Atomoxetine and Fluoxetine Activate AMPK-ACC-CPT1 Pathway in Human SH-SY5Y and U-87 MG Cells

Songhee Jeon(Songhee Jeon),Jeong-Eun Park(Jeong-Eun Park),Young Ho Do(Young Ho Do),Renata Santos(Renata Santos ),Seong Mi Lee(Seong Mi Lee),Bung-Nyun Kim(Bung-Nyun Kim),Jae Hoon Cheong(Jae Hoon Cheong 대한신경정신의학회 2023 PSYCHIATRY INVESTIGATION Vol.20 No.3

Objective Atomoxetine and fluoxetine are psychopharmacologic agents associated with loss of appetite and weight. Adenosine monophosphate-activated protein kinase (AMPK) is the cellular energy sensor that regulate metabolism and energy, being activated by fasting and inhibited by feeding in the hypothalamus. Methods Human brain cell lines (SH-SY5Y and U-87 MG cells) were used to study the outcome of atomoxetine and fluoxetine treatment in the activity of AMPK-acetyl-CoA carboxylase (ACC)- carnitine palmitoyl transferase 1 (CPT1) pathway and upstream regulation by calcium/calmodulin-dependent kinase kinase β (CaMKKβ) using immunoblotting and CPT1 enzymatic activity measures. Results Phosphorylation of AMPK and ACC increased significantly after atomoxetine and fluoxetine treatment in the first 30-60 minutes of treatment in the two cell lines. Activation of AMPK and inhibition of ACC was associated with an increase by 5-fold of mitochondrial CPT1 activity. Although the neuronal isoform CPT1C could be detected by immunoblotting, activity was not changed by the drug treatments. In addition, the increase in phospho-AMPK and phospho-ACC expression induced by atomoxetine was abolished by treatment with STO-609, a CaMKKβ inhibitor, indicating that AMPK-ACC-CPT1 pathway is activated through CaMKKβ phosphorylation. Conclusion These findings indicate that at the cellular level atomoxetine and fluoxetine treatments may activate AMPK-ACC-CPT1 pathways through CaMKKβ in human SH-SY5Y and U-87 MG cells.

Sour cherry ameliorates hepatic lipid synthesis in high-fat diet-induced obese mice via activation of adenosine monophosphate-activated protein kinase signaling

Songhee Ahn,Minseo Kim,Hyun-Sook Kim 한국영양학회 2023 Journal of Nutrition and Health Vol.56 No.6

Purpose: Sour cherry (Prunus cerasus L.) contains abounding phytochemicals, such as polyphenols and anthocyanins, and has antioxidative effects. Adenosine monophosphateactivated protein kinase (AMPK) is a crucial regulator in enhancing the lipid metabolism. This study hypothesized that the intake of sour cherry affects AMPK signaling. Therefore, this study examined whether sour cherry regulates AMPK to balance the hepatic lipid metabolism and exert ameliorating effects. Methods: Male C57BL/6J mice had obesity induced with a 45% fat diet. The mice were divided into four groups: control (CON), high-fat diet (HFD), low percentage sour cherry powder (LSC), and high percentage sour cherry powder (HSC). The mice in the sour cherry groups were fed 1% sour cherry or 5% sour cherry in their respective diets for 12 weeks. Results: The body weight, visceral fat weight, and lipid droplet size significantly decreased in the treatment groups. The serum and hepatic triglyceride and total cholesterol levels improved significantly in the HSC group. The low-density lipoprotein cholesterol levels were also reduced significantly, whereas the high-density lipoprotein cholesterol levels were increased significantly in both treatment groups. The sterol regulator binding protein-1c and fatty acid synthase expression levels as fatty acid synthesis-related enzymes were significantly lower in the treatment groups than in the high-fat diet group. Furthermore, the adipose triglyceride lipase and hormone-sensitive lipase expression levels as lipolytic enzyme activity and AMPK/acetyl-CoA carboxylase/carnitine palmitoyltransferase-1 as fatty acid β-oxidationrelated pathway were upregulated significantly in both sour cherry groups. Conclusions: These results show that sour cherry intake improves hepatic lipid synthesis and chronic diseases by activating AMPK signaling. Therefore, this study suggests that phytochemical-rich sour cherry can be developed as a healthy functional food.

Structural Analysis of the Streptomyces avermitilis CYP107W1-Oligomycin A Complex and Role of the Tryptophan 178 Residue

Songhee HAN,Tan-Viet Pham,Joo-Hwan Kim,임영란,Hyoung-Goo Park,Gun-Su Cha,Chul-Ho Yun,Young-Jin Chun,강린우,김동학 한국분자세포생물학회 2016 Molecules and cells Vol.39 No.3

CYP107W1 from Streptomyces avermitilis is a cytochrome P450 enzyme involved in the biosynthesis of macrolide oligomycin A. A previous study reported that CYP107W1 regioselectively hydroxylated C12 of oligomycin C to produce oligomycin A, and the crystal structure of ligand free CYP107W1 was determined. Here, we analyzed the structural properties of the CYP107W1-oligomycin A complex and characterized the functional role of the Trp178 residue in CYP107W1. The crystal structure of the CYP107W1 complex with oligomycin A was determined at a resolution of 2.6 Å. Oligomycin A is bound in the substrate access channel on the upper side of the prosthetic heme mainly by hydrophobic interactions. In particular, the Trp178 residue in the active site intercalates into the large macrolide ring, thereby guiding the substrate into the correct binding orientation for a productive P450 reaction. A Trp178 to Gly mutation resulted in the distortion of binding titration spectra with oligomycin A, whereas binding spectra with azoles were not affected. The Gly178 mutant’s catalytic turnover number for the 12-hydroxylation reaction of oligomycin C was highly reduced. These results indicate that Trp178, located in the open pocket of the active site, may be a critical residue for the productive binding conformation of large macrolide substrates.

