus can be formed on the plastic petri dish which are commonly used for cell culture in the laboratory. The strain was cultured on $60{\times}15mm$ plastic petri dish with potato dextrose agar media at $28^{\circ}C$ for mycelial growth and then at $18^{\circ}C$ for the formation of primordia and fruiting bodies within plant growth chamber. The development of primordia into fruiting bodies was achieved on cultured dishes under air ventilation. At the primordia stage, the normal formation of fruiting body was blocked by sealing the plastic dish with parafilm. The periods requiring for the formation of primordia and fruiting bodies were examined on the dish culture. About 96% and 76% of cultured samples formed primordia and fruiting bodies under the optimal conditions during ten weeks of culture, respectively. These culturing periods, however, were changed by the mechanical injury treatment to mycelia. As other factors affecting the fruiting body formation, the effects of light and cold shock have been tested. No fruiting formation was observed on the cultured dishes under the dark. The cold shock treatment by storing cultured dishes for one day at $4^{\circ}C$ did not have any significant effects in the fruiting body formation. Spores of fruiting bodies acquired from the petri dishes could be germinated on culture media at $28^{\circ}C$. These results suggest that the fruiting bodies of P. ostreatus can be formed on the experimental petri dish and this dish-culturing method is useful for understanding of the developmental process of P. ostreatus in the laboratory. Furthermore, the dish-culturing method is able to shorten the life cycle of P. ostreatus without requiring large area and expensive device.

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Effects of Platycodin D on Gene Expressions of Pro-adipogenic and Anti-adipogenic Regulators in 3T3-L1 Cells (3T3-L1 세포에서 지방세포형성 유도조절자 및 억제조절자의 발현에 대한 platycodin D의 효과)

  • Lee, Hae-Yong;Kang, Ryun-Hwa;Cho, Soo-Hyun;Kim, Sung-Su;Kim, Yeong-Shik;Yoon, Yoo-Sik
    • Journal of Life Science
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    • v.19 no.12
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    • pp.1802-1807
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    • 2009
  • Platycodin D, a major component of Platycodi radix, is known to have various activities including anti-inflammatory, anti-hyperlipidemic, anti-tumor activities and others. Recently, it was reported that platycodin D inhibits fat accumulation and adipogenesis. The aim of this study was to investigate whether various adipogenic regulators are modulated by platycodin D treatment during the adipogenesis of 3T3-L1 cells. mRNA levels of terminal markers of adipogenesis such as ADIPOQ (adiponectin) and GLUT (glucose transporter) 4, which were quantified by real time PCR, were decreased by platycodin D treatment. mRNA expression of PPAR (peroxisome proliferator-activated receptor) $\gamma$ and C/EBP (CCAAT/enhaner binding protein) $\alpha$, which are central transcription factors of adipogenesis, were also decreased by platycodin D treatment. To elucidate the detailed molecular mechanism of platycodin D-induced inhibition of adipogenesis, we analyzed mRNA expression of upstream regulators of PPAR$\gamma$ and C/EPB$\alpha$. mRNA levels of the pro-adipogenic regulators, KROX20 and KLF (Kruppel-like factor) 15 were markedly down-regulated by platycodin D treatment. On the other hand, mRNA expression of CHOP (C/EBP homologous protein), an anti-adipogenic regulator, was significantly up-regulated by platycodin D treatment. mRNA levels of other pro-adipogenic regulators, C/EBP$\beta$ and C/EPB$\delta$, were not affected by platycodin D treatment, and another anti-adipogenic regulator, C/EBP$\gamma$ was also not affected by platycodin D treatment. Taken together, these results suggest that platycodin D-induced inhibition of adipogenesis is mediated by gene interactions including the down-regulation of pro-adipogenic regulators, KROX20 and KLF15, and the up-regulation of an anti-adipogenic regulator, CHOP.

Attenuation of Experimental Autoimmune Hepatitis in Mice with Bone Mesenchymal Stem Cell-Derived Exosomes Carrying MicroRNA-223-3p

