• Title/Summary/Keyword: Physiological Activities

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Effect of Nardostachyos Rhizoma on Apoptosis, Differentiation and Proliferation in HL-60 cells

  • Ju Sung-Min;Lee Jun;Choi Ho-Seung;Yoon Sang-Hak;Kim Sung-Hoon;Jeon Byung-Hun
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.20 no.1
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    • pp.163-170
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    • 2006
  • Nardostachyos Rhizoma (N. Rhizoma) belonging to the family Valerianaceae has been anti-arrhythmic effect, and sedation to the central nerve and a smooth muscle. We reported that the water extract of N. Rhizoma induced apoptotic cell death and differentiation in human promyelocytic leukemia (HL-60) cells. Cytotoxicity of N. Rhizoma was detected only in HL-60 cells (IC50 is about 200 ${\mu}g/ml$). The cytotoxic activity of N. Rhizoma in HL-60 cells was increased in a dose-dependent manner. We used several measures of apoptosis to determine whether these processes were involved in N. Rhizoma-induced apoptotic cell death. The high-dose (200 ${\mu}g/ml$) treatment of N. Rhizoma to HL-60 cells showed cell shrinkage, cell membrane blobbing, apoptotic bodies, and the fragmentation of DNA, suggesting that these cells underwent apoptosis. Treatment of HL-60 cells with N. Rhizoma time-dependently induced activation of caspase-3, caspase-8, and caspase-9 and proteolytic cleavage of poly(ADP-ribose) polymerase. Also, we investigated the effect of N. Rhizoma on cellular differentiation and proliferation in HL-60 cells. Differentiation and proliferation of HL-60 cells was determined through expression of CD11b and CD14 surface antigens using flow cytometry and nitroblue tetrazolium (NBT) assay, and through analysis of cell cycle using propidium iodide assay, respectively. N. Rhizoma induced the differentiation of HL-60 at the low-dose (100 ${\mu}g/ml$) treatment, as shown by increased expression of differentiation surface antigen CD11b, but not CDl4 and increased reducing activity of NBT. When HL-60 cells were treated with N. Rhizoma at concentration of $50{\mu}g/ml\;and\;100{\mu}g/ml$, NBT-reducing activities induced approximately 1.5-fold and 20.0-fold as compared with the control. In contrast, HL-60 cells treated with the N. Rhizoma-ATRA combination showed markedly elevated levels of 26.3-fold at $50{\mu}g/ml$ N. Rhizoma-0.1 ${\mu}M$ ATRA combination and 27.5-fold at 50 ${\mu}g/ml$ N. Rhizoma-0.2 ${\mu}M$ ATRA combination than when treated with N. Rhizoma alone or ATRA alone. It may be that N. Rhizoma plays important roles in synergy with ATRA during differentiation of HL-60 cells. DNA flow-cytometry indicated that N. Rhizoma markedly induced a G1 phase arrest of HL-60 cells. N. Rhizoma-treated HL-60 cells increased the cell population in G1 phase from 32.71% to 42.26%, whereas cell population in G2/M and S phases decreased from 23.61% to 10.33% and from 37.78% to 33.98%, respectively. We examined the change in the $p21^{WAF1/Cip1}\;and\;p27^{Kip1}$ proteins, which are the CKIs related with the G1 phase arrest. The expression of the CDK inhibitor $p27^{Kip1},\;but\;not\;p21^{WAF1/Cip1}$ were markedly increased by N. Rhizoma. Taken together, these results demonstrated that N. Rhizoma induces apoptotic cell death through activation of caspase-3, and potently inhibits the proliferation of HL-60 cells via the G1 phase cell cycle arrest in association with $p27^{Kip1}$ and granulocytic differentiation induction .

