• Animal Bioscience
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• 제37권7호
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• pp.1289-1302
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• 2024

Objective: There is a strong relationship between the content of beneficial fatty acids in milk and milk fat metabolic activity in the mammary gland. To improve milk quality, it is therefore necessary to study fatty acid metabolism in bovine mammary gland tissue. In adipose tissue, peroxisome proliferator-activated receptor gamma (PPARG), the core transcription factor, regulates the fatty acid metabolism gene network and determines fatty acid deposition. However, its regulatory effects on mammary gland fatty acid metabolism during lactation have rarely been reported. Methods: Transcriptome sequencing was performed during the prelactation period and the peak lactation period to examine mRNA expression. The significant upregulation of PPARG drew our attention and led us to conduct further research. Results: According to bioinformatics prediction, dual-luciferase reporter system detection, real-time quantitative reverse transcription polymerase chain reaction and Western blotting, miR-130a and miR-130b could directly target PPARG and inhibit its expression. Furthermore, triglyceride and oil red O staining proved that miR-130a and miR-130b inhibited milk fat metabolism in bovine mammary epithelial cells (BMECs), while PPARG promoted this metabolism. In addition, we also found that the coexpression of miR-130a and miR-130b significantly enhanced their ability to regulate milk fat metabolism. Conclusion: In conclusion, our findings indicated that miR-130a and miR-130b could target and repress PPARG and that they also have a functional superposition effect. miR-130a and miR-130b seem to synergistically regulate lipid catabolism via the control of PPARG in BMECs. In the long-term, these findings might be helpful in developing practical means to improve high-quality milk.

• 대한의생명과학회지
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• 제24권3호
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• pp.143-149
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• 2018

Excessive exposure to estrogens is the most important risk factor for the development of hormone-sensitive cancers, especially breast cancer. Estrogen stimulates the expression of genes and proteins involved in cell proliferation by binding to estrogen receptor (ER). Another possible mechanism of ER-independent carcinogenicity of estrogens is based on the hydroxylation of estradiol resulting in the formation of catechol estrogens. Catechol estrogen 4-hydroxyestradiol ($4-OHE_2$) is further oxidized to catechol estrogen-3,4-quinones, the major carcinogenic metabolites of estrogens. Evidence increasingly supports the critical role of $4-OHE_2$ in hormonal carcinogenesis via DNA adduct formation or production of reactive oxygen species, which finally contribute to the transformation of normal mammary epithelial cells and the enhanced growth of breast cancer cells. It is also reported that the level of $4-OHE_2$ or its quinones is highly up-regulated in urine or tissues of breast cancer patients. Thus, we highlight the oncogenic roles of $4-OHE_2$ in catechol estrogen-induced breast carcinogenesis.

• Journal of Animal Science and Technology
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• 제46권4호
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• pp.585-592
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• 2004

