• BMB Reports
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• 제51권11호
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• pp.557-562
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• 2018

Reactive oxygen species (ROS) are major sources of cellular oxidative stress. Specifically, cancer cells harbor genetic alterations that promote a continuous and elevated production of ROS. While such oxidative stress conditions could be harmful to normal cells, they facilitate cancer cell growth in multiple ways by causing DNA damage and genomic instability, and ultimately by reprogramming cancer cell metabolism. This review provides up to date findings regarding the roles of ROS generation induced by diverse biological molecules and chemicals in representative women's cancer. Specifically, we describe the cellular signaling pathways that regulate direct or indirect interactions between ROS homeostasis and metabolism within female genital cancer cells.

• BMB Reports
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• 제47권3호
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• pp.141-148
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• 2014

Bone is an active tissue, in which bone formation by osteoblast is followed by bone resorption by osteoclasts, in a repeating cycle. Proteomics approaches may allow the detection of changes in cell signal transduction, and the regulatory mechanism of cell differentiation. LC-MS/MS-based quantitative methods can be used with labeling strategies, such as SILAC, iTRAQ, TMT and enzymatic labeling. When used in combination with specific protein enrichment strategies, quantitative proteomics methods can identify various signaling molecules and modulators, and their interacting proteins in bone metabolism, to elucidate biological functions for the newly identified proteins in the cellular context. In this article, we will briefly review recent major advances in the application of proteomics for bone biology, especially from the aspect of cellular signaling.

• Archives of Pharmacal Research
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• 제11권2호
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• pp.114-121
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• 1988

To gain insight into possible cellular protective mechanisms against the insult of formaldehyde, we have investigated this molecule's reactivity with both naturally occurring thiol compounds including glutathione and L-ascorbic acid. By UV measurements, for maldehyde was found to rapidly react with glutathione forming an S-hydroxymethyl covalent adduct. The adduct which was confirmed by NMR is transiently stable. Formaldehydissimilar to its reaction with dimedone. The reaction of formaldehyde with glutathione was reduced by 40% in the presence of an excess amount of L-ascorbic acid, due to the trapping of formaldehyde by L-ascorbic acid. The data suggest that L-ascorbic acid may have a possible in vivo role in the metabolism of formaldehyde, thereby protecting cellular glutathione from possible depletion.

• Integrative Medicine Research
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• 제2권4호
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• pp.131-138
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• 2013

The skeletal muscle in our body is a major site for bioenergetics and metabolism during exercise. Carbohydrates and fats are the primary nutrients that provide the necessary energy required to maintain cellular activities during exercise. The metabolic responses to exercise in glucose and lipid regulation depend on the intensity and duration of exercise. Because of the increasing prevalence of obesity, recent studies have focused on the cellular and molecular mechanisms of obesity-induced insulin resistance in skeletal muscle. Accumulation of intramyocellular lipid may lead to insulin resistance in skeletal muscle. In addition, lipid intermediates (e.g., fatty acyl-coenzyme A, diacylglycerol, and ceramide) impair insulin signaling in skeletal muscle. Recently, emerging evidence linking obesity-induced insulin resistance to excessive lipid oxidation, mitochondrial overload, and mitochondrial oxidative stress have been provided with mitochondrial function. This review will provide a brief comprehensive summary on exercise and skeletal muscle metabolism, and discuss the potential mechanisms of obesity-induced insulin resistance in skeletal muscle.

• Journal of Medicine and Life Science
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• 제15권2호
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• pp.37-41
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• 2018

Mitochondrial injury in renal tubule has been recognized as a major contributor in acute kidney injury (AKI) pathogenesis. Ischemic insult, nephrotoxin, endotoxin and contrast medium destroy mitochondrial structure and function as well as their biogenesis and dynamics, especially in renal proximal tubule, to elicit ATP depletion. Mitochondrial fatty acid ${\beta}$-oxidation (FAO) is the preferred source of ATP in the kidney, and its impairment is a critical factor in AKI pathogenesis. This review explores current knowledge of mitochondrial dysfunction and energy depletion in AKI and prospective views on developing therapeutic strategies targeting mitochondrial dysfunction in AKI.

• Journal of Nutrition and Health
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• 제30권1호
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• pp.3-11
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• 1997

This study was conducted to investigate the effects of protein levels and casein/whey ratios on organ growth and protein metabolism in early weaned rats. Premature rats weaned by the 17th day were fed six semipurified synthetic, isocaloric and gel diets that contained three levels (low, medium and high) and two different combinations(casein/whey ; 80 : 20 or 20 : 80) of milk protein for 8 days. On the 25th day postpartum, frest weigth and DNA, RNA and milk protein contents in brain, liver, kidney and muscle were determined to ascertain organ and cellular growth. Futher, with a view to ascertain protein metabolism and renal functions, serum total protein, $\alpha$-amino N, urea N, and creatinine and creatinine and urinary urea N, creatinine and hydroxproline were determined. Total DNA contents of brain, liver and kidney, which may represent as an index of cell numbers in those organs were significantly decreased in the rats fed diets containing low level protein regardless of casein/whey ratio. However, as fat as the rats fed high protein diets were concerned, their fresh weight, protein contents and GFR of kidney were significantly increased. Furthermore, nitrogen components, $\alpha$-amino N, urea N and creatinie in serum and urine were also increassed. Another observation was that high casein/whey ratio significantly facilitated accumulation of porteins in muscle and kidney and urinary hydorxyproline excretion, not affecting the DNA content of those organs. This study showed that low(8%) or high(32%) contents of protein had less desirable effects either on protein metabolism or on organ cellular growth in prematurely weaned rats, whereas there were no effects on general growth and bone strength.

