Effects of cisplatin on mitochondrial function and autophagy-related proteins in skeletal muscle of rats

( Dae Yun Seo ),( Jun Hyun Bae ),( Didi Zhang ),( Wook Song ),( Hyo-bum Kwak ),( Jun-won Heo ),( Su-jeen Jung ),( Hyeong Rok Yun ),( Tae Nyun Kim ),( Sang Ho Lee ),( Amy Hyein Kim ),( Dae Hoon Jeong ) 생화학분자생물학회 2021 BMB Reports Vol.54 No.11

Cisplatin is widely known as an anti-cancer drug. However, the effects of cisplatin on mitochondrial function and autophagy-related proteins levels in the skeletal muscle are unclear. The purpose of this study was to investigate the effect of different doses of cisplatin on mitochondrial function and autophagy-related protein levels in the skeletal muscle of rats. Eight-week-old male Wistar rats (n = 24) were assigned to one of three groups; the first group was administered a saline placebo (CON, n = 10), and the second and third groups were given 0.1 mg/kg body weight (BW) (n = 6), and 0.5 mg/kg BW (n = 8) of cisplatin, respectively. The group that had been administered 0.5 mg cisplatin exhibited a reduced BW, skeletal muscle tissue weight, and mitochondrial function and upregulated levels of autophagy-related proteins, including LC3II, Beclin 1, and BNIP3. Moreover, this group had a high LC3 II/I ratio in the skeletal muscle; i.e., the administration of a high dose of cisplatin decreased the muscle mass and mitochondrial function and increased the levels of autophagy-related proteins. These results, thus, suggest that reducing mitochondrial dysfunction and autophagy pathways may be important for preventing skeletal muscle atrophy following cisplatin administration. [BMB Reports 2021; 54(11): 575-580]

Adsorptive Desulfurization of Diesel for Fuel Cell Applications: A Screening Test

Hoang Phuoc Ho,Woo Hyeong Kim,So-Yun Lee,Hong-Rok Son,Nak Hyeon Kim,Jae-Kon Kim,Jo-Yong Park,Hee Chul Woo 한국청정기술학회 2014 청정기술 Vol.20 No.1

경유는 연료전지 시스템의 연료원으로써 주목받고 있는 탄화수소 액체연료 중 하나로, 연료개질 촉매와 연료전지의 전극재료를 피독시키는 황화합물을 포함하고 있어 탈황공정이 필요한 것으로 여겨지고 있다. 다양하고도 대안적인 탈황기술이 연구되고 있으나, 초저유황 경유의 탈황 연구는 여전히 부진한 실정이다. 본 연구는 용융탄산염 연료전지 시스템에 응용될 수 있는 원료인 상용초저유황 경유의 탈황에 관한 것이다. 여기서 초저유황의 흡착탈황을 위한 흡착제로 활성탄, 제올라이트, 금속산화물 계 상용흡착제 후보군이 선정되었고 유망한 탈황제를 찾기 위한 스크리닝 평가를 실시하였다. 그 결과 초저유황 경유의 황농도를 0.1 ppmw 수준까지 떨어뜨리기 위한 흡착제 종류로 금속산화물계가 매우 유용하며, 활성탄과 제올라이트 흡착제는 같은 실험조건에서 해당 수준의 황 농도에 이르지 못하는 것으로 나타났다. During the past decades much attention has been paid to the desulfurization of diesel oil which is important as a source for the fuel cells to prevent the sulfur poisoning of both diesel steam reforming catalyst and electrode of fuel cell. Although alternative desulfurization techniques have been investigated, desulfurization for ultra-low sulfur diesel (ULSD) is still challenged. Therefore, this research focuses on the desulfurization of commercial ULSD for the application to molten carbonate fuel cell (MCFC). Herein, the performances of several kinds of commercial adsorbents based on activated carbons, zeolites, and metal oxides for desulfurization of ULSD were screened. The results showed that metal oxides based materials can feasibly reduce sulfur concentration in ULSD to a level of 0.1 ppmw while activated carbons and zeolites did not reach this level at current conditions.