돼지에 있어서 약 115일간의 임신 기간 중 마지막 40일 동안에 유선 내에서 유액도관(duct), 분비소엽(lobules), 분비낭포(alveoli) 등의 parenchyma 조직이 현저하게 발달하게 되는데, 이는 단백질 호르몬 relaxin과 estrogen의 공동작용에 기인하여 촉진되는 것으로 알려져 있다. 최근에는 면역조직화학적 실험방법을 통해 relaxin hormone이 유선조직 세포(mammary gland parenchyma cells)에 직접적으로 작용하여 lobuloalveolar의 발달을 촉진할 수 있는 가능성을 시사하였다. 즉 Relaxin에 특이적이고 포화 가능한 Relaxin의 결합부위가 lobulo-llveolar 구조 및 유액도관(lactiferous duct)의 상피세포(epithelial cells)뿐만 아니라 혈관세포에서도 존재함을 관찰하였다. 본 연구의 목적은 유선조직 세포에 존재하는 relaxin 결합부위가 기능적으로 활성을 지닌 relaxin 수용체(functional relaxin receptor)인지를 규명하고 동시에 relaxin hormone이 유선조직 세포에 직접적으로 작용하여 lobulo-alveolar의 발달을 촉진하는 지에 대한 직접적인 증거를 제공하는 데 있다. 정상적인 생리주기를 가진 3마리의 생후 7개월 된 잡종재지에 대하여 양쪽 난소를 모두 제거하는 양측난소 절제시술(Bilateral ovariectomy)을 실시하였다.(day 0). 난소 절제시술 후 15일부터(day 15) 29일(day 29)까지 각 개체별로 estradiol benzoate(1 mg/2 ml /Com oil)를 12시간 간격으로 근육주사 하였다. 시술 후 22일째부터(day 22) 순수 정제된 relaxin을 miniature osmotic pump를 통하여 몸의 anterior end로부터 왼쪽부위의 4번째 유선에 일정한 속도(1 ug/hr)로 주입하기 시작하였으며, 동일한 개체의 오른쪽 부위의 4번째 유선에는 동일한 방업으로 생리적 식염수(대조군)을 주입하였다. 난소 절제수술 후 29일째(day 29) 각 개체를 희생하여 젖꼭지의 base로부터 1cm 떨어진 지점에서 osmotic pump의 위치로부터 가까운 parenchyma 조직 시료를 채취하여 약 5-mm cube으로 자른 다음 조직학적 분석을 위한 일반적 조직시료 처리과정을 시행하였다. 조직절편을 Weigert's iron hematoxylin과 함께 염색한 다음 Olympus AH-2 광학현미경을 이용하여 lobulo-alveolar의 발달과 세포외간 섬유사인 collagen의 밀도와 정렬정도를 조사하였다. 생리식염수로 처리된 유선조직에 있어서는 lobulo-alveolar의 발달이 거의 일어나지 못한 반면, relaxin을 처리한 유선조직은 lobulo-alveolar의 현저한 발달을 보였을 뿐만 아니라 분비낭포(alveoli) 내에서는 두드러진 분비물이 존재하였다. 또한 식염수로 처리된 유선조직에서는 비교적 조밀하고 매우 잘 발달된 collagen 섬유사 묶음을 가진 세포의 간 기질의 특징을 보였으나, relaxin 호르몬이 처리된 유선조직에서는 collagen 섬유사가 비교적 분산되어 있고 느슨하며 덜 조밀한 구조적 특징을 나타내었다. 결론적으로, 본 연구의 결과는 유선조직 내의 특이적 relaxin 결합세포가 기능적으로 활성을 지닌 relaxin 수용체를 함유하고 있으며, relaxin hormone이 유선조직 세포에 직접적으로 작용함으로써 lobulo-alveolar의 발달을 촉진함을 보여준다.

• Asian-Australasian Journal of Animal Sciences
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• 제15권4호
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• pp.576-584
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• 2002

Bovine PAS-4 is an integral membrane glycoprotein expressed in mammary epithelial cells. Complementary DNA (cDNA) cloning of PAS-4 was performed by reverse-transcriptase polymerase chain reaction (RT-PCR) with oligonucleotide probes based on it's amino terminal and internal tryptic-peptides. The cloned PAS-4 cDNA was 1,852 nucleotides (nt) long and its open reading frame (ORF) was encoded 1,413 base long. The deduced amino acid sequence indicated that PAS-4 consisted of 471 amino acid residues with molecular weight of 52,796, bearing 8 potential N-glycosylation sites and 9 cysteine residues. Partial bovine CD36 cDNA from liver also was sequenced and the homology of both nucleotide sequence was 94%. Most of the identical amino acid residues were in the luminal/extracellular domains. Contrary to PAS-4, bovine liver CD36 displays 6 potential N-glycosylation sites, which were located, except for those at positions 101 and 171, at same positions as PAS-4 cDNA. Cysteine residues of PAS-4 and CD36 were same at position and in numbers. Northern blot analysis showed that PAS-4 was widely expressed, although its mRNA steady-state levels vary considerably among the analyzed cell types. PAS-4 possessed hydrophobic amino acid segments near the amino- and carboxyl-termini. Two short cytoplasmic tails of the amino- and carboxyl-terminal ends constituted of a 5-7 and 8-11 amino acid residues, respectively.