  • Lu, Feng-Bin;Chen, Da-Zhi;Chen, Lu;Hu, En-De;Wu, Jin-Lu;Li, Hui;Gong, Yue-Wen;Lin, Zhuo;Wang, Xiao-Dong;Li, Ji;Jin, Xiao-Ya;Xu, Lan-Man;Chen, Yong-Ping
    • Molecules and Cells
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    • v.42 no.12
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    • pp.906-918
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    • 2019
  • MicroRNA-223-3p (miR-223-3p) is one of the potential microRNAs that have been shown to alleviate inflammatory responses in pre-clinical investigations and is highly encased in exosomes derived from bone mesenchymal stem cells (MSC-exosomes). MSC-exosomes are able to function as carriers to deliver microRNAs into cells. Autoimmune hepatitis is one of the challenging liver diseases with no effective treatment other than steroid hormones. Here, we examined whether MSC-exosomes can transfer miR-223-3p to treat autoimmune hepatitis in an experimental model. We found that MSC-exosomes were successfully incorporated with miR-223-3p and delivered miR-223-3p into macrophages. Moreover, there was no toxic effect of exosomes on the macrophages. Furthermore, treatments of either exosomes or exosomes with miR-223-3p successfully attenuated inflammatory responses in the liver of autoimmune hepatitis and inflammatory cytokine release in both the liver and macrophages. The mechanism may be related to the regulation of miR-223-3p level and STAT3 expression in the liver and macrophages. These results suggest that MSC-exosomes can be used to deliver miR-223-3p for the treatment of autoimmune hepatitis.

Evaluation of Toxicological Data on Food Additives and Guideline for ADI establishment - Polydimethylsiloxane as emulsifier - (식품첨가물의 독성자료 고찰과 ADI 평가지침 - 소포제 Polydimethylsiloxane를 사례로 -)

  • Choi, Chan-Woong;Jeong, Ji-Yoon;Park, Hyoung-Su;Moon, Jin-Hyun;Lee, Kwang-Ho;Lee, Hyo-Min
    • Journal of Food Hygiene and Safety
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    • v.24 no.4
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    • pp.352-356
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    • 2009
  • The purpose of this study was to introduce the toxicological study review to evaluate the safety of PDMS on the 69th JECFA meeting. Polydimethylsiloxane is a polymer and its ADI was established at 23rd JECFA meeting in 1979. The ADI was maintained although the specification was expanded at its 26th, 29 th, 37 th meetings. Recently, it was reported that PDMS with low molecular weight and viscosity has high absorption rate and different toxicity, so it was submitted at 69th meeting. Toxicological studies of PDMS were submitted from the sponsor and additional information is collected from a document searching. The toxicological studies were reviewed in accordance with the 'Guidelines for the preparation of toxicological working papers for the Joint FAO/WHO Expert Committee on Food Additives'. In the available acute, sub-chronic and chronic toxicity studies on PDMS, dose-related increases in incidence and severity of ocular lesions(corneal crystal, inflammation of the corneal epithelium etc.) were consistently observed after oral dosing. It seems to be a local irritant effect, but the mechanism by which the ocular lesions arose is unclear, although the lack of absorption of PDMS indicates that it is unlikely to be a direct systemic effect. Consequently, the relevance of the ocular lesions for food use of PDMS could not be determined. The ADI of PDMS was re-established from 0-1.5 mg/kg bw/day to 0-0.8 mg/kg bw/day by applying additional safety factor 2 based on its ocular toxicity. The result of 0-0.8 mg/kg bw/day is a temporary ADI until further data are provided to 2010.

The Mechanism of Iron Transport after Intratracheal Instillation of Iron in Rats (랏트의 기관내 Fe 노출후 Fe 이동에 대한 연구)

  • Kwon, Min;Choi, Byung-Sun;Park, Eon-Sub;Chung, Nam-Hyun;Park, Sung-Jo;Lim, Young;Park, Jung-Duck
    • Journal of Preventive Medicine and Public Health
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    • v.37 no.4
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    • pp.329-336
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    • 2004
  • Objectives : Iron (Fe) is an essential element in biological processes; however excessive Fe is harmful to human health. Some air pollutants contain a high level of Fe, and the human lung could therefore be over-exposed to Fe through inhaled air pollutants. This study was performed to investigate the role of metal transporters (divalent metal transporter 1, DMT1, and metal transporter protein 1, MTP1) in the lung under the environments of Fe deficiency in the body and Fe over-exposure in the lung. Methods : Rats were fed Fe deficient (FeD, 2-6 mg Fe/kg) or Fe supplemented (FeS, 120 mg Fe/kg) diet for 4 weeks, followed by a single intratracheal instillation of ferrous sulfate at low (10 mg/kg) or high (20 mg/kg) dose. Fe concentration was analyzed in the serum, lung and liver, and histopathological findings were observed in the lung at 24 hours after Fe administration. The level of DMT1 and MTP1 expression in the lung was analyzed by RT-PCR. Also, the effect of Fe deficiency in the body was evaluated on the level of Fe concentration and metal transporters compared to FeS-diet fed rats at the end of 4-week FeD or FeS diet. Results : The 4-week FeD diet in rats induced an Fe deficiency anemia with decreased serum total Fe, increased unsaturated Fe binding capacity and hypochromic microcytic red blood cells. The concentration of Fe in the lung and liver was lower in the FeD-diet fed rats than in the FeS-diet fed rats. The level of metal transporters mRNA expression was higher in the FeD-diet fed rats than in the FeS-diet. The concentration of Fe in the lung was increased in a dose-dependent pattern after intratracheal instillation of Fe into the rats, while the level of Fe in the serum and liver was not increased in the low-dose Fe administered rats. Therefore, DMT1 and MTP1 mRNA was highly expressed in both FeD-diet and FeS-diet fed rats, after intratracheal instillation of Fe. Conclusions : DMT1 and MTP1 mRNA were more highly expressed in FeD-diet fed rats than in FeS-diet fed rats. The over-exposure of Fe intratracheally induced high expression of metal transporters and increased Fe deposition in the lung in both FeD-diet and FeS-diet fed rats, but did not increase the Fe level of the serum and liver in low-dose Fe administered rats. These results suggest that the role of metal transporters in the lung might be different in a part from the duodenum under the environment of over-exposure to Fe.

