Activation Mechanism of Protein Kinase B by DNA-dependent Protein Kinase Involved in the DNA Repair System

Li, Yuwen,Piao, Longzhen,Yang, Keum-Jin,Shin, Sang-Hee,Shin, Eul-Soon,Park, Kyung-Ah,Byun, Hee-Sun,Won, Min-Ho,Choi, Byung-Lyul,Lee, Hyun-Ji,Kim, Young-Rae,Hong, Jang-Hee,Hur, Gang-Min,Kim, Jeong-Lan Korean Society of ToxicologyKorea Environmental Mu 2008 Toxicological Research Vol.25 No.4

DNA-dependent protein kinase(DNA-PK) is involved in joining DNA double-strand breaks induced by ionizing radiation or V(D)J recombination and is activated by DNA ends and composed of a DNA binding subunit, Ku, and a catalytic subunit, DNA-PKcs. It has been suggested that DNA-PK might be $2^{nd}$ upstream kinase for protein kinase B(PKB). In this report, we showed that Ser473 phosphorylation in the hydrophobic-motif of PKB is blocked in DNA-PK knockout mouse embryonic fibroblast cells(MEFs) following insulin stimulation, while there is no effect on Ser473 phosphorylation in DNA-PK wild type MEF cells. The observation is further confirmed in human glioblastoma cells expressing a mutant form of DNA-PK(M059J) and a wild-type of DNA-PK(M059K), indicating that DNA-PK is indeed important for PKB activation. Furthermore, the treatment of cells with doxorubicin, DNA-damage inducing agent, leads to PKB phosphorylation on Ser473 in control MEF cells while there is no response in DNA-PK knockout MEF cells. Together, these results proposed that DNA-PK has a potential role in insulin signaling as well as DNA-repair signaling pathway.

Discovery of NAD(P)H: Quinone Oxidoreductase 1 (NQO1) as a new player in insulin signaling : Quinone Oxidoreductase 1 (NQO1) as a new player in insulin signaling

Li, Yuwen,Shin, Sanghee,Piao, Longzhen,Yang, Keum-Jin,Shin, Eulsoon,Park, Kyung Ah,Byun, Hee Sun,Won, Minho,Kim, Young-Rae,Lee, Hyunji,Hur, Gangmin,Seok, Jeong Ho,Choi, Hueng-Sik,Shong, Minho,Park, Jo 충남대학교 형질전환복제돼지연구센터 2007 논문집 Vol. No.10

Differentiation potential of Mesenchymal stem cell derived from Bone Marrow

Li, Yuwen,Shin, Eulsoon,Yang, Keum-Jin,Piao, Longzhen,Shin, Sanghee,Kim, Young-Rae,Byun, Hee Sun,Won, Minho,Park, Kyung Ah,Lee, Hyunji,Hur, Gangmin,Seok, Jeong Ho,Kim, Jeong-Lan,Kwon, Gye-Cheol,Park, 충남대학교 형질전환복제돼지연구센터 2007 논문집 Vol. No.10

Discovery of role of NAD(P)H: Quinone Oxidoreductase 1 (NQO1) in insulin signaling : Quinone Oxidoreductase 1 (NQO1) in insulin signaling

Li, Yuwen,Piao, Longzhen,Shin, Sanghee,Yang, Keum-Jin,Shin, Eulsoon,Park, Kyung Ah,Byun, Hee Sun,Won, Minho,Kim, Young-Rae,Lee, Hyunji,Choi, Byung Lyul,Hong, Janghee,Hur, Gang-Min,Seok, Jeong-Ho,Choi, 충남대학교 형질전환복제돼지연구센터 2007 논문집 Vol. No.10

Identification of AMPK activator from twelve pure compounds isolated from <i>Aralia Taibaiensis</i>: implication in antihyperglycemic and hypolipidemic activities

