• 제목/요약/키워드: PCNA (proliferating cell nuclear antigen)

검색결과 108건 처리시간 0.027초

Urethane으로 유발된 생쥐 폐샘암종 발생과정에서 Caspase 3, Survivin과 p53 단백 발현 (Expression of Caspase 3, Survivin, and p53 Protein in Urethane Induced Mouse Lung Carcinogenesis)

  • 신종욱;이수환;박언섭
    • Tuberculosis and Respiratory Diseases
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    • 제63권3호
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    • pp.251-260
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    • 2007
  • 연구배경 및 목적: ICR계의 생쥐에 Urethane을 투여하여 발생되는 폐 병변의 형태변화를 관찰하고, 폐 샘암종으로 진행과정에서 세포증식능과 세포자멸사, 세포자멸사와 관련된 조절인자인 caspase3, 자멸사 억제인자인 survivin, 그리고 종양억제 유전자 산물인 p53 단백질이 발암과정에서 발현되는 양상을 관찰함으로써 발암과정에서의 역할을 규명하고자 하였다. 방법: Urethane을 ICR 생쥐에게 복강 내 주사를 하였고, 5주, 15주, 25주에 폐병변을 육안적으로 헤마토실린 및 에오신 염색을 관찰하였고, 면역조직화학적 방법으로 PCNA지수, 세포자멸사 지수, capase 3, survivin 및 p53의 발현을 관찰하였다. 결과: Urethane 투여 5주부터 폐의 증식이 관찰되었고, 샘종은 10주 이후부터 출현하여 시간 경과에 따라 크기와 구조적 변화가 동반되었고, 세포학적 이상소견과 더불어 주변으로 침윤성 변화가 있는 샘암종은 25주 이후에 출현하였다. 세포증식능과 세포자멸사 지수는 폐의 증식증에서는 9.6%와 0.24%, 샘종에서는 23.2%와 1.25%, 그리고 샘암종에서는 55.7%와 5.21%이었다. 따라서 세포증식능과 세포자멸사는 폐 샘암종 발생초기부터 통계적으로 유의하게 지속적으로 증가하였고, 특히 샘암종으로 진행할 경우 현저하게 증가하였다. caspase 3는 증식증에서는 15%, 샘종은 16%의 발현율을 보이는 반면, 폐샘암종은 46.7%의 발현율을 보이면서 암 단계에서 현저하게 발현이 증가하였다. Survivin 단백의 발현은 폐의 증식증, 샘종, 그리고 샘암종으로 진행할수록 발현빈도가 통계적의로 유의하게 증가하였다. p53 단백은 폐의 증식증과 샘종에서는 전혀 발현되지 않았으나 침윤성 샘암종의 일부에서 발현되었다. 이상의 결과로 생쥐의 폐샘암종 발생과정에서 세포증식능과 세포자멸사는 종양의 발생과 진행과정에서 지속적으로 관여함을 알 수 있었다. 또한 survivin 발현은 샘암종의 초기단계에서부터 지속적으로 관여하며, p53 유전자 변이는 초기보다는 암종으로 형질전환이 일어난 후에 부분적으로 발생하는 것으로 보인다. 결론: 본 연구를 통하여 PCNA와 세포자멸사 지수는 암세포로 형질전환하는 위험도를 평가하는 지표로 유용할 것으로 보이며, caspase, survivin과 p53는 urethane에 의해 유도된 생쥐 폐암 모델에서 발암과정에 중요하게 관여하는 단백질로 보인다.

소아 Helicobacter pylori 감염에서 위 상피세포의 증식과 세포사 (Gastric Epithelial Cell Proliferation and Apoptosis in Children with Helicobacter pylori Infection)

