The aim of the present study was to evaluate the effects of two well-known natural antioxidants, vitamin C (VC) and vitamin E (VE), on the antifungal activity of honokiol against Candida albicans. The broth microdilution method was employed to test the antifungal activities of honokiol with or without antioxidants in the medium against C. albicans strain. Intracellular reactive oxygen species and lipid peroxidation were determined by fluorescence staining assay. Mitochondrial dysfunction was assessed by detecting the mitochondrial DNA and the mitochondrial membrane potential. We observed that VC could significantly potentiate the antifungal activities of honokiol while VE reduced the effectiveness of honokiol against C. albicans. In addition, VC accelerated honokiol-induced mitochondrial dysfunction and inhibited glycolysis leading to a decrease in cellular ATP. However, VE could protect against mitochondrial membrane lipid peroxidation and rescue mitochondrial function after honokiol treatment. Our research provides new insight into the understanding of the action mechanism of honokiol and VC combination against C. albicans.
Ma, Chaobing;Zu, Xueyin;Liu, Kangdong;Bode, Ann M.;Dong, Zigang;Liu, Zhenzhen;Kim, Dong Joon
Molecules and Cells
/
v.42
no.9
/
pp.628-636
/
2019
Altered genetic features in cancer cells lead to a high rate of aerobic glycolysis and metabolic reprogramming that is essential for increased cancer cell viability and rapid proliferation. Pyruvate kinase muscle (PKM) is a rate-limiting enzyme in the final step of glycolysis. Herein, we report that PKM is a potential therapeutic target in triple-negative breast cancer (TNBC) cells. We found that PKM1 or PKM2 is highly expressed in TNBC tissues or cells. Knockdown of PKM significantly suppressed cell proliferation and migration, and strongly reduced S phase and induced G2 phase cell cycle arrest by reducing phosphorylation of the CDC2 protein in TNBC cells. Additionally, knockdown of PKM significantly suppressed $NF-{\kappa}B$ (nuclear factor kappa-light-chain-enhancer of activated B cells) activity by reducing the phosphorylation of p65 at serine 536, and also decreased the expression of $NF-{\kappa}B$ target genes. Taken together, PKM is a potential target that may have therapeutic implications for TNBC cells.
Aspartate-glutamate carrier 2 (AGC2, citrin) is a mitochondrial carrier expressed in the liver that transports aspartate from mitochondria into the cytosol in exchange for glutamate. The AGC2 is the main component of the malate-aspartate shuttle (MAS) that ensures indirect transport of NADH produced in the cytosol during glycolysis, lactate oxidation to pyruvate, and ethanol oxidation to acetaldehyde into mitochondria. Through MAS, AGC2 is necessary to maintain intracellular redox balance, mitochondrial respiration, and ATP synthesis. Through elevated cytosolic Ca2+ level, the AGC2 is stimulated by catecholamines and glucagon during starvation, exercise, and muscle wasting disorders. In these conditions, AGC2 increases aspartate input to the urea cycle, where aspartate is a source of one of two nitrogen atoms in the urea molecule (the other is ammonia), and a substrate for the synthesis of fumarate that is gradually converted to oxaloacetate, the starting substrate for gluconeogenesis. Furthermore, aspartate is a substrate for the synthesis of asparagine, nucleotides, and proteins. It is concluded that AGC2 plays a fundamental role in the compartmentalization of aspartate and glutamate metabolism and linkage of the reactions of MAS, glycolysis, gluconeogenesis, amino acid catabolism, urea cycle, protein synthesis, and cell proliferation. Targeting of AGC genes may represent a new therapeutic strategy to fight cancer.
