• 제목/요약/키워드: secretory pathway

검색결과 56건 처리시간 0.026초

자궁근종에서 타목시펜의 수용체를 통한 기전 (The Action Mechanism of Tamoxifen Via Estrogen Receptor on Uterine Leimyoma)

  • 이병석;차동현;정경아;이희대;박기현;조동제;송찬호
    • Clinical and Experimental Reproductive Medicine
    • /
    • 제29권4호
    • /
    • pp.337-343
    • /
    • 2002
  • Objectives: To investigate the distribution of $ER{\alpha}$, $ER{\beta}$, c-fos and c-jun in the uterine myoma and myometrium in oder to know how the tamoxifen cause the growth of myoma. Methods: Myoma and myometrial tissue were obtained from the postmenopausal women treated with tamoxifen in the patients with breast cancer and in the premenopausal patients, who were undergoing myoma of uterus from 1998 through 2000. The espression of each gene was quantitated with quantitative RT-PCR. Results: The expression of $ER{\alpha}$ was slightly increased in the myoma than the myometrium in the proliferative phase, and was slightly decreased in the myometrium than the myoma in the secretory phase. However it was not significant statistically. In the postmemopausal women treated with tamoxifen, $ER{\alpha}$ was expressed in all myoma and myome1rial tissues and the expression was not statistically significant. The expression ofER~ was slightly increased in the myome1rium than the leiomyoma in the proliferative and secretory phase, but it was not significant statistically. In the postmemopausal women treated with tamoxifen, the expression of ER~ was significantly incresed in the myome1rium than the leiomyoma. The expression of c-fos was significantly increased in the myome1rium than the leiomyoma in the proliferative and secretory phase. In the postmemopausal women treated with tamoxifen, the expression of c-fos was slightly increased in the leiomyoma than the myomelrium, however, it was not statistically significant. Conclusion: Tamoxifen may cause the growth of leiomyoma by $ER{\alpha}$ with AP-l pathway reducing the counteraction of 6$ER{\beta}$ to $ER{\alpha}$.

Valeriana jatamansi Jones Inhibits Rotavirus-Induced Diarrhea via Phosphatidylinositol 3-Kinase/Protein Kinase B Signaling Pathway

  • Zhang, Bin;Wang, Yan;Jiang, Chunmao;Wu, Caihong;Guo, Guangfu;Chen, Xiaolan;Qiu, Shulei
    • Journal of Microbiology and Biotechnology
    • /
    • 제31권8호
    • /
    • pp.1115-1122
    • /
    • 2021
  • Rotavirus (RV), as the main cause of diarrhea in children under 5 years, contributes to various childhood diseases. Valeriana jatamansi Jones is a traditional Chinese herb and possesses antiviral effects. In this study we investigated the potential mechanisms of V. jatamansi Jones in RV-induced diarrhea. MTT assay was performed to evaluate cell proliferation and the diarrhea mice model was constructed using SA11 infection. Mice were administered V. jatamansi Jones and ribavirin. Diarrhea score was used to evaluate the treatment effect. The enzyme-linked immunosorbent assay was performed to detect the level of cytokines. Western blot and quantitative reverse transcription-PCR were used to determine protein and mRNA levels, respectively. Hematoxylin-eosin staining was applied to detect the pathological change of the small intestine. TdT-mediated dUTP nick-end labeling was conducted to determine the apoptosis rate. The results showed V. jatamansi Jones promoted MA104 proliferation. V. jatamansi Jones downregulated phosphatidylinositol 3-kinase (PI3K) and protein kinase B (AKT) in protein level, which was consistent with the immunohistochemistry results. Moreover, V. jatamansi Jones combined with ribavirin regulated interleukin-1β (IL-1β), interferon γ, IL-6, tumor necrosis factor α, and IL-10, and suppressed secretory immunoglobulin A secretion to remove viruses and inhibit dehydration. V. jatamansi Jones + ribavirin facilitated the apoptosis of small intestine cells. In conclusion, V. jatamansi Jones may inhibit RV-induced diarrhea through PI3K/AKT signaling pathway, and could therefore be a potential therapy for diarrhea.