  • 정지아;김철;한운섭;서정완
    • Pediatric Gastroenterology, Hepatology & Nutrition
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    • 제5권1호
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    • pp.1-10
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    • 2002
  • 목적: 소아기는 알코올이나 약물 등에 의한 자극이 거의 없는 시기로 H. pylori 감염의 자연 경과와 단기간의 영향을 연구하기에 적합한 시기이다. 최근 H. pylori 감염의 기전으로 중요시되고 있는 위상피세포 증식과 세포사에 대해 소아에서 알아보고자 하였다. 방법: 1996년 5월부터 2001년 6월까지 이화여자대학교 목동병원 소아과에서 소화기 증상으로 내시경을 시행하여 H. pylori 감염으로 진단된 58예와 감염 음성 40예를 대상으로 하였다. H. pylori 감염 양성은 조직학적으로 H. pylori 균이 관찰되고, CLO 검사와 ureC PCR이 전부 양성인 경우로 하였다. 위생검 조직에서 개정된 시드니 체계를 이용하여 조직 소견을 분석하고, proliferating cell nuclear antigen (PCNA) 발현으로 위 상피세포 증식의 정도를, in situ terminal deoxynucleotidyl transferasemediated dUTP nick-end labeling (TUNEL) 방법으로 세포사의 정도를 조사하였다. 결과: 1) H. pylori 감염 양성에서 다핵형 중성구의 활동성(P=0.000), 만성 염증(P=0.000), 상피손상(P=0.000), 림프여포(P=0.000)의 정도가 감염 음성에 비하여 유의하게 높았다. H. pylori 감염 양성에서 장형화생은 관찰되지 않았다. 2) H. pylori 감염 양성에서 세포 증식 지표는 $67.8{\pm}18.13$으로, 음성 $54.8{\pm}14.46$에 비하여 유의하게 높았다(P=0.000). 세포 증식 지표는 H. pylori 밀도가 증가할수록(r=0.277, P=0.007), 다핵형 중성구의 활동성이 증가할수 (r=0.280, P=0.007), 만성염증이 증가할수록(r=0.284, P=0.006) 증가하였다. 3) 세포사 지표는 H. pylori 감염 양성에서 $0.44{\pm}0.447$, 음성에서 $0.14{\pm}0.196$으로 감염 양성에서 음성보다 유의하게 높았다(P=0.000). 세포사 지표는 H. pylori 밀도가 증가할수록(r=0.472, P=0.000), 다핵형 중성구의 활동성이 증가할수록(r=0.370, P=0.001), 만성 염증이 증가할수록(r=0.483, P=0.000) 증가하였다. 4) 세포 증식 지표가 증가할수록 세포사 지표는 유의하게 증가하였다(r=0.353, P=0.003). 결론: H. pylori 감염 소아에서 세포 증식 지표와 세포사 지표가 유의하게 증가하였으며 상관성도 유의하였다. 이는 소아에서 위 상피세포 증식과 세포사가 H. pylori의 병인에 중요함을 시사하며, 앞으로 세포 증식과 세포사의 기전, 유발 요인 외에 다른 병독 인자와의 관련성에 대한 연구가 필요하리라 생각된다.

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Corn silk extract improves benign prostatic hyperplasia in experimental rat model

  • Kim, So Ra;Ha, Ae Wha;Choi, Hyun Ji;Kim, Sun Lim;Kang, Hyeon Jung;Kim, Myung Hwan;Kim, Woo Kyoung
    • Nutrition Research and Practice
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    • 제11권5호
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    • pp.373-380
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    • 2017
  • BACKGROUND/OBJECTIVES: This study was conducted to investigate the effect of a corn silk extract on improving benign prostatic hyperplasia (BPH). MATERIALS/METHODS: The experimental animals, 6-week-old male Wistar rats, were divided into sham-operated control (Sham) and experimental groups. The experimental group, which underwent orchiectomy and received subcutaneous injection of 10 mg/kg of testosterone propionate to induce BPH, was divided into a Testo Only group that received only testosterone, a Testo+Fina group that received testosterone and 5 mg/kg finasteride, a Testo+CSE10 group that received testosterone and 10 mg/kg of corn silk extract, and a Testo+CSE100 group that received testosterone and 100 mg/kg of corn silk extract. Prostate weight and concentrations of dihydrotestosterone (DHT), $5{\alpha}$- reductase $2(5{\alpha}-R2)$, and prostate specific antigen (PSA) in serum or prostate tissue were determined. The mRNA expressions of $(5{\alpha}-R2)$ and proliferating cell nuclear antigen (PCNA) in prostate tissue were also measured. RESULTS: Compared to the Sham group, prostate weight was significantly higher in the Testo Only group and decreased significantly in the Testo+Fina, Testo+CSE10, and Testo+CSE100 groups (P < 0.05), results that were consistent with those for serum DHT concentrations. The concentrations of $(5{\alpha}-R2)$ in serum and prostate as well as the mRNA expression of $(5{\alpha}-R2)$ in prostate were significantly lower in the Testo+Fina, Testo+CSE10, and Testo+CSE100 groups than that in the Testo Only group (P < 0.05). Similarly, the concentrations of PSA in serum and prostate were significantly lower in the Testo+Fina, Testo+CSE10, and Testo+CSE100 groups (P < 0.05) than in the Testo Only group. The mRNA expression of PCNA in prostate dose-independently decreased in the Testo+CSE-treated groups (P < 0.05). CONCLUSIONS: BPH was induced through injection of testosterone, and corn silk extract treatment improved BPH symptoms by inhibiting the mRNA expression of $(5{\alpha}-R2)$ and decreasing the amount of $(5{\alpha}-R2)$, DHT, and PSA in serum and prostate tissue.