Inhibition of Lipopolysaccharide-Inducible Nitric Oxide Synthase, $TNF-{\alpha}$, $IL-1{\beta}$ and COX-2 Expression by Flower and Whole Plant of Lonicera japonica (금은화(金銀花) 및 금은화전초(金銀花全草)가 Raw 264.7 cell에서 LPS로 유도된 NO의 생성, iNOS, COX-2 및 cytokine에 미치는 영향)

  • Lee, Dong-Eun;Lee, Jae-Ryung;Kim, Young-Woo;Kwon, Young-Kyu;Byun, Sung-Hui;Shin, Sang-Woo;Suh, Seong-Il;Kwon, Taeg-Kyu;Byun, Joon-Seok;Kim, Sang-Chan
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.19 no.2
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    • pp.481-489
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    • 2005
  • Lonicerae Flos has antibacterial effects against Staphylococcus aureus, streptococci, pneumococci, Bacillus dysenterii, Salmonella typhi, and paratyphoid. It is an antiviral agent. The herb has a cytoprotective effect against $CCl_{4}-induced$ hepatic injury. It has antilipemic action, interfering with lipid absorption from the gut. Nowadays this herb is used mainly in the treatment of upper respiratory infections, such as tonsillitis and acute laryngitis. It is also used in the treatment of skin suppurations, such as carbuncles, and to treat viral conjunctivitis, influenza, pneumonia, and mastitis. Lonicerae Flos is dried flower buds of Lonicera japonica, L. hypoglauca, L. confusa, or L. dasystyla. But, for the most part, we use whole plant of Lonicera japonica, as a flower bud of it. And, little is known of the original copy of effects of whole plant, except for the 'Bon-Cho-Gang-Mok', which is written the effects of flower of Lonicera japonica are equal to effects of leaves and branch of it. The present study was conducted to evaluate the effect of flower and whole plant of Lonicera japonica on the regulatory mechanism of cytokines, inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX-2) for the immunological activities in Raw 264.7 cells. In Raw 264.7 cells stimulated with lipopolysaccharide (LPS) to mimic inflammation, flower and whole plant of Lonicera japonica water extracts inhibited nitric oxide production in a dose-dependent manner and abrogated iNOS and COX-2. Flower and whole plant of Lonicera japonica water extract did not affect on cell viability. To investigate the mechanism by which flower and whole plant of Lonicera japonica water extract inhibits iNOS and COX-2 gene expression, we examined the on phosphorylation of inhibitor ${\kappa}B{\alpha}$ and assessed production of $TNF-{\alpha}$, $interleukin-1{\beta}$ $(IL-1{\beta})$ and interleukin-6 (IL-6). Results provided evidence that flower and whole plant of Lonicera japonica inhibited the production of $IL-1{\beta}$, IL-6 and activated the phosphorylation of inhibitor ${\kappa}B{\alpha}$ in Raw 264.7 cells activated with LPS. These findings suggest that flower and whole plant of Lonicera japonica can produce anti-inflammatory effect, which may play a role in adjunctive therapy in Gram-negative bacterial infections, respectively.

Assessment of Nutritional Components, Carotenoid Content and Physiological Activity of Maize Hybrid for Grain 'Kangilok' (강일옥 옥수수의 영양성분, 카로티노이드 함량분석 및 생리활성 평가)

  • Lee, Ki Yeon;Kim, Jai Eun;Hong, Soo Young;Kim, Tae Hee;Park, A-Reum;Noh, Hee Sun;Kim, Si Chang;Park, Jong Yeol;Ahn, Mun Seob;Kim, Hee Yeon
    • Journal of Food Hygiene and Safety
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    • v.32 no.6
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    • pp.513-520
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    • 2017
  • This study was performed to provide basic data of 'Kangilok'. The objective of this study was to investigate worth of 4 parts of maize hybrid for grain, 'Kangilok' for functional foods. The 4 parts are kernels, dehulled kernels, skin of kernels and cobs of 'Kangilok'. We evaluated moisture, crude ash, crude lipid, crude protein, crude fiber and mineral content of 'Kangilok'. The moisture of kernels, dehulled kernels, skin of kernels and cobs of 'Kangilok' were 11.27%, 12.40%, 9.45%, 8.85% and the crude ash were 1.26%, 0.73%, 3.19%, 1.42%. Each of the crude lipid were 3.84%, 2.69%, 8.59%, 0.46% and the crude protein were 9.40%, 9.96%, 12.10%, 2.80%. The crude fiber of kernels, dehulled kernels, skin of kernels and cobs of 'Kangilok' were 2.24%, 0.92%, 7.07%, and 33.51%. Among the mineral contents, Ca and K content of cobs were highest by 4.84 mg/100 g, 114.33 mg/100 g and Fe, Mn contents of skin of kernels were highest by 5.30 mg/100 g, 2.64 mg/100 g. Mg content of kernels was the highest by 27.42 mg/100 g. P content of kernels, dehulled kernels, skin of kernels and cobs were 1.20%, 0.96%, 2.41%, and 0.19%. It was performed test on anti-oxidative, anti-inflammatory activities of 60% ethanol extract from 4 parts of Kangilok. The anti-oxidative effect was measured by DPPH and ABTS radical scavenging activity. As a results, DPPH radical scavenging activity (10 mg/mL) was 72.59%~93.05% and ABTS radical scavenging activity (10 mg/mL) was 48.17%~79.88%. The anti-inflammatory effect was measured by ability to inhibit production nitric oxide (NO) in RAW264.7 cell. As a result, all the extract of 4 parts were showed significantly inhibitory effect on NO production. Carotenoid contents quantified by using HPLC. ${\beta}$-Carotene of carotenoid was not analyzed in all the sample. Lutein and zeaxantin ware analyzed in kernels and skin of kernels.