Most cancer cells utilize glucose at a high rate to produce energy and precursors for the biosynthesis of macromolecules such as lipids, proteins, and nucleic acids. This phenomenon is called the Warburg effect or aerobic glycolysis- this distinct characteristic is an attractive target for developing anticancer drugs. Here, we found that Phosphofructokinase-1 (PFK-1) is a substrate of the Protein Phosphatase 4 catalytic subunit (PP4C)/PP4 regulatory subunit 1 (PP4R1) complex by using immunoprecipitation and in vitro assay. While manipulation of PP4C/PP4R1 does not have a critical impact on PFK-1 expression, the absence of the PP4C/PP4R1 complex increases PFK-1 activity. Although PP4C depletion or overexpression does not cause a dramatic change in the overall glycolytic rate, PP4R1 depletion induces a considerable increase in both basal and compensatory glycolytic rates, as well as the oxygen consumption rate, indicating oxidative phosphorylation. Collectively, the PP4C/PP4R1 complex regulates PFK-1 activity by reversing its phosphorylation and is a promising candidate for treating glycolytic disorders and cancers. Targeting PP4R1 could be a more efficient and safer strategy to avoid pleiotropic effects than targeting PP4C directly.
Background: Atelectasis is an important prognostic factor that can cause pleuritic chest pain, coughing or dyspnea, and even may be a cause of death. In this study, we aimed to investigate the potential impact of atelectasis and PET parameters on survival and the relation between atelectasis and PET parameters. Materials and Methods: The study consisted of patients with lung cancer with or without atelectasis who underwent $^{18}F$-FDG PET/CT examination before receiving any treatment. $^{18}F$-FDG PET/CT derived parameters including tumor size, SUVmax, SUVmean, MTV, total lesion glycosis (TLG), SUV mean of atelectasis area, atelectasis volume, and histological and TNM stage were considered as potential prognostic factors for overall survival. Results: Fifty consecutive lung cancer patients (22 patients with atelectasis and 28 patients without atelectasis, median age of 65 years) were evaluated in the present study. There was no relationship between tumor size and presence or absence of atelectasis, nor between presence/absence of atelectasis and TLG of primary tumors. The overall one-year survival rate was 83% and median survival was 20 months (n=22) in the presence of atelectasis; the overall one-year survival rate was 65.7% (n=28) and median survival was 16 months (p=0.138) in the absence of atelectasis. With respect to PFS; the one-year survival rate of AT+ patients was 81.8% and median survival was 19 months; the one-year survival rate of AT-patients was 64.3% and median survival was 16 months (p=0.159). According to univariate analysis, MTV, TLG and tumor size were significant risk factors for PFS and OS (p<0.05). However, SUVmax was not a significant factor for PFS and OS (p>0.05). Conclusions: The present study suggested that total lesion glycolysis and metabolic tumor volume were important predictors of survival in lung cancer patients, in contrast to SUVmax. In addition, having a segmental lung atelectasis seems not to be a significant factor on survival.
Correlations between mitochondrial respiration, glycolysis activity and overall growth activity of rice (Oryza sativa: cv. Dasan) seedlings during low temperature exposure were studied in order to provide insights into the underlying mechanism for the primary phase of chilling injury in plants. Among cellular membranes involved in energy metabolism, only the mitochondrial inner membrane showed not only physical phase transition at ca. $13^{\circ}C$, as monitored by ESR spin label, but also functional phase transition at the same temperature, as assessed by cytochrome c oxidase activity. The main regulatory enzyme of glycolysis, phosphofructokinase, in situ did not suffer phase transition of its activity at least in the $4{\sim}27^{\circ}C$ range. Low temperature caused a significant accumulation of glucose 6-phosphate (G6P) and fructose 6-phosphate (F6P), which disappeared almost completely on rewarming of the seedlings. Temperature profiles of the steady state levels of G6P and F6P revealed the inflection point appearing at around phase transition temperature of the mitochondrial membrane. The results conform to our previous proposition on the mechanism for the early stage events of chilling injury that the accumulation of glycolytic metabolites in cells due to metabolic imbalance at low temperature gives rise to an excess supply of electrons during rewarming period, which, in turn, results in overproduction of active oxygen in mitochondria.