• 한국식품위생안전성학회지
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• 제21권4호
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• pp.258-262
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• 2006

환경호르몬 물질의 생체내에서의 상호작용에 의한 상자 또는 상승 작용을 알아보기 위하여 환경호르몬 물질들을 조합하여 마우스에 처치한 후 생체내에서 생식기의 변화 정도를 조직병리학적으로 관찰하였다. 암컷 ICR마우스에 난소적출술을 실시하고 2주 후에 DEHP, DBP, BPA의 환경호르몬 물질을 단독 또는 두개씩 조합하여 마우스에 피하로 주입하였다. 육안적인 변화에서는 모든 군에서 이상이 관찰 되지 않았으며, 부검 후 자궁의 무게를 측정한 결과에 있어서도 유의적인 변화를 관찰할 수 없었으나, 자궁 내 fluid존재에 있어서는 E2 단독 투여 군과 E2와 함께 투여한 모든 그룹(E2+DEHP, E2+DBP, E2+BPA)에서 관찰되었다. 조직병리학적인 관찰에 있어서는.자궁상피세포, 질 상피세포, 유선의 변화 그리고 난관 직경의 변화를 관찰하였다. 그 결과 민감도에 있어서 가장 유의적인 변화를 보인 항목은 질 상피세포의 변화였으며, 환경호르몬 물질을 두개씩 혼합하여 처치한 그룹에 있어 단독으로 처치한 그룹과 비교 시 변화의 정도가 심한 것이 일부 관찰 되었으나 통계학적으로 유의성을 가지고 있다고 결론을 내리기 는 힘들었다. 결론적으로 환경호르몬물질간의 생체내에서 상가 혹은 상승작용에 대한 명확한 결과는 도출할 수 없었으나, 환경호르몬물질이 생체내 작용하는 데에 있어서 서로 간에 상승작용을 할 수 있다는 가능성은 충분한 것으로 판단되어진다.

• 대한수의학회지
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• 제41권4호
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• pp.549-555
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• 2001

Indole-3-carbinol (I3C), one component of cruciferous vegetables (the Fammily of Cruciferae), has been shown to exert its chemopreventive effect in liver, colon and mammary tissue before or concurrent exposure of carcinogen, but there have been several evidences that consumption of I3C induced tumor promotion in some tissues. Our studies were investigated to examine the modifying effects of I3C in the 7,12-dimethylbenz[$\alpha$]anthracene (DMBA) induced rat mammary gland tumor model. Fifty-two female Sprague-Dawley rats were randomly divided into five groups. Animals of the group 1 were given the diet containing 100ppm I3C and animals of the groups 2 and 4 were given the diet containing 300ppm I3C from 6 weeks of age. At 7 weeks of age, the animals of the groups 1, 2 and 3 were intubated with DMBA. All amimals were killed at 20 weeks after carcinogen treatment. There were significant increases of food consumption in I3C feeding groups compared with those of basal diet feeding groups. The incidences of the mammary tumors in the group 1, 2 and 3 were 75.0% (9/12), 56.3% (9/16) and 93.8% (15/16), respectively and the average number of tumors of group 1 (DMBA+I3C 100ppm: $2.08{\pm}0.61$) and 2 (DMBA+I3C 300ppm: $1.19{\pm}0.32$) were significantly lower than that of group 3 (DMBA alone: $4.63{\pm}0.72$) at the value of P<0.05 and P<0.001, respectively. In the pathological examination of appearing tumors, most of them were adenocarcinoma. Many epithelial cells of tumors showed strong estrogen receptor (ER) $\alpha$ expression but there were slight difference of ER $\alpha$ expression among the type of tumors. We suggest that pre-initiation treatment of I3C has an inhibitory effects on mammary carcinogenesis induced by DMBA.