The ADAM15 ectodomain is shed from secretory exosomes

  • Lee, Hee Doo;Kim, Yeon Hyang;Koo, Bon-Hun;Kim, Doo-Sik
    • BMB Reports
    • /
    • 제48권5호
    • /
    • pp.277-282
    • /
    • 2015
  • We demonstrated previously that a disintegrin and metalloproteinase 15 (ADAM15) is released into the extracellular space as an exosomal component, and that ADAM15-rich exosomes have tumor suppressive functions. However, the suppressive mechanism of ADAM15-rich exosomes remains unclear. In this study, we show that the ADAM15 ectodomain is cleaved from released exosomes. This shedding process of the ADAM15 ectodomain was dramatically enhanced in conditioned ovarian cancer cell medium. Proteolytic cleavage was completely blocked by phenylmethylsulfonyl fluoride, indicating that a serine protease is responsible for exosomal ADAM15 shedding. Experimental evidence indicates that the ADAM15 ectodomain itself has comparable functions with those of ADAM15-rich exosomes, which effectively inhibit vitronectininduced cancer cell migration and activation of the MEK/extracellular regulated kinase signaling pathway. We present a tumor suppressive mechanism for ADAM15 exosomes and provide insight into the functional significance of exosomes that generate tumor-inhibitory factors. [BMB Reports 2015; 48(5): 277-282]

Delayed Human Neutrophil Apoptosis by Trichomonas vaginalis Lysate

  • Song, Hyun-Ouk;Lim, Young-Su;Moon, Sun-Joo;Ahn, Myoung-Hee;Ryu, Jae-Sook
    • Parasites, Hosts and Diseases
    • /
    • 제48권1호
    • /
    • pp.1-7
    • /
    • 2010
  • Neutrophils play an important role in the human immune system for protection against such microorganisms as a protozoan parasite, Trichomonas vaginalis; however, the precise role of neutrophils in the pathogenesis of trichomoniasis is still unknown. Moreover, it is thought that trichomonal lysates and excretory-secretory products (ESP), as well as live T. vaginalis, could possibly interact with neutrophils in local tissues, including areas of inflammation induced by T. vaginalis in humans. The aim of this study was to investigate the influence of T. vaginalis lysate on the fate of neutrophils. We found that T. vaginalis lysate inhibits apoptosis of human neutrophils as revealed by Giemsa stain. Less altered mitochondrial membrane potential (MMP) and surface CD16 receptor expression also supported the idea that neutrophil apoptosis is delayed after T. vaginalis lysate stimulation. In contrast, ESP stimulated-neutrophils were similar in apoptotic features of untreated neutrophils. Maintained caspase-3 and myeloid cell leukemia-1 (Mcl-1) in neutrophils co-cultured with trichomonad lysate suggest that an intrinsic mitochondrial pathway of apoptosis was involved in T. vaginalis lysate-induced delayed neutrophil apoptosis; this phenomenon may contribute to local inflammation in trichomoniasis.

Intracellular Responses of Antibody-Producing H69K-NGD Transfectoma Subjected to Hyperosmotic Pressure

  • Bae, Sung-Won;Lee, Gyun-Min
    • Journal of Microbiology and Biotechnology
    • /
    • 제15권3호
    • /
    • pp.579-586
    • /
    • 2005
  • When subjected to hyperosmotic pressure by NaCl addition, H69K-NGD transfectoma, like KR12H-2 transfectoma, displayed decreased specific growth rate (${\mu}$) and increased specific antibody productivity ($q_{Ab}$): Elevation of medium osmolality from 280 mOsm/kg to 415 mOsm/kg decreased ${\mu}$ by $79\%$ in batch cultures of H69K-NGD transfectoma, while it increased $q_{Ab}$ by $103\%$. However, unlike KR12H-2 tranfectoma, enhanced $q_{Ab}$ of H69K-NGD transfectoma at hyperosmolalities was not due to elevated levels of Ig mRNAs. In hyperosmotic cultures of H69K-NGD transfectoma, heavy-chain mRNA per cell was not enhanced with increasing osmolality. Hyperosmotic pressure was found to preferentially enhance immunoglobulin (Ig) translation rates of H69K-NGD transfectoma. However, under hyperosmotic pressure, the translation rate of Ig polypeptides was not enhanced as much as $q_{Ab}$. This result suggests that hyperosmotic pressure also influences the post-translational process. Taken together, the results obtained show that intracellular response of transfectomas to hyperosmotic pressure, in regard to the main intracellular steps of the antibody secretory pathway, is cell-line dependent.