Hexachlorophene was reported previously to have a powerful parasiticidal effects on Clonorchis sinensis in vitro and in vivo, but the mechanism of its effect was not known. In the present report it was observed that there was an influence of hexachlorophene on the oxygen consumption, the glycolysis, the glycogenesis and the protein synthesis of C. sinensis. A hundred mg. of C. sinensis collected from the biliary tracts of the infested rabbits was incubated in 2 ml of K.R.P. medium with vavious concentration of hexachlorophene, $glucose-1-C^{14}$ and $glycine-1-C^{14}$ in a 25 ml incubation flask with central well. The oxygen consumption was observed by Warburg manometer, the glycogenolysis by measurement of radioactivities of extracted glycogen and protein from C. sinensis incubated with $C^{14}-glucose$ or$C^{14}-glycine$. 1) The oxygen consumption by C. sinensis was markedly inhibited during all stages of incubation in concentration of $10^{-4}$ and $10^{-5}g/ml$ of hexachlorophene, but in $10^{-6}$, slightly increased initially and gradually decreased after 3 hours of incubation. 2) Hexachlorophene inhibited the glycolysis by C. sincnsis markedly in the concentration of $10^{-4}$, $10^{-5}$, $10^{-6}$ and $10^{-7}g/ml$. 3) The protein synthesis by C. sinensis from glycine was inhibited in the concentration of $10^{-5}$, $10^{-6}$ and $10^{-7}g/ml$ of hexachlorophene. 4. The glycogen synthesis by C. sinensis in each concentration of $10^{-4}$, $10^{-5}$ and $10^{-6}g/ml$ of hexachlorophene was inhibited markedly. The speed of inhibition was more rapid in high concentration than in low, and in low concentration even the glycogen itself which had synthesized in their stage in their body was consumed in later stage. 5) The effects of oxygen consumption, glycolysis and glycogen synthesis were not influenced in the concentration of $10^{-5}g/ml$ of chloroquine phosphate, whereas hexachlorophene and dithiazanine inhibited markedly in same concentration, and the former was more potent than the latter.
Phosphosugars are found in all living organisms and are commercially valuable compounds with possible applications in the development of a wide range of specialty chemicals and medicines. In carbohydrate metabolism, fructose 6-phosphate (F6P) is an essential intermediate formed by phosphorylation of 6' position of fructose in glycolysis, gluconeogenesis, pentose phosphate pathway and Calvin cycle. In glycolysis, F6P lies within the glycolysis metabolic pathway and is produced by isomerisation of glucose 6-phosphate. For large-scale production, F6P could be produced from starch using many enzymes such as pullulanase, starch phosphorylase, isomerase and mutase. In enzymatic reactions carried out at high temperatures, the solubility of starch is increased and microbial contamination is minimized. Thus, thermophile-derived enzymes are preferred over mesophile-derived enzymes for industrial applications using starch. Recently, we reported the production of glucose 1-phosphate (G1P) from starch by Thermus caldophilus GK24 enzymes. Here we report the production of F6P from starch through three steps; from starch to glucose 1-phosphate (glucan phosphorylase, GP), then glucose 6-phosphate (phosphoglucomutase, GM) and then F6P (phosphoglucoisomerase, GI). Using 200 L of 1.2% soluble starch solution in potassium phosphate buffer, 1,253 g of G1P were produced. Then, 30% yields of F6P were attained at the optimum reaction conditions of GM : G1 (1 : 2.3), 63.5$^{\circ}C$, and pH 6.85. The optimum conditions were found by response surface methodology and the theoretical values were confirmed by the experiments. The optimum starch concentrations were 20 g/L under the given conditions.