PMSG 반복투여가 Rat의 과배란에 미치는 영향에 대한 면역조직화학적 연구 2. 투여회수에 따른 정상난포와 퇴축난포의 차이 (Immunohistochemical Study on the Superovulation Effected by Repeat of PMSG Administration in Rats 2. Healthy and Atretic Follicles Following Frequency of PMSG Administrations)

  • 곽수동;고필옥;김종섭
    • 한국가축번식학회지
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    • 제21권3호
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    • pp.265-274
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    • 1997
  • The purpose of this study was attempted to investigate the a, pp.arences of healthy or artretic follicles in ovaries following repeats of pregnant mare serum gonadotropin(PMSG) treatments for superovulation in nulliparous rats. Thirty two rats(Sprague-Dawely, about 200-250 gm) were randomized into 4 groups. Control group rats were sacrified at estrus phase confirmed by vaginal smear. PMSG-treated group 1 rats, PMSG-treated group 2 rats and PMSG-treated group 3 rats were sacrified at 48 hrs after injection once with PMSG 25 IU, after 2 repeated injection by a week interval, and 3 repeated injection, respectively. The ovaires of rats were removed and then sections by paraffin embedding were stained with H-E or immunohistochemical staining using proliferating cell nuclear antigen monoclonal antibody (PCNA m Ab) and apoptotic kit. The criteria of follicle classification was based as small follicles with preantral follicles with 2~4 layers of granulosa cells surrounding the oocyte, as secondary follicles with more than 5 layers of granulosa cells and early signs of antral cavity or with small clefts on either side of the oocytes, and as tirtiary follicles with a single medium sized antral cavity or large well-formed antral cavity, respectively. The proportions of atretic follicles from small and middle follicles in immunohistochemical staining using PCNA m Ab were 17.9% and 21.3% in control group, 15.5% and 23.5% in PMSG-treated group 1, 24.3% and 26.7% in PMSG-treated group 2, 18.1% and 30.2% in PMSG-treated group 3, respectively. Groups with atretic follicles of higher proportion were ordered as PMSG-treated group 3, PMSG-treated group 2, PMSG-treated group 1 and control group. The proportions of positive cells in small, middle and large follicles were 31.1%, 33.5% and 28.5% respectively. The follicles with positive cells of higher proportion were ordered middle, small and large follicles. In immunohischemical staining using apoptotic kits, small follicles in all 4 groups did not contain positive cells, and proportions of atretic follicles from middle and large follicles were 24.9, 30.7, 33.8 and 40.1% in control, PMSG-treated gruop 1, PMSG-treated group 2 and PMSG-treated group 3, respectively. These results suggested that repeats of PMSG treatment increased proportion of atretic follicles in ovaries, and middle follicles are more quickly developing than small or large follicles.