Hypothetical protein predicted to be tumor suppressor: a protein functional analysis

  • Kader, Md. Abdul;Ahammed, Akash;Khan, Md. Sharif;Ashik, Sheikh Abdullah Al;Islam, Md. Shariful;Hossain, Mohammad Uzzal
    • Genomics & Informatics
    • /
    • 제20권1호
    • /
    • pp.6.1-6.15
    • /
    • 2022
  • Litorilituus sediminis is a Gram-negative, aerobic, novel bacterium under the family of Colwelliaceae, has a stunning hypothetical protein containing domain called von Hippel-Lindau that has significant tumor suppressor activity. Therefore, this study was designed to elucidate the structure and function of the biologically important hypothetical protein EMK97_00595 (QBG34344.1) using several bioinformatics tools. The functional annotation exposed that the hypothetical protein is an extracellular secretory soluble signal peptide and contains the von Hippel-Lindau (VHL; VHL beta) domain that has a significant role in tumor suppression. This domain is conserved throughout evolution, as its homologs are available in various types of the organism like mammals, insects, and nematode. The gene product of VHL has a critical regulatory activity in the ubiquitous oxygen-sensing pathway. This domain has a significant role in inhibiting cell proliferation, angiogenesis progression, kidney cancer, breast cancer, and colon cancer. At last, the current study depicts that the annotated hypothetical protein is linked with tumor suppressor activity which might be of great interest to future research in the higher organism.

Analyzing the factors that contribute to the development of embryological classical type of bladder exstrophy

  • Ria Margiana;Widya Juwita;Khoirul Ima;Zakiyatul Faizah;Supardi Supardi
    • Anatomy and Cell Biology
    • /
    • 제56권4호
    • /
    • pp.421-427
    • /
    • 2023
  • Bladder exstrophy is a rare congenital condition of the pelvis, bladder, and lower abdomen that opens the bladder against the abdominal wall, produces aberrant growth, short penis, upward curvature during erection, wide penis, and undescended testes. Exstrophy affects 1/30,000 newborns. The bladder opens against the abdominal wall in bladder exstrophy, a rare genitourinary condition. This study is vital to provide appropriate therapy choices as a basis to improve patient outcomes. This study may explain bladder exstrophy and provide treatment. Epispadias, secretory placenta, cloacal exstrophy, and other embryonic abnormalities comprise the exstrophy-spades complex. The mesenchymal layer does not migrate from the ectoderm and endoderm layers in the first trimester, affecting the cloacal membrane. Embryological problems define the exstrophy-aspidistra complex, which resembles epimedium, classic bladder, cloacal exstrophy, and other diseases. Urogenital ventral body wall anomalies expose the bladder mucosa, causing bladder exstrophy. Genetic mutations in the Hedgehog cascade pathway, Wnt signal, FGF, BMP4, Alx4, Gli3, and ISL1 cause ventral body wall closure and urinary bladder failure. External factors such as high maternal age, smoking moms, and high maternal body mass index have also been associated to bladder exstrophy. Valproic acid increases bladder exstrophy risk; chemicals and pollutants during pregnancy may increase bladder exstrophy risk. Bladder exstrophy has no identified cause despite these risk factors. Exstrophy reconstruction seals the bladder, improves bowel function, reconstructs the vaginal region, and restores urination.