• 한국환경성돌연변이발암원학회지
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• 제19권1호
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• pp.56-62
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• 1999

Resveratrol (3,5,4'-trihydroxy-trans-stilbene) has been considered to be as one of major antioxidants present in grapes responsible for beneficial effects of red wine consumption on coronary heart disease. This triphenolic stilbene has been suggested as a potential cancer chemopreventive agent based on its striking inhiitory effects on diverse cellular events associated with tumor initiation, promotion, and progression. The compound has strong antioxidative and anti-inflammatory activities which amy contribute to its chemopreventive/chemoprotective properties. In the present work, we have found that resveratrol reduces viability and DNA synthesis capability of cultured human promyelocytic leukemia (HL-60) cells. Likewise, the viability of human breast cancer cell line, MCF-7 was reduced by resveratrol treatment. The growth inhibitory and antiproliferative properties of resveratrol appear to be associated with its induction of apoptotic cell death as determined by morphological and ultrastructural changes, agarose gel electrphoretic analysis of internucleosomal DNA fragmentation, and in situ terminal end-labeling of fragmented DNA (TUNEL). This compound also inhibited the phorbol ester-induced expression of cyclooxygenase-2 (COX-2) protein in immortalized human mammary epithelial MCF-10A cells. These results suggest that resveratrol has the promising cancer therapeutic/chemopreventive potential.

• Natural Product Sciences
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• 제27권1호
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• pp.49-53
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• 2021

Balanophora laxiflora Hemsl. (Balanophoraceae) is a traditional medicinal plant with a diverse array of biological activities. In our exploration of new bioactive constituents from B. laxiflora, we isolated five compounds, including a new lignan, balanophorone (5), and four known phenolic compounds (1-4). The chemical structures of these compounds were determined by extensive spectroscopic analyses, including 1D and 2D NMR, HR-ESI-MS, and CD. In addition, we evaluated the effects of each of the isolates (1-5) on the messenger RNA expression levels of tumor necrosis factor (TNF)-α and cyclooxygenase (COX)-2 in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages and cytotoxicity against MCF-7 and MDA-MB-231 breast cancer cells. Compound 2 showed significant inhibition of LPS-induced COX-2 and TNF-α expression in RAW 264.7 macrophages, while compound 4 showed moderate cytotoxicity against MCF-7 and MDA-MB-231 breast cancer cells, with IC50 values of 18.3 and 30.7 µM, respectively. No significant effects on the viability of normal mammary epithelial cells were observed.

• 한국독성학회:학술대회논문집
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• 한국독성학회 2001년도 International Symposium on Dietary and Medicinal Antimutgens and Anticarcinogens
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• pp.52-53
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• 2001

In order for vitamin D to be active, it needs to get metabolized to 1, 25 (OH)$_2$D3. This active metabolite of vitamin D induces epithelial cell differentiation and is antiproliferative. However, at the efficacious concentration, the natural ligand for VDR is hypercalcemic and toxic to cells. Therefore, numerous analogs have been synthesized with the hope of generating a compound that retains vitamin D activity and is non-toxic.(omitted)

• 한국독성학회:학술대회논문집
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• 한국독성학회 2001년도 International Symposium on Effects of Edible Phytochemicals and Their Synthetic Derivatives on Carcinogenesis and Mutagenesis
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• pp.9-10
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• 2001

In order for vitamin D to be active, it needs to get metabolized to 1, 25 (OH)$_2$D3. This active metabolite of vitamin D induces epithelial cell differentiation and is antiproliferative. However, at the efficacious concentration, the natural ligand for VDR is hypercalcemic and toxic to cells. Therefore, numerous analogs have been synthesized with the hope of generating a compound that retains vitamin D activity and is non-toxic.(omitted)