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Overexpression of cholinergic receptor nicotinic gamma subunit inhibits proliferation and differentiation of bovine preadipocytes

  • Jiawei, Du;Hui, Zhao;Guibing, Song;Yuan, Pang;Lei, Jiang;Linsen, Zan;Hongbao, Wang
    • Animal Bioscience
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    • 제36권2호
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    • pp.200-208
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    • 2023
  • Objective: Muscle acetylcholine receptors have five alpha subunits (α, β, δ, ε, or γ), and cholinergic receptor nicotinic gamma subunit (CHRNG) is the γ subunit. It may also play an essential role in biological processes, including cell differentiation, growth, and survival, while the role of CHRNG has not been studied in the literature. Therefore, the purpose of this study is to clarify the effect of CHRNG on the proliferation and differentiation of bovine preadipocytes. Methods: We constructed a CHRNG overexpression adenovirus vector and successfully overexpressed it on bovine preadipocytes. The effects of CHRNG on bovine preadipocyte proliferation were detected by Edu assay, cell counting Kit-8 (CCK-8), real-time fluorescence quantitative polymerase chain reaction (RT-qPCR), Western blot and other techniques. We also performed oil red O, RT-qPCR, Western blot to explore its effect on the differentiation of preadipocytes. Results: The results of Edu proliferation experiments showed that the number of EDU-positive cells in the overexpression group was significantly less. CCK-8 experiments found that the optical density values of the cells in the overexpression group were lower than those of the control group, the mRNA levels of proliferating cell nuclear antigen (PCNA), cyclin A2 (CCNA2), cyclin B1 (CCNB1), cyclin D2 (CCND2) decreased significantly after CHRNG gene overexpression, the mRNA levels of cyclin dependent kinase inhibitor 1A (CDKN1A) increased significantly, and the protein levels of PCNA, CCNB1, CCND2 decreased significantly. Overexpression of CHRNG inhibited the differentiation of bovine preadipocytes. The results of oil red O and triglyceride determination showed that the size and speed of lipid droplets accumulation in the overexpression group were significantly lower. The mRNA and protein levels of peroxisome proliferator activated receptor gamma (PPAR class="checkNonKBPoint">γ), CCAAT enhancer binding protein alpha (CEBPα), fatty acid binding protein 4 (FABP4), fatty acid synthase (FASN) decreased significantly. Conclusion: Overexpression of CHRNG in bovine preadipocytes inhibits the proliferation and differentiation of bovine preadipocytes.

Association between the XRCC1 Arg194Trp Polymorphism and Glioma Risk: an Updated Meta-analysis

  • Xu, Cheng;Chen, Pin;Liu, Wei;Gu, Ai-Hua;Wang, Xin-Ru
    • Asian Pacific Journal of Cancer Prevention
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    • 제15권17호
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    • pp.7419-7424
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    • 2014
  • Gliomas are the most common type of primary brain tumors. The XRCC1 Arg194Trp variant affects the proliferating cell nuclear antigen(PCNA) binding region, which suggests that this mutation may contribute to gliomagenesis and a number of articles have examine the association between XRCC1 Arg194Trp and the susceptibility to glioma. However, the results were conflicting. Test of heterogeneity, sensitivity analysis, meta-analysis, and assessment of publication bias were all performed in our present meta-analysis, covering a total of 5,407 patients and 7,715 healthy persons. In the overall analysis the XRCC1 Arg194Trp polymorphism showed a significant association with glioma susceptibility in a recessive mode l(for TrpTrp vs ArgArg+ArgTrp: OR=1.918, 95%CI=1.575-2.336, $I^2$=2.3%). In addition, analysis of subgroups presented an increased risk in Asians and populations-based on hospitals. The results suggested that the XRCC1 Arg194Trp polymorphism is a genetic risk factor for glioma, especially in Asian population. To further evaluate gene-gene and gene-environment interactions on XRCC1 polymorphisms and glioma risk, thousands of subjects and tissue-specific biochemical characterizations are required.