SARS-CoV-2 Infection of Airway Epithelial Cells

  • Gwanghui Ryu;Hyun-Woo Shin
    • IMMUNE NETWORK
    • /
    • 제21권1호
    • /
    • pp.3.1-3.16
    • /
    • 2021
  • Coronavirus disease 2019 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been spreading worldwide since its outbreak in December 2019, and World Health Organization declared it as a pandemic on March 11, 2020. SARS-CoV-2 is highly contagious and is transmitted through airway epithelial cells as the first gateway. SARS-CoV-2 is detected by nasopharyngeal or oropharyngeal swab samples, and the viral load is significantly high in the upper respiratory tract. The host cellular receptors in airway epithelial cells, including angiotensin-converting enzyme 2 and transmembrane serine protease 2, have been identified by single-cell RNA sequencing or immunostaining. The expression levels of these molecules vary by type, function, and location of airway epithelial cells, such as ciliated cells, secretory cells, olfactory epithelial cells, and alveolar epithelial cells, as well as differ from host to host depending on age, sex, or comorbid diseases. Infected airway epithelial cells by SARS-CoV-2 in ex vivo experiments produce chemokines and cytokines to recruit inflammatory cells to target organs. Same as other viral infections, IFN signaling is a critical pathway for host defense. Various studies are underway to confirm the pathophysiological mechanisms of SARS-CoV-2 infection. Herein, we review cellular entry, host-viral interactions, immune responses to SARS-CoV-2 in airway epithelial cells. We also discuss therapeutic options related to epithelial immune reactions to SARS-CoV-2.

Age-related Autoimmune Changes in Lacrimal Glands

  • Rodrigo G. de Souza;Cintia S. de Paiva;Milton R. Alves
    • IMMUNE NETWORK
    • /
    • 제19권1호
    • /
    • pp.3.1-3.17
    • /
    • 2019
  • Aging is a complex process associated with dysregulation of the immune system and low levels of inflammation, often associated with the onset of many pathologies. The lacrimal gland (LG) plays a vital role in the maintenance of ocular physiology and changes related to aging directly affect eye diseases. The dysregulation of the immune system in aging leads to quantitative and qualitative changes in antibodies and cytokines. While there is a gradual decline of the immune system, there is an increase in autoimmunity, with a reciprocal pathway between low levels of inflammation and aging mechanisms. Elderly C57BL/6J mice spontaneously show LGs infiltration that is characterized by Th1 but not Th17 cells. The aging of the LG is related to functional alterations, reduced innervation and decreased secretory activities. Lymphocytic infiltration, destruction, and atrophy of glandular parenchyma, ductal dilatation, and secretion of inflammatory mediators modify the volume and composition of tears. Oxidative stress, the capacity to metabolize and eliminate toxic substances decreased in aging, is also associated with the reduction of LG functionality and the pathogenesis of autoimmune diseases. Although further studies are required for a better understanding of autoimmunity and aging of the LG, we described anatomic and immunology aspects that have been described so far.

소포체스트레스 센서 OASIS family의 분자기전 (Molecular Mechanism of Endoplasmic Reticulum Stress Transducer OASIS Family)

  • 권기상;김승환;유권;권오유
    • 생명과학회지
    • /
    • 제25권4호
    • /
    • pp.473-480
    • /
    • 2015
  • 진핵세포의 소포체는 분비를 담당하는 첫 번째 기관이다. 대부분의 분비단백질과 막 형성단백질은 소포체에서 세포질/핵으로 전달되는 신호전달에 의한 번역후수식에 의해서 소포체를 통해서 분비된다. 그 결과 완전하게 접 힘이 일어난 단백질만 세포 밖으로 분비된다. 소포체내에서 완전하게 접힘이 일어나지 않아 축적된 단백질은 세 포내스트레스(소포체스트레스)가 되어 unfolded protein response (UPR)시스템을 작동시킨다. UPR을 작동시키는 3종류의 소포체막단백질은 inositol requiring 1 (IRE1), PKR-like ER kinase (PERK), activating transcription factor 6 (ATF6)이 존재한다. 최근에 새로운 종류의 ATF6이 동정되었다. 이들은(Luman, OASIS, BBF2H7, CREBH, CREB4) 공통적으로 소포체막관통영역, 전사활성영역, bZIP영역을 가지며 특이조직과 세포내기관에서 기능을 가 진다. 현재로서는 OASIS family의 정확한 분자기전 설명은 어렵지만, 본 리뷰에서 이들 분자신호를 포괄적으로 소개할 것이다