The current study was designed to estimate the pork quality traits using metabolites from exsanguination blood and postmortem muscle simultaneously under the Korean standard pre- and post-slaughter conditions. A total of 111 Yorkshire (pure breed and castrated male) pigs were evaluated under the Korean standard conditions. Measurements were taken of the levels of blood glucose and lactate at exsanguination, and muscle glycogen and lactate content at 45 min and 24 h postmortem. Certain pork quality traits were also evaluated. Correlation analysis and multiple regression analysis including stepwise regression were performed. Exsanguination blood glucose and lactate levels were positively correlated with each other, negatively related to postmortem muscle glycogen content and positively associated with postmortem muscle lactate content. A rapid and extended postmortem glycolysis was associated with high levels of blood glucose and lactate, with high muscle lactate content, and with low muscle glycogen content during postmortem. In addition, these were also correlated with paler meat color and reduced water holding capacity. The results of multiple regression analyses also showed that metabolites in exsanguination blood and postmortem muscle explained variations in pork quality traits. Especially, levels of blood glucose and lactate and content of muscle glycogen at early postmortem were significantly associated with an elevated early glycolytic rate. Furthermore, muscle lactate content at 24 h postmortem alone accounted for a considerable portion of the variation in pork quality traits. Based on these results, the current study confirmed that the main factor influencing pork quality traits is the ultimate lactate content in muscle via postmortem glycolysis, and that levels of blood glucose and lactate at exsanguination and contents of muscle glycogen and lactate at postmortem can explain a large portion of the variation in pork quality even under the standard slaughter conditions.
Kim, Hans H.;Joo, Hyun;Kim, Tae-Ho;Kim, Eui-Yong;Park, Seok-Ju;Park, Ji-Kyoung;Kim, Han-Jip
Interdisciplinary Bio Central
/
v.1
no.2
/
pp.7.1-7.7
/
2009
"To be, or not to be?" This question is not only Hamlet's agony but also the dilemma of mitochondria in a cancer cell. Cancer cells have a high glycolysis rate even in the presence of oxygen. This feature of cancer cells is known as the Warburg effect, named for the first scientist to observe it, Otto Warburg, who assumed that because of mitochondrial malfunction, cancer cells had to depend on anaerobic glycolysis to generate ATP. It was demonstrated, however, that cancer cells with intact mitochondria also showed evidence of the Warburg effect. Thus, an alternative explanation was proposed: the Warburg effect helps cancer cells harness additional ATP to meet the high energy demand required for their extraordinary growth while providing a basic building block of metabolites for their proliferation. A third view suggests that the Warburg effect is a defense mechanism, protecting cancer cells from the higher than usual oxidative environment in which they survive. Interestingly, the latter view does not conflict with the high-energy production view, as increased glucose metabolism enables cancer cells to produce larger amounts of both antioxidants to fight oxidative stress and ATP and metabolites for growth. The combination of these two different hypotheses may explain the Warburg effect, but critical questions at the mechanistic level remain to be explored. Cancer shows complex and multi-faceted behaviors. Previously, there has been no overall plan or systematic approach to integrate and interpret the complex signaling in cancer cells. A new paradigm of collaboration and a well-designed systemic approach will supply answers to fill the gaps in current cancer knowledge and will accelerate the discovery of the connections behind the Warburg mystery. An integrated understanding of cancer complexity and tumorigenesis is necessary to expand the frontiers of cancer cell biology.
본 웹사이트에 게시된 이메일 주소가 전자우편 수집 프로그램이나
그 밖의 기술적 장치를 이용하여 무단으로 수집되는 것을 거부하며,
이를 위반시 정보통신망법에 의해 형사 처벌됨을 유념하시기 바랍니다.
[게시일 2004년 10월 1일]
이용약관
제 1 장 총칙
제 1 조 (목적)
이 이용약관은 KoreaScience 홈페이지(이하 “당 사이트”)에서 제공하는 인터넷 서비스(이하 '서비스')의 가입조건 및 이용에 관한 제반 사항과 기타 필요한 사항을 구체적으로 규정함을 목적으로 합니다.
제 2 조 (용어의 정의)
① "이용자"라 함은 당 사이트에 접속하여 이 약관에 따라 당 사이트가 제공하는 서비스를 받는 회원 및 비회원을
말합니다.
② "회원"이라 함은 서비스를 이용하기 위하여 당 사이트에 개인정보를 제공하여 아이디(ID)와 비밀번호를 부여
받은 자를 말합니다.
③ "회원 아이디(ID)"라 함은 회원의 식별 및 서비스 이용을 위하여 자신이 선정한 문자 및 숫자의 조합을
말합니다.
④ "비밀번호(패스워드)"라 함은 회원이 자신의 비밀보호를 위하여 선정한 문자 및 숫자의 조합을 말합니다.