Protective effect of Eucommia ulmoides oliver leaves against PM2.5-induced oxidative stress in neuronal cells in vitro (미세먼지(PM2.5)로 유도된 산화적 스트레스에 대한 두충(Eucommia ulmoides Oliver) 잎의 in vitro 뇌 신경세포 보호 효과)

  • Kim, Min Ji;Kang, Jin Yong;Park, Seon Kyeong;Kim, Jong Min;Moon, Jong Hyun;Kim, Gil Han;Lee, Hyo Lim;Jeong, Hye Rin;Heo, Ho Jin
    • Korean Journal of Food Science and Technology
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    • v.53 no.4
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    • pp.423-433
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    • 2021
  • This study was performed to examine the neuroprotective effect of the ethyl acetate fraction from Eucommia ulmoides oliver leaf (EFEL) on PM2.5-induced cytotoxicity. EFEL had higher total phenolic and flavonoid contents than the other fractions. In ABTS and DPPH radical scavenging activities, the IC50 of EFEL was measured as 212.80 and 359.13 ㎍/mL, respectively. To investigate the neuroprotective effect of EFEL, MTT and DCF-DA assays were performed on HT22, MC-IXC, and BV-2 cells. EFEL effectively decreased PM2.5-induced intercellular reactive oxygen species (ROS) content and inhibited PM2.5-induced cell death. In the results of protein expression related to cellular cytotoxicity on microglial cells (BV-2), EFEL had an improvement effect on cell apoptosis and inflammatory pathways. Rutin and chlorogenic acid were identified as the main physiological compounds. Moreover, it was expected that EFEL, including rutin and chlorogenic acid, could be functional food substances with neuroprotective effects against PM2.5-induced oxidative stress.

Assessment of Nutritional Components, Antioxidant Contents and Physiological Activity of Purple Corn Husk and Cob Extracts (자색옥수수 포엽과 속대 혼합 추출물의 영양성분, 항산화 활성 물질 함량분석 및 생리활성 평가)

  • Lee, Ki Yeon;Kim, Tae hee;Kim, Jai Eun;Park, A-Reum;Noh, Hee Sun;Kim, Si Chang;Ahn, Mun Seob;Kim, Hee Yeon
    • Journal of Food Hygiene and Safety
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    • v.33 no.6
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    • pp.500-509
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    • 2018
  • The objective of this study was to investigate the worth of extract husk and cobs of the Seakso 1 (EHCS) for the functional foods. We aimed to investigate the proximate composition, fatty acids, amino acids, antioxidant active substance contents, antioxidant activity, inhibitory activity of the ${\alpha}-amylase$ and ${\alpha}-glucosidase$. The proximate composition of the EHCS have represented 6.90% moisture, 7.31% crude ash, 0.52% crude fat and 7.07% crude protein. Among the 17 kinds of amino acids that were analyzed in thd EHCS, the glutamic acid was the highest, with 736.08 mg / 100 g. The fatty acids detected in the EHCS were palmitic acid oleic acid and linoleic acid. The proportion of the unsaturated fatty acids was 83.33%. We determined the contents of the antioxidant active substance by the total polyphenol and flavonoid. The total polyphenol and flavonoid contents were 99.87 mg/g and 25.02 mg/g, respectively. The antioxidative activity of the EHCS were determined using a DPPH and ABTS assay. In the antioxidative activity determination, the DPPH and ABTS radical scavenging activities were 95.62% ($1,000{\mu}g/mL$) and 92.00% ($10,000{\mu}g/mL$), respectively. The inhibitory activity of ${\alpha}-amylase$ and ${\alpha}-glucosidase$ (10 mg/mL) were 95.86% and 76.92%, respectively. These results suggest that the EHCS could be potentially used as a resource for the bioactive materials for health functional foods.