Effects of vitamin C as antioxidant on recovery of left ventricular function after ischemia and reperfusion in isolated rat heart (항산화제로서 비타민 C가 적출된 쥐심장에서 허혈 및 재관류후 좌심실 기능회복에 미치는 영향)

  • 류한영;이철주
    • Journal of Chest Surgery
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    • v.29 no.6
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    • pp.593-598
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    • 1996
  • The large number of past investigation on extended myocardial protection clearly indicates that cold potassium cardioplegia and topical cooling have limited capabilities. Accordingly, more recent experimen- tal approaches have focused on the modalities of reperfusion and their implication on postischemic myo- cardial recovery. Oxygen may play a crucial role in the development of ischemic and reperfusion injury. Reactive oxygen radicals may be produced during ischemia or reperfusion after incomplete reduction of molecular oxygen or from other pathway and then induce fatal injury of the heart. The important obser- vation of oxygen-induced myocardial damage during reperfusion has led to the concept of applying oxy- gen free radical scavengers. So, this study is on dietary vitamin C supplementation as antioxidant in rats to determine whether or not they have a higher tolerance against cardiac ischemia-reperf'usion injury under Langendorff system. Male or female Sprague-Dawley rats (190-33Og) were randomly separated into two groups. Group A was not treated(n=10). Group B received vitamin C supplement (n=10). Experiment was performed 24 hours after vitamin C 200mg fed orally as injectable ascorbic acid. There were significant differences in contractile parameters between control and vitamin C-treated group. The RLVP (r te of post/preischemic left ventricular pressure) and Rdp/dt (rate of post/preischemic dp/dt) were significant statistically between two groups (p<0.05). But, RHR (rate of post/preischemic heart rate), time to first beat and sta'utilization were not significant. In conclusion, pretreatment with the antioxidant, ascorbic acid, was found to preserve left ventricular contractile function. But the precise mechanism of action of ascorbic acid has not as yet been determined, so further study will be required.

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Effect of Epidural Morphine and Bupivacaine with Hypertonic Solution or the Duration of Analgesia (경막외 Morphine, Bupivacaine 및 고장성용액 혼주시 진통지속효과에 미치는 영향)