미성숙 랫드에 있어서 경구 및 피하투여에 의한 Ethinyl estradiol의 자궁증식효과 (Uterotrophic Activity of Ethinyl Estradiol by Gavage and Subcutaneous Administration in Immature Female Rats)

  • 정문구;임광현;김종춘;김영희;서정은;하창수
    • Toxicological Research
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    • 제16권3호
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    • pp.201-209
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    • 2000
  • In association with the international validation program to establish a rodent uterotrophic assay, we conducted preliminary uterotrophic assay proposed by GECD using immature female rats. In the present study, oral and subcutaneous routes were chosen to compare the effects of estrogenic com-pounds in the two dosing regimens. The reference compound ethinyl estradiol (EE) and the antagonist ZM189154(ZM) were administered by gavage or subcutaneously (s.c.) to immature female SD rats from 20 to 22 days of age. For each study, sixty-six female rats were randomly assigned to eleven groups: Untreated control, EE 0,0.01, 0.03, 0.1, 0.3, 1.0,3.0 and 10.0 $\mu\textrm{g}$/kg, EE 3.0 $\mu\textrm{g}$/kg(gavage)/0.3 $\mu\textrm{g}$/kg(s.c) & ZM 0.1 mg/kg, and EE 3.0 $\mu\textrm{g}$/kg(gavage)/0.3 $\mu\textrm{g}$/kg (s.c) & ZM 1.0 mg/kg. There were no treatment-related changes in clinical signs, body weights, food consumption, and necropsy findings in any groups of two studies. The wet and blotted uterus weights increased dose-dependently. Histopathological examination revealed that diameter of uterine duct, height of uterine luminal epithelium. and height oj vaginal epithelium increased dose-dependently. The proliferating cell nuclear antigen (PCNA) immunoreactive cells were increased in number dose-dependently. The estrogenic effects observed in the present studies occurred at $\geq$ 0.3 $\mu\textrm{g}$/kg of oral dose and $\geq$ 0.1 $\mu\textrm{g}$/kg of s.c. dose. An antagonistic effect of ZM against EE was found in both uterus weight and histopathological parameters. From the results obtained, it can be concluded that dose-dependence of the uterotrophic assay using EE and ZM was well demonstrated by gavage and subcutaneous administration and that the estrogenic effects of EE by s.c. dose were higher than those by gavage administration. In addition, blotted uterus weight was more sensitive than wet uterus weight and vaginal epithelial height was found to be the most sensitive parameter among the parameters examined.

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The In Vivo and In Vitro Effects of Terminalia bellirica (Gaertn.) Roxb. Fruit Extract on Testosterone-Induced Hair Loss

  • Min Jeong Woo;Ha Yeong Kang;So Jeong Paik;Hee Jung Choi;Salah Uddin;Sangwoo Lee;Soo-Yong Kim;Sangho Choi;Sung Keun Jung
    • Journal of Microbiology and Biotechnology
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    • 제33권11호
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    • pp.1467-1474
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    • 2023
  • Due to the continuous increase in patients with androgenetic alopecia (AGA) and psychological disorders such as depression and anxiety, the demand for hair loss treatment and effective hair growth materials has increased. Terminalia bellirica (Gaertn.) Roxb. (TBE) reportedly exerts anti-inflammatory, hepatoprotective, and antidiabetic effects, among others, but its effects on testosterone (TS)-inhibited hair growth remains unclear. In this study, we evaluated the effects of TBE on TS-induced hair growth regression in human follicle dermal papilla cells (HFDPCs) and C57BL/6 mice. Oral administration of TBE increased TS-induced hair growth retardation. Interestingly, effects were greater when compared with finasteride, a commercial hair loss treatment product. Histological analyses revealed that oral TBE administration increased hair follicles in the dorsal skin of C57BL/6 mice. Additionally, western blotting and immunofluorescence showed that oral TBE administration recovered the TS-induced inhibition of cyclin D1, proliferating cell nuclear antigen (PCNA), and Ki67 expression in vivo. Using in vitro proliferation assays, TBE promoted HFDPC growth, which was suppressed by TS treatment. Thus, TBE may be a promising nutraceutical for hair health as it promoted hair growth in AGA-like in vitro and in vivo models.