Biological Characteristics of Protein Hydrolysates Derived from Yoensan Ogae Meat by Various Commercial Proteases (프로테아제 종류에 따른 이용한 연산 오계육 단백질 가수분해물의 아미노산 및 생리활성 특성)

  • Ha, Yoo Jin;Kim, Joo Shin;Yoo, Sun Kyun
    • Journal of the Korean Applied Science and Technology
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    • v.36 no.3
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    • pp.1018-1027
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    • 2019
  • Natural-derived protein-derived low molecular weight peptides have been known to have physiological activities such as antioxidant, hypertension relief, immunomodulation, pain relief and antimicrobial activity. In this study, the low-molecular peptides were produced using commercial proteases (alcalase, bromelain, flavourzyme, neutrase, papain, protamex), and the antioxidant activity (DPPH scavenging activity, superoxide radical scavenging activity, hydroxy radical scavenging activity, and metals chelation capacity), constituent amino acid and molecular weight of the peptide were analyzed. Enzyme reaction was performed by adding 50 g of chopped Ogae meat slurry and 2%(w/v) protein enzyme into the enzyme reactor for 2 h at a pH of 6 and a temperature of $60^{\circ}C$. The degree of hydrolysis(%) after the reaction ranged from $36.65{\pm}4.10%$ to $70.75{\pm}5.29%$. The highest degree of hydrolysis of protamex was 46.3%, and the highest value of papain hydrolysate was $70.75{\pm}5.29%$. On the other hand, alcalase hydrolysate showed the lowest value of $36.65{\pm}4.10%$. Bromelain-treated low molecular weight peptides showed the highest DPPH radical scavenging activity and the lowest scavenging activity of alcalase-treated peptides. Superoxide radical scavenging activity showed that bromelain treated low molecular peptide showed the highest radical scavenging activity of 50% or more. Hydroxyl radical scavenging activity ranged from about 16.73 to 69.16%, the highest among bromelain-treated low molecular peptides. $Fe^{2+}$ chelation abilities showed a distribution between about 17.85 to 47.84%. The chelation capacity of the hydrolysates was not significantly different without any difference to the enzymes used. The results of amino acid analysis showed differences between hydrolysates of alcalase, bromelain, flavourzyme, neutrase, papain, and protamex enzymes. The most amino acid was glutamic acid. The molecular weight distribution of the enzyme hydrolyzates was in the range of 300-2,000 Da, although the molecular weight distribution differed according to the treated enzymes.

Protein and Arabinoxylan Contents of Whole Grains from Wheat Genetic Resources Cultivated in Korea (국내에서 재배된 밀 유전자원의 통밀에서 단백질 및 아라비노자일란 함량 분석)

