• 제목/요약/키워드: Cancer Metabolism

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Redox Regulation of Apoptosis before and after Cytochrome C Release

  • Chen, Quan;Crosby, Meredith;Almasan, Alex
    • Animal cells and systems
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    • 제7권1호
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    • pp.1-9
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    • 2003
  • Programmed cell death, or apoptosis, is one of the most studied areas of modern biology. Apoptosis is a genetically regulated process, which plays an essential role in the development and homeostasis of higher organisms. Mitochondria, known to play a central role in regulating cellular metabolism, was found to be critical for regulating apoptosis induced under both physiological and pathological conditions. Mitochondria are a major source of reactive oxygen species (ROS) but they can also serve as its target during the apoptosis process. Release of apoptogenic factors from mitochondria, the best known of which is cytochrome c, leads to assembly of a large apoptosis-inducing complex called the apoptosome. Cysteine pretenses (called caspases) are recruited to this complex and, following their activation by proteolytic cleavage, activate other caspases, which in turn target for specific cleavage a large number of cellular proteins. The redox regulation of apoptosis during and after cytochrome c release is an area of intense investigation. This review summarizes what is known about the biological role of ROS and its targets in apoptosis with an emphasis on its intricate connections to mitochondria and the basic components of cell death.

Anti-inflammatory effects of Agar free-Gelidium amansii (GA) extracts in high-fat diet-induced obese mice

  • Lee, Yunkyoung;Oh, Hyunhee;Lee, Myoungsook
    • Nutrition Research and Practice
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    • 제12권6호
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    • pp.479-485
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    • 2018
  • BACKGROUND/OBJECTIVES: Gelidium amansii (GA) contains plenty of agars and various biological substances, which make them a popular functional food to control body weight in previous studies. Unlike previous studies focused on agar in GA, objectives of this study were to investigate the effects of agar-free GA extract (AfGAE) on preventive and treatment models by using diets-induced obese (DIO) C57BL/6J mice. MATERIALS/METHODS: AfGAE were used to test their effects on the prevention (Exp-1) and treatment (Exp-2) against obesity after pilot study in DIO mice. The weight changes of the body and fat tissues and protein expression related to lipid metabolism and inflammation as well as plasma lipid profile and insulin were detected. RESULTS: Although AfGAE did not prevent long-term DIO, it did increase the levels of anti-inflammatory cytokine production and lipolysis protein. We further evaluated various doses of AfGAE in preventive and treatment models. As a result, our findings suggested that an AfGAE administration as a preventive model might be a better approach to achieve its anti-inflammatory and lipolysis-promoting effects in DIO mice. CONCLUSION: Although future studies to investigate the target materials such as polyphenols in AfGAE are required, the result suggests that GA without agar might be a therapeutic tool to improve health conditions related to inflammation.

Emerging roles of PHLPP phosphatases in metabolism

  • Cha, Jong-Ho;Jeong, Yelin;Oh, Ah-Reum;Lee, Sang Bae;Hong, Soon-Sun;Kim, KyeongJin
    • BMB Reports
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    • 제54권9호
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    • pp.451-457
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    • 2021
  • Over the last decades, research has focused on the role of pleckstrin homology (PH) domain leucine-rich repeat protein phosphatases (PHLPPs) in regulating cellular signaling via PI3K/Akt inhibition. The PKB/Akt signaling imbalances are associated with a variety of illnesses, including various types of cancer, inflammatory response, insulin resistance, and diabetes, demonstrating the relevance of PHLPPs in the prevention of diseases. Furthermore, identification of novel substrates of PHLPPs unveils their role as a critical mediator in various cellular processes. Recently, researchers have explored the increasing complexity of signaling networks involving PHLPPs whereby relevant information of PHLPPs in metabolic diseases was obtained. In this review, we discuss the current knowledge of PHLPPs on the well-known substrates and metabolic regulation, especially in liver, pancreatic beta cell, adipose tissue, and skeletal muscle in relation with the stated diseases. Understanding the context-dependent functions of PHLPPs can lead to a promising treatment strategy for several kinds of metabolic diseases.