감잎의 광노화 피부 개선에 미치는 효과(1) (Effects of Persimmon leaf on the Photoaging Skin Improvement(1))

  • 이창현;김남석;최동성;오미진;마상용;김명순;유승정;권진;신현종;오찬호
    • 동의생리병리학회지
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    • 제27권6호
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    • pp.771-781
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    • 2013
  • This study was performed to investigate the anti-photoaging effects of Persimmon leaf tea(PLT) in hairless mice(SKH-1) exposed to UVB irradiation. The animals were divided into non-treated group (normal, N) and UV-radiated groups. UV-radiated groups were divided into only UV-radiated group(control, C) and UV-radiated and PLT treated experimental groups[first extraction treated group(PLT-I), second extraction treated group(PLT-II), and third extraction treated group(PLT-III)]. Three PLT treated experimental groups of mice were treated with both oral administration(300 mg/Kg B.W./day) and topical application (100 ul of 2% conc./mouse/day) for 4 weeks. Anti-photoaging effects of Persimmon leaf were evaluated by anti oxidative reaction, stereomicroscopic and microscopic observations. The expression of photoaging skin related factors including mast cell tryptase, proliferating cell nuclear antigen (PCNA) and vascular endothelial growth factor (VEGF) was examined by immunohistochemical staining. Treatment of PLT-I, -II, -III prevented the wrinkle formation as well as epidermal hyperplasia, inflammatory cells, disruption of collagen in photoaged skin induced by UVB radiation. It also reduced the PCNA and VEGF expression in the UVB irradiated dorsal skin. Furthermore, it significantly decreased the number of mast cells in the UVB irradiated dermis(p<0.05 and p<0.01). On the effects of oxidative stress and antioxidant function on the treatment with water extract from Persimmon leaf tea(PLT), the activity of superoxide dismutase(SOD) was significantly increased in PLT-III group(p<0.05), and catalase(CAT) was significantly increased in PLT-I and PLT-III groups(p<0.05), and PLT-II group(p<0.001). These extracts showed relatively antioxidant activity and protective effect on UVB-induced oxidative stress in hairless mice(SKH-1). Our results suggest that Persimmon leaf tea may serve as an useful radical scavenging antioxidant and anti-photoaging skin agents in the UVB irradiated skin.

Maternal Low-protein Diet Alters Ovarian Expression of Folliculogenic and Steroidogenic Genes and Their Regulatory MicroRNAs in Neonatal Piglets

  • Sui, Shiyan;Jia, Yimin;He, Bin;Li, Runsheng;Li, Xian;Cai, Demin;Song, Haogang;Zhang, Rongkui;Zhao, Ruqian
    • Asian-Australasian Journal of Animal Sciences
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    • 제27권12호
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    • pp.1695-1704
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    • 2014
  • Maternal malnutrition during pregnancy may give rise to female offspring with disrupted ovary functions in adult age. Neonatal ovary development predisposes adult ovary function, yet the effect of maternal nutrition on the neonatal ovary has not been described. Therefore, here we show the impact of maternal protein restriction on the expression of folliculogenic and steroidogenic genes, their regulatory microRNAs and promoter DNA methylation in the ovary of neonatal piglets. Sows were fed either standard-protein (SP, 15% crude protein) or low-protein (LP, 7.5% crude protein) diets throughout gestation. Female piglets born to LP sows showed significantly decreased ovary weight relative to body weight (p<0.05) at birth, which was accompanied with an increased serum estradiol level (p<0.05). The LP piglets demonstrated higher ratio of bcl-2 associated X protein/B cell lymphoma/leukemia-2 mRNA (p<0.01), which was associated with up-regulated mRNA expression of bone morphogenic protein 4 (BMP4) (p<0.05) and proliferating cell nuclear antigen (PCNA) (p<0.05). The steroidogenic gene, cytochrome P450 aromatase (CYP19A1) was significantly down-regulated (p<0.05) in LP piglets. The alterations in ovarian gene expression were associated with a significant down-regulation of follicle-stimulating hormone receptor mRNA expression (p<0.05) in LP piglets. Moreover, three microRNAs, including miR-423-5p targeting both CYP19A1 and PCNA, miR-378 targeting CYP19A1 and miR-210 targeting BMP4, were significantly down-regulated (p<0.05) in the ovary of LP piglets. These results suggest that microRNAs are involved in mediating the effect of maternal protein restriction on ovarian function through regulating the expression of folliculogenic and steroidogenic genes in newborn piglets.