• 고려인삼학회:학술대회논문집
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• 고려인삼학회 1984년도 학술대회지
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• pp.141-144
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• 1984

인삼이 강장제인 약용식물로 인식됨에 따라 세포에 대한 인삼 추출물의 효과를 연구하기 위해 미생물을 실험재료로 연구한 결과, 인삼이 두 단계로 세포 호흡에 영향을 미치는 것으로 관찰되었으며 (Tso and Fung, Microbios, Lett. 13 : $7{\~}12$., Tso, Acta Microbiologies sinica 21 : $53{\~}56$)이것은 세포 에너지 대사 변화에 중요한 역할을 할 수 있다는 것을 시사해 주었다. 이와 같은 결과로 인삼이 세포의 mitochondria 에 의한 산소 소모에 미치는 효과를 검토한 결과, 일정한 pH 조건하에서 인삼은 호흡을 촉진시켰으며, 일정농도 이상 투여하였을 경우 다소의 억제효과를 보였다. 위의 결과들은 세포의 mitochonbria 호흡에 미치는 인삼의 효과를 재확인하는 것으로 강장제로서의 인삼의 가치를 뒷받침해 주고 있다.

• Kidney Research and Clinical Practice
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• 제35권2호
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• pp.69-77
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• 2016

Diabetic nephropathy (DN) is the leading cause of end-stage renal disease, and its pathogenesis is complex and has not yet been fully elucidated. Abnormal glucose and lipid metabolism is key to understanding the pathogenesis of DN, which can develop in both type 1 and type 2 diabetes. A hallmark of this disease is the accumulation of glucose and lipids in renal cells, resulting in oxidative and endoplasmic reticulum stress, intracellular hypoxia, and inflammation, eventually leading to glomerulosclerosis and interstitial fibrosis. There is a growing body of evidence demonstrating that dysregulation of 50 adenosine monophosphate-activated protein kinase (AMPK), an enzyme that plays a principal role in cell growth and cellular energy homeostasis, in relevant tissues is a key component of the development of metabolic syndrome and type 2 diabetes mellitus; thus, targeting this enzyme may ameliorate some pathologic features of this disease. AMPK regulates the coordination of anabolic processes, with its activation proven to improve glucose and lipid homeostasis in insulin-resistant animal models, as well as demonstrating mitochondrial biogenesis and antitumor activity. In this review, we discuss new findings regarding the role of AMPK in the pathogenesis of DN and offer suggestions for feasible clinical use and future studies of the role of AMPK activators in this disorder.

• Molecules and Cells
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• 제46권4호
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• pp.200-205
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• 2023

DNA-dependent protein kinase catalytic subunit (DNA-PKcs), a member of the phosphatidylinositol 3-kinase-related kinase family is a well-known player in repairing DNA double-strand break through non-homologous end joining pathway. This mechanism has allowed us to understand its critical role in T and B cell development through V(D)J recombination and class switch recombination, respectively. We have also learned that the defects in these mechanisms lead to the severely combined immunodeficiency (SCID). Here we highlight some of the latest evidence where DNA-PKcs has been shown to localize not only in the nucleus but also in the cytoplasm, phosphorylating various proteins involved in cellular metabolism and cytokine production. While it is an exciting time to unveil novel functions of DNA-PKcs, one should carefully choose experimental models to study DNA-PKcs as the experimental evidence has been shown to differ between cells of defective DNA-PKcs and those of DNA-PKcs knockout. Moreover, while there are several DNA-PK inhibitors currently being evaluated in the clinical trials in an attempt to increase the efficacy of radiotherapy or chemotherapy, multiple functions and subcellular localization of DNA-PKcs in various types of cells may further complicate the effects at the cellular and organismal level.

• Molecules and Cells
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• 제43권3호
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• pp.222-227
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• 2020

Inositol polyphosphate multikinase (IPMK) is required for the biosynthesis of inositol phosphates (IPs) through the phosphorylation of multiple IP metabolites such as IP3 and IP4. The biological significance of IPMK's catalytic actions to regulate cellular signaling events such as growth and metabolism has been studied extensively. However, pharmacological reagents that inhibit IPMK have not yet been identified. We employed a structure-based virtual screening of publicly available U.S. Food and Drug Administration-approved drugs and chemicals that identified the antidepressant, vilazodone, as an IPMK inhibitor. Docking simulations and pharmacophore analyses showed that vilazodone has a higher affinity for the ATP-binding catalytic region of IPMK than ATP and we validated that vilazodone inhibits IPMK's IP kinase activities in vitro. The incubation of vilazodone with NIH3T3-L1 fibroblasts reduced cellular levels of IP5 and other highly phosphorylated IPs without influencing IP4 levels. We further found decreased Akt phosphorylation in vilazodone-treated HCT116 cancer cells. These data clearly indicate selective cellular actions of vilazodone against IPMK-dependent catalytic steps in IP metabolism and Akt activation. Collectively, our data demonstrate vilazodone as a method to inhibit cellular IPMK, providing a valuable pharmacological agent to study and target the biological and pathological processes governed by IPMK.