비만환자의 만성콩팥병 관리 (Management of Chronic Kidney Disease in Obesity Patients)

  • 한건희
    • 비만대사연구학술지
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    • 제1권2호
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    • pp.66-73
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    • 2022
  • Obesity is an increasing public health and medical issue worldwide. It has been associated with several comorbidities, including diabetes, cardiovascular disease, stroke, and cancer. Chronic kidney disease (CKD) is another important comorbidity of obesity. Other major causes of CKD include hypertension and diabetes. However, the association between obesity and CKD is often overlooked. Among patients with CKD, patients with obesity were more vulnerable to have rapid kidney function decline than that of those with normal weight. Additionally, CKD is more prevalent among patients with obesity. These aggravations are induced through multiple mechanisms, specifically metabolic impairment of obesity and mechanical burden because of increasing intraabdominal renal pressure. Furthermore, the inflammation and lipotoxicity, caused by obesity, are critical in the CKD aggravation in patients with obesity. To prevent this, all adult patients with obesity are tested for CKD. The workup includes the estimated glomerular filtration rate and regular follow-up. Step-wise management is required for patients with obesity with CKD. Prompt reduction and management of obesity effectively delay CKD progression among patients with obesity and CKD. Therefore, weight loss is a core management for patients with obesity and CKD. Based on several studies, this article focused on the association between CKD and obesity, as well as the diagnosis and weight management of patients with obesity and CKD.

Autophagy inhibition by cudraxanthone D regulates epithelial-mesenchymal transition in SCC25 cells

  • Yu, Su-Bin;Bang, Tae-Hyun;Kang, Hae-Mi;Park, Bong-Soo;Kim, In-Ryoung
    • International Journal of Oral Biology
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    • 제46권1호
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    • pp.30-38
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    • 2021
  • Cudraxanthone D (CD) is a natural xanthone compound derived from the root barks of Cudrania tricuspidata. However, the biological functions of CD in human metabolism have been rarely reported until now. Autophagy is the self-degradation process related to cancer cell metastasis. Here, we elucidated the effects of CD on human oral squamous cell carcinoma (OSCC) cells' metastatic ability. We confirmed that CD effectively decreased the proliferation and viability of SCC25 human OSCC cells in time- and dose-dependent manners. Also, the metastasis phenotype of the SCC25 cell (migration, invasion, and epithelial-mesenchymal transition [EMT]) was inhibited by CD. To further investigate the mechanism by which CD inhibited the metastatic capacity, we detected the relationship between EMT and autophagy in the SCC25 cells. The results revealed that CD inhibited the metastasis of the SCC25 cells by attenuating autophagy. Thus, our findings produced a potential novel agent for the treatment of human OSCC metastasis.

Comparative proteomic analysis of Celastrus hindsii Benth. phenotypes reveals an intraspecific variation

  • Nguyen, Van Huy;Pham, Thanh Loan;Ha, Thi Tam Tien;Hoang, Thi Le Thu
    • Journal of Plant Biotechnology
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    • 제47권4호
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    • pp.273-282
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    • 2020
  • In Vietnam, Celastrus hindsii Benth, a medicinal plant rich in secondary metabolites, has been used to alleviate distress caused by ulcers, tumors, and inflammation for generations. The occurrence of two phenotypes, Broad Leaf (BL) and Narrow Leaf (NL), has raised questions about the selection of appropriate varieties for conservation and crop improvement to enhance medicinal properties. This study examined molecular differences in C. hindsii by comparing protein profiles between the NL and BL types using 2D-PAGE and MS. Peptide sequences and proteins were identified by matching MS data against the MSPnr100 databases and verified using the MultiIdent tool on ExPASy and the Blast2GO software. Our results revealed notable variations in protein abundance between the NL and BL proteomes. Selected proteins were confidently identified from 12 protein spots, thereby highlighting the molecular variation between NL and BL proteomes. Upregulated proteins in BL were found to be associated with flavonoid and amino acid biosynthesis as well as nuclease metabolism, which probably attributed to the intraspecific variations. Several bioactive proteins identified in this study can have applications in cancer therapeutics. Therefore, the BL phenotype characterized by healthier external morphological features has higher levels of bioactive compounds and could be better suited for medicinal use.