새로운 항생제 및 항진균제 개발 동향

김경록,윤태미,권형진,서주원,Kim, Gyeong-Rok,Yun, Tae-Mi,Gwon, Hyeong-Jin,Seo, Ju-Won 한국미생물학회 2006 微生物과 産業 Vol.32 No.2

Adsorptive Desulfurization of Diesel for Fuel Cell Applications: A Screening Test

Ho, Hoang Phuoc,Kim, Woo Hyeong,Lee, So-Yun,Son, Hong-Rok,Kim, Nak Hyeon,Kim, Jae-Kon,Park, Jo-Yong,Woo, Hee Chul The Korean Society of Clean Technology 2014 청정기술 Vol.20 No.1

경유는 연료전지 시스템의 연료원으로써 주목받고 있는 탄화수소 액체연료 중 하나로, 연료개질 촉매와 연료전지의 전극재료를 피독시키는 황화합물을 포함하고 있어 탈황공정이 필요한 것으로 여겨지고 있다. 다양하고도 대안적인 탈황기술이 연구되고 있으나, 초저유황 경유의 탈황 연구는 여전히 부진한 실정이다. 본 연구는 용융탄산염 연료전지 시스템에 응용될 수 있는 원료인 상용초저유황 경유의 탈황에 관한 것이다. 여기서 초저유황의 흡착탈황을 위한 흡착제로 활성탄, 제올라이트, 금속산화물 계 상용흡착제 후보군이 선정되었고 유망한 탈황제를 찾기 위한 스크리닝 평가를 실시하였다. 그 결과 초저유황 경유의 황농도를 0.1 ppmw 수준까지 떨어뜨리기 위한 흡착제 종류로 금속산화물계가 매우 유용하며, 활성탄과 제올라이트 흡착제는 같은 실험조건에서 해당 수준의 황 농도에 이르지 못하는 것으로 나타났다. During the past decades much attention has been paid to the desulfurization of diesel oil which is important as a source for the fuel cells to prevent the sulfur poisoning of both diesel steam reforming catalyst and electrode of fuel cell. Although alternative desulfurization techniques have been investigated, desulfurization for ultra-low sulfur diesel (ULSD) is still challenged. Therefore, this research focuses on the desulfurization of commercial ULSD for the application to molten carbonate fuel cell (MCFC). Herein, the performances of several kinds of commercial adsorbents based on activated carbons, zeolites, and metal oxides for desulfurization of ULSD were screened. The results showed that metal oxides based materials can feasibly reduce sulfur concentration in ULSD to a level of 0.1 ppmw while activated carbons and zeolites did not reach this level at current conditions.

Mitochondrial ROS-derived PTEN oxidation activates PI3K pathway for mTOR-induced myogenic autophagy

Kim, Jin-Hwan,Choi, Tae Gyu,Park, Seolhui,Yun, Hyeong Rok,Nguyen, Ngoc Ngo Yen,Jo, Yong Hwa,Jang, Miran,Kim, Jieun,Kim, Joungmok,Kang, Insug,Ha, Joohun,Murphy, Michael P.,Tang, Dean G.,Kim, Sung Soo Nature Publishing Group 2018 Cell death and differentiation Vol.25 No.11

Cyclophilin B induces chemoresistance by degrading wild‐type p53 via interaction with MDM2 in colorectal cancer

Choi, Tae Gyu,Nguyen, Minh Nam,Kim, Jieun,Jo, Yong Hwa,Jang, Miran,Nguyen, Ngoc Ngo Yen,Yun, Hyeong Rok,Choe, Wonchae,Kang, Insug,Ha, Joohun,Tang, Dean G,Kim, Sung Soo John Wiley Sons, Ltd 2018 The Journal of pathology Vol.246 No.1

<P><B>Abstract</B></P><P>Colorectal cancer (CRC) is one of the leading causes of cancer‐related deaths worldwide. Chemoresistance is a major problem for effective therapy in CRC. Here, we investigated the mechanism by which peptidylprolyl isomerase B (PPIB; cyclophilin B, CypB) regulates chemoresistance in CRC. We found that CypB is a novel wild‐type p53 (p53WT)‐inducible gene but a negative regulator of p53WT in response to oxaliplatin treatment. Overexpression of CypB shortens the half‐life of p53WT and inhibits oxaliplatin‐induced apoptosis in CRC cells, whereas knockdown of CypB lengthens the half‐life of p53WT and stimulates p53WT‐dependent apoptosis. CypB interacts directly with MDM2, and enhances MDM2‐dependent p53WT ubiquitination and degradation. Furthermore, we firmly validated, using bioinformatics analyses, that overexpression of CypB is associated with poor prognosis in CRC progression and chemoresistance. Hence, we suggest a novel mechanism of chemoresistance caused by overexpressed CypB, which may help to develop new anti‐cancer drugs. We also propose that CypB may be utilized as a predictive biomarker in CRC patients. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.</P>