  • Park, Wook;Park, Kwang-Won
    • The Korean Journal of Pain
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    • v.1 no.1
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    • pp.64-73
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    • 1988
  • Recent studios have shown that narcotic drags produce an unusually intense, prolonged and segmental analgesic action in man whoa injected into the spinal subarachnoid or epidural space (Wang et al, 1979; Behar et al, 1979; Cousins et al, 1979; Magora et a., 1980, Johnston and McCaughey, 1980). Since 1960, many investigators claimed that low molecular weight(LMW) dextran increased the clinical duration of lidocaine(Loder, 1960; Loder, 1962), tetracaine (Chinn and Wirjoatmadja, 1967) and bupivacaine(Kaplan et al, 1975) in man but the mechanism of the action of dextran was unclear. But Curtiss and Scurlock(1979), and Buckled and Fink(1979) claimed that LMW dextran has no effect on the duration of action of bupivacaine in animal studies. The present study was performed to evaluate the clinical efficacy of analgesia by the thoracic epidural injection of morphine and bupivacaine mixture for the relief of pain due to fractured or contused ribs, to evaluate the duration of analgesic effect by the use of the above mixture in a hypertonic solution(dextran 70 or 50% dextrose in water) and to observe the possibility of improvement in the lung function after the pain block. The complications following the pain block were also observed. The 50 single thoracic epidural injections of the mixture were divided into three groups : Group 1(n=15) served as a control group and drags used for the relief of pain were as follows(Mean$\pm$S.D.): morphine($2.13{\pm}1.64\;mg$), 0.5% bupivacaine($3.10{\pm}1.04\;ml$) and 0.9% saline($3.64{\pm}1.11\;ml$). Group 2(n=16) serves as an experimental group and drugs were as follows(Mean$\pm$S.D.): morphine($2.13{\pm}0.72\;mg$), 0.5% bupivacaine($3.06{\pm}0.77\;ml$) and dextran 70($3.75{\pm}1.29\;ml$). Group 3 (n=19) served as an experimental group and drags were as follows(Mean$\pm$S.D.) : morphine($2.42{\pm}0.51\;mg$), 0.5% bupivacaine($3.21{\pm}0.71\;ml$) and 50% dextrose in water($3.58{\pm}1.11\;ml$). The results are were follows: 1) The Dumber of patients who obtained excellent and good analgesic effects following the block were greater in the experimental Croup 2(94%) and Group 3 (90%) than theme of the control Group 1 (80%). 2) The duration of pain relief which lasted more than 3 days after the epidural block was longer in the experimental Group 2 (81%) and Group 3 (75%) than those of the control Croup 1(67%). 3) The pulmonary reserve(FVC%+FEV 1.0%) of 27 cases who were treated by the pain block between 1 and 31 drys following the chest injury was increased to about 13% than those before the block, and that of 13 cases between 32 and 82 days following the chest injury was decreased to about 4% than those before the block. 4) Of the complications following the pain block, there were 5 cased(10%) of nausea within 2 hours following the block, 4 cases(8%) of vomiting after 2 hours following the block, 10 cases(20%) of pruritus after 3~4 hours following the block, 17 cases(34%) of transient urinary retention which tasted 8 to 19 hours, 3 cases(6%) of headache within 2 hoers following the block and 2 cases(4%) of dural puncture. In conclusion, it is suggested that the clinical duration of analgesic effect produced by morphine and bupivacaine mixture can be prolonged by addition of the hypertonic solution to the mixture.

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Effects of the Applications of Clay Minerals on the Early Growth of Red Pepper in Growing Medium (점토광물 처리에 따른 상토에서 고추의 초기생장 효과)

  • Lee, Dong-Gi;Lee, Seok-Eon;Kim, Deok-Hyun;Hong, Hyeon-Ki;Nam, Ju-Hyun;Choi, Jong-Soon;Lee, Moon-Soon;Woo, Sun-Hee;Chung, Keun-Yook
    • Horticultural Science & Technology
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    • v.30 no.4
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    • pp.463-470
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    • 2012
  • As the advanced seeding technology through use of plug tray for good cultivation of seeds was propagated along with the expansion and development of horticultural industry, the use of bed soils as growing medium has recently been increased. In this study, the effects of the four clay minerals such as illite, phyllite, zeolite, and bentonite on the early growth of red pepper in the bed soil were investigated. Furthermore, proteome analysis for the leaf and stem samples of red pepper treated with only illite was performed. Of the seedling cultured, the healthy and regular size seeds were selected and cultivated in the pots, after they were treated with four clay minerals. The experiment was performed during the whole six weeks in the glasshouse of the Chungbuk National University. The growth lengths, fresh and dry weights of red pepper were significantly higher in the treatments of illite, phyllite, zeolite, and bentonite than in the control. In addition, the uptake of $K^+$, $Ca^{2+}$, and $Mg^{2+}$ were higher in the treatment of illite, phyllite, zeolite, and bentonite than in the control. The 2-DE patterns for the red pepper by the applications of illite, phyllite, zeolite, and bentonite were similar to each other. Therefore, compared to the samples of control, the proteome analysis for the samples of red pepper treated by only illite were performed. Proteome analysis for red pepper showed that plastid fructose-1, 6-bisphosphate aldolase class 1, aldolase, and glyceraldehydes 3-phosphate dehydrogenase, all of which were involved in the energy metabolism, were highly expressed in leaf tissue by illite treatment. In stem tissue, NAD-dependent formate dehydrogenase involved in energy metabolism, potassium transport protein, and GIA/RGA-like gibberellins response modulator were highly expressed. Based on the results obtained from the proteome analysis, it appears that the proteins specifically and differentially expressed on the illite treatment may be involved in the enhanced growth of red pepper. The identification of some proteins involved in the response of vegetable crops to the treatment of clay mineral can provide new insights that can lead to a better elucidation and understanding of mechanism on their molecular basis.