Anti-Ferroptotic Effects of Nrf2: Beyond the Antioxidant Response

  • Aryatara Shakya;Nicholas W. McKee;Matthew Dodson;Eli Chapman;Donna D. Zhang
    • Molecules and Cells
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    • 제46권3호
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    • pp.165-175
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    • 2023
  • The transcription factor Nrf2 was originally identified as a master regulator of redox homeostasis, as it governs the expression of a battery of genes involved in mitigating oxidative and electrophilic stress. However, the central role of Nrf2 in dictating multiple facets of the cellular stress response has defined the Nrf2 pathway as a general mediator of cell survival. Recent studies have indicated that Nrf2 regulates the expression of genes controlling ferroptosis, an iron-and lipid peroxidation-dependent form of cell death. While Nrf2 was initially thought to have anti-ferroptotic function primarily through regulation of the antioxidant response, accumulating evidence has indicated that Nrf2 also exerts anti-ferroptotic effects via regulation of key aspects of iron and lipid metabolism. In this review, we will explore the emerging role of Nrf2 in mediating iron homeostasis and lipid peroxidation, where several Nrf2 target genes have been identified that encode critical proteins involved in these pathways. A better understanding of the mechanistic relationship between Nrf2 and ferroptosis, including how genetic and/or pharmacological manipulation of Nrf2 affect the ferroptotic response, should facilitate the development of new therapies that can be used to treat ferroptosis-associated diseases.

Investigating the Potential of Lipids for Use as Biomarkers for Glioblastoma via an Untargeted Lipidomics Approach

  • Burcak Soylemez;Zekeriya Bulut;Serap Sahin-Bolukbasi
    • Journal of Korean Neurosurgical Society
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    • 제66권2호
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    • pp.133-143
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    • 2023
  • Objective : The types and functions of lipids involved in glioblastoma (GB) are not well known. Lipidomics is a new field that examines cellular lipids on a large scale and novel aplication of lipidomics in the biomedical sciences have emerged. This study aimed to investigate the potential of blood lipids for use as biomarkers for the diagnosis of GB via untargated lipidomic approach. Gaining a deeper understanding of lipid metabolism in patients with GB can contribute to the early diagnosis with GB patiens and also development of novel and better therapeutic options. Methods : This study was performed using blood samples collected from 14 patients (eight females and six males) and 14 controls (eight females and six males). Lipids were extracted from blood samples and quantified using phosphorus assay. Lipid profiles of between patients with GB and controls were compared via an untargeted lipidomics approach using 6530 Accurate-Mass Q-TOF LC/MS mass spectrometer. Results : According to the results obtained using the untargeted lipidomics approach, differentially regulated lipid species, including fatty acid (FA), glycerolipid (GL), glycerophospholipid (PG), saccharolipid (SL), sphingolipid (SP), and sterol lipid (ST) were identified between in patients with GB and controls. Conclusion : Differentially regulated lipids were identified in patients with GB, and these lipid species were predicted as potential biomarkers for diagnosis of GB.

Alleviation of imiquimod-induced psoriasis-like symptoms in Rorα-deficient mouse skin