  • Yang, Jinwoo;Park, Jinhee;Son, Jae-Han;Kim, Kyeong-Hoon;Kim, Kyeong-Min;Jeong, Han-Yong;Kang, Chon-Sick;Son, Ji-Young;Park, Tae-Il;Choi, Changhyun
    • KOREAN JOURNAL OF CROP SCIENCE
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    • v.66 no.1
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    • pp.29-36
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    • 2021
  • Recently, phytochemicals in whole grains have received increasing attention because the increased consumption of whole grains and whole grain products has been associated with a reduced risk of chronic diseases. Among the phytochemicals in whole wheat, arabinoxylan influences various physiological activities and can aid the treatment of numerous health conditions, either directly or indirectly. In this study, 614 wheat germplasms, collected from the world, were cultivated in 2018 and harvested in 2019 in South Korea. The qualities of these whole grains, including seed protein content, were evaluated using the NIR spectrophotometric method, and arabinoxylan content was determined using enzymatic methods. The ash content was 0.36 to 2.80% and protein content was 7.66 to 20. The SDS-sedimentation for gluten complex ability ranged from 26.85 to 80.63 mL, and protein content showed a high correlation with SDS-sedimentation in the germplasms. Verify the result of the enzymatic method of arabinoxylan, the reliability of the experimental method was determined through repeatability, reproducibility, and recovery. The average value of the 614 resources was 51.64 mg/g of whole grain, and when classified according to the country of origin, the South Korean origin resources tended to have a higher content compared to the genetic resources of other countries. These results are expected to be used as basic data for setting standards for whole grain quality in wheat breeding systems.

Changes in Abscisic Acid and Gibberellin Levels during Stratification in Panax ginseng Roots (인삼근의 휴면타파과정에 있어서 Abscisic acid 함량 및 Gibberellin 활성의 변화)

  • Choi, Sun-Young;Lee, Kang-Soo;Ryu, Jeom-Ho
    • KOREAN JOURNAL OF CROP SCIENCE
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    • v.34 no.1
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    • pp.7-13
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    • 1989
  • The present study was carried out to get the basic information for clarifying physiological mechanism of breaking dormancy and sprouting in Panax ginseng roots. Changes in Abscisic acid (ABA) content and Gibberellin (GA) activity were investigated in one-year-old root during stratification at 4$^{\circ}C$. 15$^{\circ}C$. and 15$^{\circ}C$ after 60day-treatment at 4$^{\circ}C$. Sprouting rate at 15$^{\circ}C$ was 35% in 30days storage at 4$^{\circ}C$ and 100% in longer than 60days, but there was no sprout in both the constant treatment at 4$^{\circ}C$ or 15$^{\circ}C$ regardless of the treatment period. The longer the period of low temperature treatment. number of days to the first and 50% sprouting was shortened, and number of days to 50% from first sprouting was also shortened. ABA content in the upper part of root(contained bud) was gradually increased at both 4$^{\circ}C$ and 15$^{\circ}C$ as the treatment period was extended. and the degree of increase was higher at 15$^{\circ}C$. In the lower part. it showed a slight increase at 15$^{\circ}C$. while showed little change at 4$^{\circ}C$ throughout the treatment period. In the 15$^{\circ}C$ treatment after 60days at 4$^{\circ}C$, it was greatly increased in the upper part. while rather slightly decreased in the lower part of root. GA activity in the upper part was gradually decreased at both 4$^{\circ}C$ and 15$^{\circ}C$, and the degree of decrease was higher at 15$^{\circ}C$. In the lower part. it was similar tendency to those in the upper part. In the 15$^{\circ}C$ treatment after 60days at 4$^{\circ}C$. it was remarkably increased in both the upper and lower part. The increase was great in the low Rf region, while the decrease appeared relatively in the high Rf region compared to those of 60day-treatment at 4$^{\circ}C$. The above results indicated that the breaking dormancy and sprouting of bud were closely associated with the degree of GA activities in response to temperature condition .during stratification rather than the direct effect associated with the changes in ABA content.

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Effect of Acute Ethanol Intoxication on the Pulmonary Compliance and Surfactant in Rats (급성(急性) Ethyl 알콜 중독(中毒) 흰쥐의 폐용압률(肺容壓率)과 폐포활성물질(肺胞活性物質)의 변화(變化))