Metformin Alleviates Radiation-Induced Skin Fibrosis via the Downregulation of FOXO3

Kim, Jin-Mo,Yoo, Hyun,Kim, Jee-Youn,Oh, Sang Ho,Kang, Jeong Wook,Yoo, Byung Rok,Han, Song Yee,Kim, Cha Soon,Choi, Won Hoon,Lee, Eun-Jung,Byeon, Hyeong Ju,Lee, Won Jai,Lee, Yun-Sil,Cho, Jaeho S. Karger AG 2018 CELLULAR PHYSIOLOGY AND BIOCHEMISTRY Vol.48 No.3

<P><B><I>Background/Aims:</I></B> Radiation-induced skin fibrosis is a common side effect of clinical radiotherapy. Our previous next-generation sequencing (NGS) study demonstrated the reduced expression of the regulatory α subunit of phosphatidylinositol 3-kinase (PIK3r1) in irradiated murine skin. Metformin has been reported to target the PIK3-FOXO3 pathway. In this study, we investigated the effects of metformin on radiation-induced skin fibrosis. <B><I>Methods:</I></B> Metformin was orally administered to irradiated mice. Skin fibrosis was analyzed by staining with H&E and Masson’s trichrome stain. The levels of cytokines and chemokines associated with fibrosis were analyzed by immunohistochemistry and quantitative RT-PCR. The roles of PIK3rl and FOXO3 in radiation-induced skin fibrosis were studied by overexpressing PIK3rl and transfecting FOXO3 siRNA in NIH3T3 cells and mouse-derived dermal fibroblasts (MDF). <B><I>Results:</I></B> The oral administration of metformin significantly reduced radiation-induced skin thickening and collagen accumulation and significantly reduced the radiation-induced expression of FOXO3 in murine skin. Additionally, the overexpression of PIK3r1 reduced the radiation-induced expression of FOXO3, while FOXO3 silencing decreased the radiation-induced expression of TGFβ <I>in vitro</I>. <B><I>Conclusions:</I></B> The results indicated that metformin suppresses radiation-induced skin injuries by modulating the expression of FOXO3 through PIK3r1. Collectively, the data obtained in this study suggested that metformin could be a potent therapeutic agent for alleviating radiation-induced skin fibrosis.</P>

Evogliptin, a DPP-4 inhibitor, prevents diabetic cardiomyopathy by alleviating cardiac lipotoxicity in db/db mice

Pham Trong Kha,Nguyen To Hoai T.,Yi Joo Mi,Kim Gwang Sil,Yun Hyeong Rok,Kim Hyoung Kyu,Won Jong Chul 생화학분자생물학회 2023 Experimental and molecular medicine Vol.55 No.-

Dipeptidyl peptidase-4 (DPP-4) inhibitors are glucose-lowering drugs for type 2 diabetes mellitus (T2DM). We investigated whether evogliptin® (EVO), a DPP-4 inhibitor, could protect against diabetic cardiomyopathy (DCM) and the underlying mechanisms. Eight-week-old diabetic and obese db/db mice were administered EVO (100 mg/kg/day) daily by oral gavage for 12 weeks. db/db control mice and C57BLKS/J as wild-type (WT) mice received equal amounts of the vehicle. In addition to the hypoglycemic effect, we examined the improvement in cardiac contraction/relaxation ability, cardiac fibrosis, and myocardial hypertrophy by EVO treatment. To identify the mechanisms underlying the improvement in diabetic cardiomyopathy by EVO treatment, its effect on lipotoxicity and the mitochondrial damage caused by lipid droplet accumulation in the myocardium were analyzed. EVO lowered the blood glucose and HbA1c levels and improved insulin sensitivity but did not affect the body weight or blood lipid profile. Cardiac systolic/diastolic function, hypertrophy, and fibrosis were improved in the EVO-treated group. EVO prevented cardiac lipotoxicity by reducing the accumulation of lipid droplets in the myocardium through suppression of CD36, ACSL1, FABP3, PPARgamma, and DGAT1 and enhancement of the phosphorylation of FOXO1, indicating its inhibition. The EVO-mediated improvement in mitochondrial function and reduction in damage were achieved through activation of PGC1a/NRF1/TFAM, which activates mitochondrial biogenesis. RNA-seq results for the whole heart confirmed that EVO treatment mainly affected the differentially expressed genes (DEGs) related to lipid metabolism. Collectively, these findings demonstrate that EVO improves cardiac function by reducing lipotoxicity and mitochondrial injury and provides a potential therapeutic option for DCM.