Yuwen Li,Jongsun Park,Yin Wu,Jia Cui,Na Jia,Miaomiao Xi,Aidong Wen 대한생리학회-대한약리학회 2017 The Korean Journal of Physiology & Pharmacology Vol.21 No.3

The root bark extract of <i>Aralia taibaiensis</i> is used traditionally for the treatment of diabetes mellitus in China. The total saponin extracted from <i>Aralia Taibaiensis</i> (sAT) has effective combined antihyperglycemic and hypolipidemic activities in experimental type 2 diabetic rats. However, the active compounds have not yet been fully investigated. In the present study, we examined effects of twelve triterpenoid saponins on AMP-activated protein kinase (AMPK) activation, and found that compound 28-O-β-D-glucopyranosyl ester (AT12) significantly increased phosphorylation of AMPK and Acetyl-CoA carboxylase (ACC). AT12 effectively decreased blood glucose, triglyceride (TG), free fatty acid (FFA) and low density lipoprotein-cholesterol (LDL-C) levels in the rat model of type 2 diabetes mellitus (T2DM). The mechanism by which AT12 activated AMPK was subsequently investigated. Intracellular ATP level and oxygen consumption were significantly reduced by AT12 treatment. The findings suggested AT12 was a novel AMPK activator, and could be useful for the treatment of metabolic diseases.

Identification of AMPK activator from twelve pure compounds isolated from Aralia Taibaiensis: implication in antihyperglycemic and hypolipidemic activities

Li, Yuwen,Park, Jongsun,Wu, Yin,Cui, Jia,Jia, Na,Xi, Miaomiao,Wen, Aidong The Korean Society of Pharmacology 2017 The Korean Journal of Physiology & Pharmacology Vol.21 No.3

The root bark extract of Aralia taibaiensis is used traditionally for the treatment of diabetes mellitus in China. The total saponin extracted from Aralia Taibaiensis (sAT) has effective combined antihyperglycemic and hypolipidemic activities in experimental type 2 diabetic rats. However, the active compounds have not yet been fully investigated. In the present study, we examined effects of twelve triterpenoid saponins on AMP-activated protein kinase (AMPK) activation, and found that compound 28-O-${\beta}$-D-glucopyranosyl ester (AT12) significantly increased phosphorylation of AMPK and Acetyl-CoA carboxylase (ACC). AT12 effectively decreased blood glucose, triglyceride (TG), free fatty acid (FFA) and low density lipoprotein-cholesterol (LDL-C) levels in the rat model of type 2 diabetes mellitus (T2DM). The mechanism by which AT12 activated AMPK was subsequently investigated. Intracellular ATP level and oxygen consumption were significantly reduced by AT12 treatment. The findings suggested AT12 was a novel AMPK activator, and could be useful for the treatment of metabolic diseases.

Activation Mechanism of Protein Kinase B by DNA-dependent Protein Kinase Involved in the DNA Repair System

Yuwen Li,Longzhen Piao,Keum-Jin Yang,Sanghee Shin,Eulsoon Shin,Kyung Ah Park,Hee Sun Byun,Minho Won,Byung Lyul Choi,Hyunji Lee,Young-Rae Kim,Jang Hee Hong,Gang Min Hur,Jeong-Lan Kim,Jae Youl Cho,Jeong 한국독성학회 2008 Toxicological Research Vol.24 No.3

DNA-dependent protein kinase (DNA-PK) is involved in joining DNA double-strand breaks induced by ionizing radiation or V(D)J recombination and is activated by DNA ends and composed of a DNA binding subunit, Ku, and a catalytic subunit, DNA-PKcs. It has been suggested that DNA-PK might be 2nd upstream kinase for protein kinase B (PKB). In this report, we showed that Ser473 phosphorylation in the hydrophobic-motif of PKB is blocked in DNA-PK knockout mouse embryonic fibroblast cells (MEFs) following insulin stimulation, while there is no effect on Ser473 phosphorylation in DNA-PK wild type MEF cells. The observation is further confirmed in human glioblastoma cells expressing a mutant form of DNA-PK (M059J) and a wild-type of DNA-PK (M059K), indicating that DNA-PK is indeed important for PKB activation. Furthermore, the treatment of cells with doxorubicin, DNA-damage inducing agent, leads to PKB phosphorylation on Ser473 in control MEF cells while there is no response in DNA-PK knockout MEF cells. Together, these results proposed that DNA-PK has a potential role in insulin signaling as well as DNA-repair signaling pathway.