  • Lee, Seung-Jung;Choo, Young-Eun
    • The Korean Journal of Physiology
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    • v.15 no.1
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    • pp.27-36
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    • 1981
  • Relatively little has been done on the metabolic changes of the lung produced by the excessive alcohol ingestion to the point of the acute alcohol intoxication. In the present study, an effort was made to clarify the possible changes of the pulmonary surfactant system by the acute alcohol ingestion. The dynamic pulmonary compliance and the levels of protein and inorganic phosphorus (Pi) of both lung lavage and extract were chosen as the parameters of the pulmonary surfactant activities. The albino rats of both sexes were used, and 1.5 ml of 50% ethanol per 100 g body weight was given by oral intubation, and the experiment was performed at 1, 3, 6, 12, and 24 hours after the alcohol ingestion. The rat was sacrificed by cutting the carotid arteries, and blood sample for the determination of hematocrit(Hct) and the blood alcohol concentration was obtained. Both lungs were completely removed without dammage to the lung tissue, and the pulmonary compliance was measured by the changes of pressure-volume(P-V) curves by inflating or deflating the lung with air. Immediately after the P-V curves were recorded, the lung lavage was obtained by washing the lobes with 15ml of isotonic saline 3 times with a syringe. Next, total lungs were homogenized and filtered to obtain the lung extract. The protein and Pi levels were measured using the lung lavage and extract as the samples, and the lung/body weight ratio(L/B ratio) was also calculated. The results thus obtained were compared with the normal values and summarized as follows. The blood alcohol concentration reached the highest level of $0.71{\pm}0.02\;g\;%$ at 1 hr and gradually decreased until 24 hrs$(0.36{\pm}0.02\;g%)$ after the alcohol ingestion, but all the experimental groups showed significant increase comparing with the normal. The highest Hct value was obtained at 1hr$(64.86{\pm}2.45%)$ and significantly elevated value was continued throughout the experiment. The L/B ratio was significantly lowered from 3hrs until 24hrs after the alcohol ingestion but from 6 th hr on, a generally elevated value was observed with a significant value at 12 hrs and gradual recovery to the normal value at 24 hrs after the alcohol ingestion. The pulmonary compliance at inflation and deflation did not change appreciablly from the normal until 3 hrs after the alcohol ingestion but from 6 th hr on, a generally elevated value was observed with a significant value at 12 hrs and gradual recovery to the normal value at 24 hrs after the alcohol ingestion. The protein level of the lung lavage stowed a significantly increased value of $12.36{\pm}0.35\;mg/gm(3rd hr)$, $12.70{\pm}0.74\;mg/gm(12 th hr)$, and $12.65{\pm}0.88\;mg/gm(24 th hr)$, respectively, comparing with the normal value of $10.65{\pm}0.62\;mg/gm$, and the Pi level also showed a similar tendency of significant increase at 12th hr $(7.65{\pm}0.63\;{\mu}mol/gm)$ and 24 th hr$(6.70{\pm}0.36\;{\mu}mol/gm)$ comparing with the normal value of $5.32{\pm}0.20\;{\mu}mol/gm$. The protein level of the lung extract in the alcohol group was generally similar to the normal value with a slight decrease at 1st and 3 rd hr, tut the Pi level of the lung extract was generally increased in the alcohol group, and a significant increase was observed at 6 th hr$(17.77{\pm}1.54\;{\mu}mol/gm)$, 12 th hr$(13.92{\pm}0.78\;{\mu}mol/gm)$ and 24 th hr$(14.57{\pm}0.53\;{\mu}mol/gm)$ of the alcohol ingestion comparing with the normal value of $10.34{\pm}0.37\;{\mu}mol/gm$. From the above, it may be concluded that the acute alcohol intoxication produces the metabolic changes of the lungs by the increased surfactant activities and elevated pulmonary compliance.

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Roles of the Insulin-like Growth Factor System in the Reproductive Function;Uterine Connection (Insulin-like Growth Factor Systems의 생식기능에서의 역할;자궁편)