제 3 조 (이용약관의 효력 및 변경)
① 이 약관은 당 사이트에 게시하거나 기타의 방법으로 회원에게 공지함으로써 효력이 발생합니다.
② 당 사이트는 이 약관을 개정할 경우에 적용일자 및 개정사유를 명시하여 현행 약관과 함께 당 사이트의
초기화면에 그 적용일자 7일 이전부터 적용일자 전일까지 공지합니다. 다만, 회원에게 불리하게 약관내용을
변경하는 경우에는 최소한 30일 이상의 사전 유예기간을 두고 공지합니다. 이 경우 당 사이트는 개정 전
내용과 개정 후 내용을 명확하게 비교하여 이용자가 알기 쉽도록 표시합니다.
제 4 조(약관 외 준칙)
① 이 약관은 당 사이트가 제공하는 서비스에 관한 이용안내와 함께 적용됩니다.
② 이 약관에 명시되지 아니한 사항은 관계법령의 규정이 적용됩니다.
제 2 장 이용계약의 체결
제 5 조 (이용계약의 성립 등)
① 이용계약은 이용고객이 당 사이트가 정한 약관에 「동의합니다」를 선택하고, 당 사이트가 정한
온라인신청양식을 작성하여 서비스 이용을 신청한 후, 당 사이트가 이를 승낙함으로써 성립합니다.
② 제1항의 승낙은 당 사이트가 제공하는 과학기술정보검색, 맞춤정보, 서지정보 등 다른 서비스의 이용승낙을
포함합니다.
제 6 조 (회원가입)
서비스를 이용하고자 하는 고객은 당 사이트에서 정한 회원가입양식에 개인정보를 기재하여 가입을 하여야 합니다.
제 7 조 (개인정보의 보호 및 사용)
당 사이트는 관계법령이 정하는 바에 따라 회원 등록정보를 포함한 회원의 개인정보를 보호하기 위해 노력합니다. 회원 개인정보의 보호 및 사용에 대해서는 관련법령 및 당 사이트의 개인정보 보호정책이 적용됩니다.
제 8 조 (이용 신청의 승낙과 제한)
① 당 사이트는 제6조의 규정에 의한 이용신청고객에 대하여 서비스 이용을 승낙합니다.
② 당 사이트는 아래사항에 해당하는 경우에 대해서 승낙하지 아니 합니다.
- 이용계약 신청서의 내용을 허위로 기재한 경우
- 기타 규정한 제반사항을 위반하며 신청하는 경우
제 9 조 (회원 ID 부여 및 변경 등)
① 당 사이트는 이용고객에 대하여 약관에 정하는 바에 따라 자신이 선정한 회원 ID를 부여합니다.
② 회원 ID는 원칙적으로 변경이 불가하며 부득이한 사유로 인하여 변경 하고자 하는 경우에는 해당 ID를
해지하고 재가입해야 합니다.
③ 기타 회원 개인정보 관리 및 변경 등에 관한 사항은 서비스별 안내에 정하는 바에 의합니다.
제 3 장 계약 당사자의 의무
제 10 조 (KISTI의 의무)
① 당 사이트는 이용고객이 희망한 서비스 제공 개시일에 특별한 사정이 없는 한 서비스를 이용할 수 있도록
하여야 합니다.
② 당 사이트는 개인정보 보호를 위해 보안시스템을 구축하며 개인정보 보호정책을 공시하고 준수합니다.
③ 당 사이트는 회원으로부터 제기되는 의견이나 불만이 정당하다고 객관적으로 인정될 경우에는 적절한 절차를
거쳐 즉시 처리하여야 합니다. 다만, 즉시 처리가 곤란한 경우는 회원에게 그 사유와 처리일정을 통보하여야
합니다.
제 11 조 (회원의 의무)
① 이용자는 회원가입 신청 또는 회원정보 변경 시 실명으로 모든 사항을 사실에 근거하여 작성하여야 하며,
허위 또는 타인의 정보를 등록할 경우 일체의 권리를 주장할 수 없습니다.
