• Journal of Applied Biological Chemistry
• /
• v.65 no.4
• /
• pp.387-396
• /
• 2022

Skeletal muscle accounts for about 40-50% of body weight and is an important tissue that performs various functions, such as maintaining posture, supporting soft tissues, maintaining body temperature, and respiration. Cancer, which occurs widely around the world, causes cancer cachexia accompanied by muscular atrophy, which reduces the effectiveness of anticancer drugs and greatly reduces the quality of life and survival rate of cancer patients. Therefore, research to improve cancer cachexia is ongoing. However, there are few studies on the link between cancer and muscle atrophy. Cancer cells exhibit distinct microenvironment and metabolism from tumor cells, including tumor-associated macrophages (TAM), tumor-associated neutrophils (TAN), and insulin resistance due to the Warburg effect. Therefore, we summarize the microenvironment and metabolic characteristics of cancer cells, and the molecular mechanisms of muscle atrophy that can be affected by cytokine and insulin resistance. In addition, this suggests the possibility of improving cancer cachexia of substances affecting TAM, TAN, and Warburg effect. We also summarize the mechanisms identified so far through single agents and the signaling pathways mediated by them that may ameliorate cancer cachexia.

• Journal of Life Science
• /
• v.28 no.12
• /
• pp.1469-1476
• /
• 2018

Occurrence of the Warburg effect in solid tumors causes resistance to cancer chemotherapy, and targeting energy metabolisms such as aerobic glycolysis is a potential strategy for alternative treatment. Dichloroacetate (DCA), an inhibitor of pyruvate dehydrogenase kinase (PDK), shifts glucose metabolism from aerobic glycolysis to oxidative phosphorylation (OxPhos) in many cancers. In this study, we investigated the anticancer effect of DCA on a human anaplastic thyroid cancer (ATC) cell line, 8505C. We found that DCA selectively inhibits cell proliferation of the 8505C line but not of a normal thyroid line. In 8505C, the cell cycle was arrested at the G1/S phase with DCA treatment as a result of decreased antiapoptotic proteins such as $HIF1{\alpha}$, PDK1, and Bcl-2 and increased proapoptotic proteins such as Bax and p21. DCA treatment enhanced the production of reactive oxygen species which consequently induced cell cycle arrest and apoptosis. Interestingly, DCA treatment not only reduced lactate production but also increased the expression of sodium-iodine symporter, indicating that it restores the OxPhos of glucose metabolism and the iodine metabolism of the ATC. Taken together, our findings suggest that PDK inhibitors such as DCA could be useful anticancer drugs for the treatment of ATC and may also be helpful in combination with chemotherapy and radiotherapy.

• Korean Journal of Microbiology
• /
• v.21 no.3
• /
• pp.149-155
• /
• 1983

Pseudomonas fluorescens, which had been known to be unable to degrade furfural, could utilize 0.03% of furfural as a sole carbon source in a culture with forced aeration. Lag period of this strain was lengthened by low concentration of furfural and growth yield reduced. High concentration of furfural over 0.1% showed killing effect on this strain. Cells of higher metabolic activity and of earlier growth stage were affected more seriously. The fact that even 0.05% of furfural showed no inhibition on respiration of this strain was confirmed with data on respiration rate in Warburg manometr. From these results, it was suggested that furfural show no inhibitory effect on external respination activities of P.fluorescens.

• The Magazine of the Society of Air-Conditioning and Refrigerating Engineers of Korea
• /
• v.29 no.4
• /
• pp.48-54
• /
• 2000

자성재료에 자기장을 걸어주변 가열되고 자기장을 제거하면 냉각되는 성질이 있는데, 이를 자기열량효과(magnetocaloric effect)라고 하며, 이것을 이용해서 저온을 생성시키는 방법을 자기냉동(magnetic refrigeration)이라고 한다. 큐리 온도(Curie temperature) 부근의 강자성체에 자 기장이 가해지면 전자례도내에서 쌍을 이루지 않은 전자들의 자기모벤트들이 자기장에 평행 하게 배열되는데, 이로 인해 열역학적 무질서의 척도인 엔트로피는 낮아지고 이러한 손실을 보상하기 위해 재료의 온도가 올라가게 된다.반대로 자기장이 제거되면 자기모벤트가 본래의 무질서한 상태로 돌아오며, 엔트로피가 증가하 고 재료의 온도는 떨어지게 되는 것이다. 역사적으로 보면 1881년에 Warburg가 큐리온도 부근의 철에서 자기열량효과를 처음 발견하였으며. 1926년과 1927년에 Debye와 Giauque가 각각 단열소자볍 (adiabatic demagnetization)을 제안함으로써 실용화되기 시작하여 주로 극저온을 얻는 방법으로 이용되어 왔다. 1950년도 이전의 연구는 절대온도 영도(OK)에 도달하고 자 하는 순수과학적인 노력으로서 개방사이클(open cycle)을 이용한 단열냉각 방식을 추구하 였으나, 1950년 이후부터는 공학적인 응용을 목적으로 밀폐사이클(closed cycle)을 형성하는 자기냉동기에 관한 연구가 진행되었다. 1976년에 Brown은 희토류(rare earth) 금속인 가돌리늄(Gd)을 사용하여 유체(물 80%와 에틸 알코올 20%)를 재생시킴으로써 상온에서 작동 하는 자기냉동기를 보고한 바 있다. 그는 7 T의 큰 자장을 이용하였으며, 고온부와 저온부의 온도는 각각 $46^{\circ}C와\;-1^{\circ}C로서\;47^{\circ}C$의 온도간격을 얻었다. 자기냉동에 있어서의 또 하나의 중요한 진전은 1978년과 1982년에 Steyert와 Barclay에 의해서 능동자기재생기(active magnetic r regenerator)의 개념이 소개되고 개발된 것으로, 이는 자성재료가 냉매로서 뿐만 아니라 열전달 유체의 재생기로도 사용되는 방식이다. 이상과 같은 자기냉동기술의 발달에 이어서 1997년에 미국의 Astronautics사(Wisconsin주 Madison시 소재)와 Ames 연구소(Iowa주 Ames 시 소재)의 공동연구팀이 발표한 두 가지의 새로운 진전으로 인해 공기조화 및 냉동분야에 적용할 수 있는 자기냉동기의 실용화 가능성이 한층 높아졌다. 이들의 연구결과는 (1) 자기냉동이 실온에서도 실현 가능한 기술이며 증기압 축식 냉동에 필적할 만하다는 것을 보인 것과 (2) 이미 알려져 있던 자기냉동재료보다 자기 열량효과가 훨씬 큰 새로운 재료를 발견한 것이다. 이로써 자기냉동에 대한 관심과 기대가 한결 커지고 있다. 본 원고에서는 자기냉동의 원리가 되는 자기열량효과와 이를 이용한 자기냉동의 방법 그리고 최근에 이루어진 새로운 진전에 대해 소개하고 공기조화 및 냉동분야에의 적용 가능성을 전망해 보고자 한다.