  • Lee, Chul-Young
    • Clinical and Experimental Reproductive Medicine
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    • v.23 no.3
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    • pp.247-268
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    • 1996
  • It has been known for a long time that gonadotropins and steroid hormones play a pivotal role in a series of reproductive biological phenomena including the maturation of ovarian follicles and oocytes, ovulation and implantation, maintenance of pregnancy and fetal growth & development, parturition and mammary development and lactation. Recent investigations, however, have elucidated that in addition to these classic hormones, multiple growth factors also are involved in these phenomena. Most growth factors in reproductive organs mediate the actions of gonadotropins and steroid hormones or synergize with them in an autocrine/paracrine manner. The insulin-like growth factor(IGF) system, which is one of the most actively investigated areas lately in the reproductive organs, has been found to have important roles in a wide gamut of reproductive phenomena. In the present communication, published literature pertaining to the intrauterine IGF system will be reviewed preceded by general information of the IGF system. The IGF family comprises of IGF-I & IGF-II ligands, two types of IGF receptors and six classes of IGF-binding proteins(IGFBPs) that are known to date. IGF-I and IGF-II peptides, which are structurally homologous to proinsulin, possess the insulin-like activity including the stimulatory effect of glucose and amino acid transport. Besides, IGFs as mitogens stimulate cell division, and also play a role in cellular differentiation and functions in a variety of cell lines. IGFs are expressed mainly in the liver and messenchymal cells, and act on almost all types of tissues in an autocrine/paracrine as well as endocrine mode. There are two types of IGF receptors. Type I IGF receptors, which are tyrosine kinase receptors having high-affinity for IGF-I and IGF-II, mediate almost all the IGF actions that are described above. Type II IGF receptors or IGF-II/mannose-6-phosphate receptors have two distinct binding sites; the IGF-II binding site exhibits a high affinity only for IGF-II. The principal role of the type II IGF receptor is to destroy IGF-II by targeting the ligand to the lysosome. IGFs in biological fluids are mostly bound to IGFBP. IGFBPs, in general, are IGF storage/carrier proteins or modulators of IGF actions; however, as for distinct roles for individual IGFBPs, only limited information is available. IGFBPs inhibit IGF actions under most in vitro situations, seemingly because affinities of IGFBPs for IGFs are greater than those of IGF receptors. How IGF is released from IGFBP to reach IGF receptors is not known; however, various IGFBP protease activities that are present in blood and interstitial fluids are believed to play an important role in the process of IGF release from the IGFBP. According to latest reports, there is evidence that under certain in vitro circumstances, IGFBP-1, -3, -5 have their own biological activities independent of the IGF. This may add another dimension of complexity of the already complicated IGF system. Messenger ribonucleic acids and proteins of the IGF family members are expressed in the uterine tissue and conceptus of the primates, rodents and farm animals to play important roles in growth and development of the uterus and fetus. Expression of the uterine IGF system is regulated by gonadal hormones and local regulatory substances with temporal and spatial specificities. Locally expressed IGFs and IGFBPs act on the uterine tissue in an autocrine/paracrine manner, or are secreted into the uterine lumen to participate in conceptus growth and development. Conceptus also expresses the IGF system beginning from the peri-implantation period. When an IGF family member is expressed in the conceptus, however, is determined by the presence or absence of maternally inherited mRNAs, genetic programming of the conceptus itself and an interaction with the maternal tissue. The site of IGF action also follows temporal (physiological status) and spatial specificities. These facts that expression of the IGF system is temporally and spatially regulated support indirectly a hypothesis that IGFs play a role in conceptus growth and development. Uterine and conceptus-derived IGFs stimulate cell division and differentiation, glucose and amino acid transport, general protein synthesis and the biosynthesis of mammotropic hormones including placental lactogen and prolactin, and also play a role in steroidogenesis. The suggested role for IGFs in conceptus growth and development has been proven by the result of IGF-I, IGF-II or IGF receptor gene disruption(targeting) of murine embryos by the homologous recombination technique. Mice carrying a null mutation for IGF-I and/or IGF-II or type I IGF receptor undergo delayed prenatal and postnatal growth and development with 30-60% normal weights at birth. Moreover, mice lacking the type I IGF receptor or IGF-I plus IGF-II die soon after birth. Intrauterine IGFBPs generally are believed to sequester IGF ligands within the uterus or to play a role of negative regulators of IGF actions by inhibiting IGF binding to cognate receptors. However, when it is taken into account that IGFBP-1 is expressed and secreted in primate uteri in amounts assessedly far exceeding those of local IGFs and that IGFBP-1 is one of the major secretory proteins of the primate decidua, the possibility that this IGFBP may have its own biological activity independent of IGF cannot be excluded. Evidently, elucidating the exact role of each IGFBP is an essential step into understanding the whole IGF system. As such, further research in this area is awaited with a lot of anticipation and attention.

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