  • Koog Chan Park;Jiwon Kim;Aram Lee;Jong-Seok Lim;Keun Il Kim
    • BMB Reports
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    • 제56권5호
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    • pp.296-301
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    • 2023
  • Retinoic acid receptor-related orphan receptor α (RORα) plays a vital role in various physiological processes, including metabolism, cancer, circadian rhythm, cerebellar development, and inflammation. Although RORα is expressed in the skin, its role in skin physiology remains poorly elucidated. Herein, Rorα was expressed in the basal and suprabasal layers of the epidermis; however, keratinocyte-specific Rorα deletion did not impact normal epidermal formation. Under pathophysiological conditions, Rorα-deficient mice exhibited alleviated psoriasis-like symptoms, including relatively intact epidermal stratification, reduced keratinocyte hyperproliferation, and low-level expression of inflammatory cytokines in keratinocytes. Unexpectedly, the splenic population of Th17 cells was significantly lower in keratinocyte-specific RORα deficient mice than in the control. Additionally, Rorα-deficiency reduced imiquimod-induced activation of nuclear factor-κB and STAT3 in keratinocytes. Therefore, we expect that RORα inhibitors act on immune cells and keratinocytes to suppress the onset and progression of psoriasis.

지방육종형성 동물모델에서 $^{123}I$-15-(p-iodophenyl)-3-R, S-methylpentadecanoic acid (BMIPP)의 생체분포와 생체영상 (In Vivo Image and Biodistribution of $^{123}I$-15-(p-iodophenyl)-3-R, S-methylpentadecanoic acid (BMIPP) in Liposarcoma Bearing Nude Mice)

  • 이태섭;서용섭;최창운;우광선;정위섭;임수정;임상무;오옥두
    • 대한핵의학회지
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    • 제35권5호
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    • pp.324-333
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    • 2001
  • 목적: $^{123}I$ 표지된 지방산 유도체는 심근에너지대사를 평가하는데 사용되어 왔다. 본 연구는 $^{123}I$-BMIPP를 지방육종 진단물질로서의 유용성을 평가하기 위하여, 지방육종 세포주와 신경교종 세포주간의 시험관내의 섭취율을 비교하고 지방육종 형성 nude mice 동물모델에서의 생체분포와 생체영상을 확인하였다. 대상 및 방법: Cold-BMIPP에 $^{123}I$의 표지는 $Cu^{2+}$를 촉매로 이용하여 반응 후 Sep-pak으로 분리정제하여 TLC를 이용하여 방사화학적 순도를 확인하였다. 시험관내 섭취율 시험은 $^{123}I$-BMIPP를 지방육종 세포주인 SW872와 신경교종 세포주인 9L에 각각 시간대별로 5분, 15분, 30분, 60분, 120분, 180분씩 처리한 후 섭취율을 비교하였다. 정상 백서에서의 생체분포를 평가하기 위하여 18시간 금식시킨 군(n=6/군)과 식이를 한 군으로하여 $^{123}I$-BMIPP를 꼬리정맥에 주사하고 30분, 2시간, 24시간후의 각 장기별 방사능을 감마카운터로 계측하였다. 지방육종 세포주인 SW872를 왼쪽 대퇴부에 피하접종한후 종양이 형성된 누드마우스(n=5/군)를 18시간 금식시키고 $^{123}I$-BMIPP를 주사한 후 30분, 2시간, 24시간후의 생체분포와 2시간, 24시간의 생체영상을 평가하였다. 결과: $^{123}I$-BMIPP의 표지수율은 95 % 이상이었으며, 방사화학적 순도는 99 % 이상이었다. 지방육종 세포주인 SW872가 신경교종 세포주인 9L보다 180분에서 1.5배 정도의 섭취율의 증가를 나타내었다. 정상 백서에서의 생체분포를 확인한 결과, 24시간에서 금식을 한 경우가 식이를 한 경우보다 방사성표지 지방산의 제거율이 지연됨을 알 수가 있었으며 주요 배출장기는 위장관으로 확인되었다. 지방육종이 형성된 누드마우스에서 각 시간대별로 Tumor/Blood 비율은 0.94, 0.75, 1.38이었고, Tumor/Muscle의 비율은 0.66, 1.53, 1.11을 나타내었다. 24시간의 감마카메라영상에서 지방육종으로의 국소적인 집적이 확인되었다. 결론: 이상의 결과를 종합해볼 때 지방육종에서 $^{123}I$-BMIPP를 지방육종 영상물질로서의 사용 가능성을 확인할 수 있었다.

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