• Journal of Life Science
• /
• v.31 no.5
• /
• pp.464-474
• /
• 2021

Inflammation induced by metabolic syndromes, cancers, injuries, and sepsis can alter cellular metabolism by reducing mitochondrial function via oxidative stress, thereby resulting in neuropathy and muscle atrophy. In this study, we investigated whether butyrate, a short chain fatty acid produced by gut microbiota, could prevent mitochondrial dysfunction and muscle atrophy induced by lipopolysaccharide (LPS) in the C2C12 cell line. LPS-activated MAPK signaling pathways increased the levels of the mitochondrial fission signal, p-DRP1 (Ser616), and the muscle atrophy marker, atrogin 1. Interestingly, butyrate significantly inhibited the phosphorylation of JNK and p38 and reduced the atrogin 1 level in LPS-treated C2C12 cells while increasing the phosphorylation of DRP1 (Ser637) and levels of mitofusin2, which are both mitochondrial fusion markers. Next, we investigated the effect of MAPK inhibitors, finding that butyrate had the same effect as JNK inhibition in C2C12 cells. Also, butyrate inhibited the LPS-induced expression of pyruvate dehydrogenase kinase 4 (PDK4), resulting in decreased PDHE1α phosphorylation and lactate production, suggesting that butyrate shifted glucose metabolism from aerobic glycolysis to oxidative phosphorylation. Finally, we found that these effects of butyrate on LPS-induced mitochondrial dysfunction were caused by its antioxidant effects. Thus, our findings demonstrate that butyrate prevents LPS-induced muscle atrophy by improving mitochondrial dynamics and metabolic stress via the inhibition of JNK phosphorylation. Consequently, butyrate could be used to improve LPS-induced mitochondrial dysfunction and myopathy in sepsis.

• The Korean Journal of Physiology
• /
• v.4 no.2
• /
• pp.45-51
• /
• 1970

In an attempt to better understand the effect of whole body irradiation on the spontaneous motility and oxygen consumption rate of the isolated mouse duodenum, a whole body X-irradiation of 1,000r. was given to albino mouse, and 1) the total length of contraction of isolated duodenum was recorded on kymograph every five minutes for 60 minutes, 2) glucose and 5-hydroxytryptamine(5-HT) were added to the reaction medium of Kreb's-Ringer-bicarbonate buffer(KRB) and response of the isolated duodenum to the drugs was observed, and 3) the oxygen consumption rate $(QO_2)$ of the isolated duodenum as well as the effect of glucose and 5-HT on $QO_2$ were measured by Warburg's standard manometric method and the comparison was made with the control(i.e. normal) group. The results thus obtained are summarized as follows. 1. The spontaneous motility of the isolated duodenum in the irradiated groups showed a significantly elevated pattern for the first 15 minutes comparing with the control. The motility, however, decreased after 15 minutes and remained so in the irradiated groups to the level of the nonirradiated control, but 24 hours post-irradiation group showed a tendency of an increased motility while one hour post-irradiation group showed no difference comparing with the control. 2. Addition of glucose produced generally elevated motility of the isolated duodenum in both irradiated and non-irradiated groups comparing with the control throughout the experiment, but no difference was observed in contractile amplitude between the irradiated and non·irradiated groups. 3. When 5-HT was added to the irradiated group, the contractile amplitude of isolated duodenum was similar to that of the control, and 5-HT alone caused a slight increase of the motility comparing with the control. 4. The oxygen consumption rate $(QO_2)$ of the isolated duodenum was found to be ,slightly increased in one hour post·irradiated group, but similar in 24 hour post·irradiated group comparing with the control. Glucose produced a significant increase of $QO_2$ in all the groups, but 5-HT produced a tendency of decrease of $QO_2$ in all the groups.