② 당 사이트가 관계법령 및 개인정보 보호정책에 의거하여 그 책임을 지는 경우를 제외하고 회원에게 부여된
ID의 비밀번호 관리소홀, 부정사용에 의하여 발생하는 모든 결과에 대한 책임은 회원에게 있습니다.
③ 회원은 당 사이트 및 제 3자의 지적 재산권을 침해해서는 안 됩니다.
제 4 장 서비스의 이용
제 12 조 (서비스 이용 시간)
① 서비스 이용은 당 사이트의 업무상 또는 기술상 특별한 지장이 없는 한 연중무휴, 1일 24시간 운영을
원칙으로 합니다. 단, 당 사이트는 시스템 정기점검, 증설 및 교체를 위해 당 사이트가 정한 날이나 시간에
서비스를 일시 중단할 수 있으며, 예정되어 있는 작업으로 인한 서비스 일시중단은 당 사이트 홈페이지를
통해 사전에 공지합니다.
② 당 사이트는 서비스를 특정범위로 분할하여 각 범위별로 이용가능시간을 별도로 지정할 수 있습니다. 다만
이 경우 그 내용을 공지합니다.
제 13 조 (홈페이지 저작권)
① NDSL에서 제공하는 모든 저작물의 저작권은 원저작자에게 있으며, KISTI는 복제/배포/전송권을 확보하고
있습니다.
② NDSL에서 제공하는 콘텐츠를 상업적 및 기타 영리목적으로 복제/배포/전송할 경우 사전에 KISTI의 허락을
받아야 합니다.
③ NDSL에서 제공하는 콘텐츠를 보도, 비평, 교육, 연구 등을 위하여 정당한 범위 안에서 공정한 관행에
합치되게 인용할 수 있습니다.
④ NDSL에서 제공하는 콘텐츠를 무단 복제, 전송, 배포 기타 저작권법에 위반되는 방법으로 이용할 경우
저작권법 제136조에 따라 5년 이하의 징역 또는 5천만 원 이하의 벌금에 처해질 수 있습니다.
제 14 조 (유료서비스)
① 당 사이트 및 협력기관이 정한 유료서비스(원문복사 등)는 별도로 정해진 바에 따르며, 변경사항은 시행 전에
당 사이트 홈페이지를 통하여 회원에게 공지합니다.
② 유료서비스를 이용하려는 회원은 정해진 요금체계에 따라 요금을 납부해야 합니다.
제 5 장 계약 해지 및 이용 제한
제 15 조 (계약 해지)
회원이 이용계약을 해지하고자 하는 때에는 [가입해지] 메뉴를 이용해 직접 해지해야 합니다.
제 16 조 (서비스 이용제한)
① 당 사이트는 회원이 서비스 이용내용에 있어서 본 약관 제 11조 내용을 위반하거나, 다음 각 호에 해당하는
경우 서비스 이용을 제한할 수 있습니다.
- 2년 이상 서비스를 이용한 적이 없는 경우
- 기타 정상적인 서비스 운영에 방해가 될 경우
② 상기 이용제한 규정에 따라 서비스를 이용하는 회원에게 서비스 이용에 대하여 별도 공지 없이 서비스 이용의
일시정지, 이용계약 해지 할 수 있습니다.
제 17 조 (전자우편주소 수집 금지)
회원은 전자우편주소 추출기 등을 이용하여 전자우편주소를 수집 또는 제3자에게 제공할 수 없습니다.
제 6 장 손해배상 및 기타사항
제 18 조 (손해배상)
당 사이트는 무료로 제공되는 서비스와 관련하여 회원에게 어떠한 손해가 발생하더라도 당 사이트가 고의 또는 과실로 인한 손해발생을 제외하고는 이에 대하여 책임을 부담하지 아니합니다.
제 19 조 (관할 법원)
서비스 이용으로 발생한 분쟁에 대해 소송이 제기되는 경우 민사 소송법상의 관할 법원에 제기합니다.
[부 칙]
1. (시행일) 이 약관은 2016년 9월 5일부터 적용되며, 종전 약관은 본 약관으로 대체되며, 개정된 약관의 적용일 이전 가입자도 개정된 약관의 적용을 받습니다.