LETM1 is required for mitochondrial homeostasis and cellular viability

Li, Yuwen,Tran, Quangdon,Shrestha, Robin,Piao, Longzhen,Park, Sungjin,Park, Jisoo,Park, Jongsun D.A. Spandidos 2019 MOLECULAR MEDICINE REPORTS Vol.19 No.5

<P>Leucine zipper/EF-hand-containing transmembrane protein 1 (LETM1) has been identified as the gene responsible for Wolf-Hirschhorn syndrome (WHS), which is characterized by intellectual disability, epilepsy, growth delay and craniofacial dysgenesis. LETM1 is a mitochondrial inner membrane protein that encodes a homolog of the yeast protein Mdm38, which is involved in mitochondrial morphology. In the present review, the importance of LETM1 in WHS and its role within the mitochondrion was explored. LETM1 governs the mitochondrion ion channel and is involved in mitochondrial respiration. Recent studies have reported that LETM1 acts as a mitochondrial Ca<SUP>2+</SUP>/H<SUP>+</SUP> antiporter. LETM1 has also been identified as a K<SUP>+</SUP>/H<SUP>+</SUP> exchanger, and serves a role in Mg<SUP>2+</SUP> homeostasis. The function of LETM1 in mitochondria regulation is regulated by its binding partners, carboxyl-terminal modulator protein and mitochondrial ribosomal protein L36. Therefore, we describe the remarkable role of LETM1 in mitochondrial network physiology and its function in mitochondrion-mediated cell death. In the context of these findings, we suggest that the participation of LETM1 in tumorigenesis through the alteration of cancer metabolism should be investigated. This review provides a comprehensive description of LETM1 function, which is required for mitochondrial homeostasis and cellular viability.</P>

Identification of AMPK activator from twelve pure compounds isolated from Aralia Taibaiensis: implication in antihyperglycemic and hypolipidemic activities

Yuwen Li,박종선,Yin Wu,Jia Cui,Na Jia,Miaomiao Xi,Aidong Wen 대한약리학회 2017 The Korean Journal of Physiology & Pharmacology Vol.21 No.3

The root bark extract of Aralia taibaiensis is used traditionally for the treatment of diabetes mellitus in China. The total saponin extracted from Aralia Taibaiensis (sAT) has effective combined antihyperglycemic and hypolipidemic activities in experimental type 2 diabetic rats. However, the active compounds have not yet been fully investigated. In the present study, we examined effects of twelve triterpenoid saponins on AMP-activated protein kinase (AMPK) activation, and found that compound 28-O-β-D-glucopyranosyl ester (AT12) significantly increased phosphorylation of AMPK and Acetyl-CoA carboxylase (ACC). AT12 effectively decreased blood glucose, triglyceride (TG), free fatty acid (FFA) and low density lipoprotein-cholesterol (LDL-C) levels in the rat model of type 2 diabetes mellitus (T2DM). The mechanism by which AT12 activated AMPK was subsequently investigated. Intracellular ATP level and oxygen consumption were significantly reduced by AT12 treatment. The findings suggested AT12 was a novel AMPK activator, and could be useful for the treatment of metabolic diseases.

Mitochondrial Location of Severe Acute Respiratory Syndrome Coronavirus 3b Protein

Yuwen Cong,Xiaoling Yuan,Yajun Shan,Zhenyu Yao,Jianyong Li,Zhenhu Zhao,Jiapei Chen 한국분자세포생물학회 2006 Molecules and cells Vol.21 No.2