Fe(III)-doped Activated Biochar Sorbents Triggers Mitochondria Dysfunction with Oxidative Stress in Daphnia magna

Songhee LEE,Eunhea JHO,Sooim SHIN 한국생물공학회 2021 한국생물공학회 학술대회 Vol.2021 No.4

Sorbent using magnetite(Fe₃O₄) particles in the form of cartridges is frequently used material for water decontamination. However, particles can be released from the cartridge into the environment, so the sorbents can be another source of contaminants. For check the hazard of magnetite sorbent, bamboo-derived biochars and magnetite nanoparticles were prepared and used to synthesis of Fe(III)-doped activated biochar. In this study, we investigated the potential effects of magnetite sorbent-exposure on oxidative stress in Daphnia magna. Level of ROS/RNS, and amount of GSH, activity of SOD and mitochondrial complex I to IV were measured in D. magna raised with different concentrations of Fe(III)-doped sorbents. As a result, groups treated at relatively low/medium concentration of sorbent show significantly increased level of ROS/RNS than control. Moreover, activity/level of antioxidant markers were significantly reduced upon low dose of sorbent exposure. Also, activity of complex III in mitochondria exhibited markedly decreased in concentration dependent manner. It demonstrates that sorbent paralyzes the antioxidant system and also affects the function of mitochondria of D. magna.

Toxic Effects of a Synthetic Biochar-based Sorbent on Oxidative Stress of Daphnia magna

Songhee LEE,Eun Hea JHO,Sooim SHIN 한국생물공학회 2020 한국생물공학회 학술대회 Vol.2020 No.10

Effects of Plug Cell Trays, Soil and Shading Rates on Seed Germination and Seedling Growth Characteristics of Hippophae rhamnoides L.

Songhee Lee,Wonwoo Cho,Romika Chandra,Jiwon Han,Hoduck Kang 강원대학교 산림과학연구소 2020 Journal of Forest Science Vol. No.

In this study, basic data with respect to the introduction of Hipphophae rhamnoides L. and its cultivation in Korea could be obtained. According to the size of the plug cell tray, Chinese origin’s rate of seed germination was relatively high in 128 plug cell tray, and growth was vibrant in 50 plug cell tray. The germination and growth of Russian origin seeds showed that they were relatively effective in 50 plug cell tray and with respect to soil environment, TKS-2 soil with untreated shading relatively promoted both germination and growth for Chinese origin, the rate of germination was high in bed soil for horticulture and growth result was good in TKS-2 in the case of Russian origin. It was confirmed that the germination rate of Chinese origin H. rahmnoides L. was highest in untreated shading and the shoot growth was vibrant in 70% shading while the growth in roots was vibrant in the untreated shading. In the Russian origin, H. rhamnoides L. the germination rate in 30% and 70% shading was about 50% which was higher than that in the untreated shading and general growth was vibrant in 30% shading.

Road Speed Prediction Scheme Based on Machine Learning Considering Road Environment Data

Songhee Park,DoJin Choi,KyoungSoo Bok,JaeSoo Yoo 한국콘텐츠학회 2019 한국콘텐츠학회 ICCC 논문집 Vol.2019 No.12

Compensatory Effect of Mitochondrial OXPHOS in Persistent Organic Pollutants(POPs) on Liver of Mouse

Songhee LEE,Sooim SHIN 한국생물공학회 2019 한국생물공학회 학술대회 Vol.2019 No.10

Speciation of Viola albida var. takahashii based on both artificial and natural hybridization between V. albida var. albida and V. albida var. chaerophylloides

Songhee AHN,황성수 한국식물분류학회 2022 식물 분류학회지 Vol.52 No.4

The study aims are to examine the characteristics of artificial and natural hybrids between Viola albida var. albida (= albida, from below) and V. albida var. chaerophylloides (= chaerophylloides, from below), and to confirm if hybrids could be fertile and make populations in their native habitats. The 1st filial (= F1, from below) leaf shape produced by artificial crossing between albida and chaerophylloides was the same as that of V. albida var. takahashii (= takahashii, from below), and F1 bore also both chasmogamous and cleistogamous flowers. F1 seed number was 9.6 per cleistogamous pods, which was remarkably less than the average of 38.2 for albida and chaerophylloides, but the germination rate was all similar. The leaf type of self-crossed 2nd offsprings (= F2, from below) showed all leaf types found in the Viola albida complex, but the ratio of chaerophylloides leaf type was relatively low. Individuals whose F2 leaf type was restored to albida produced an average of 31.4 seeds per capsule, meaning that fertility was restored. On the other hand, individuals of F2 takahashii leaf type come to fruition a low average of 10.4 seeds per capsule, which is similar to that of takahashii. The results of crossbreeding experiment, where is their native habitats, were similar to that of laboratory. Both albida and chaerophylloids in Mt. Bulmyeong distribute extensively, but takahashii make a small population only in places where albida and chaerophylloides grow together. Summarizing the above results is suggesting that the speciation of takahashii was done by hybrid between albida and chaerophylloides, and these have been maintained with relatively small population by cleistogamous capsules.

Toxicological Effects of Polyvinyl Chloride and Low Density Polyethylene Microplastics on Territorial Organism

Songhee LEE,Eun Hea JHO,Sooim SHIN 한국생물공학회 2021 한국생물공학회 학술대회 Vol.2021 No.10

Due to the limited recovery of discarded materials and their durability, plastic debris is accumulating in the environment. The occurrence of microplastic has been studied exclusively in marine environments, but the terrestrial landmasses have not been studied. In this study, our aim was to examine potential effects of Polyvinyl chloride(PVC) and Low-density polyethylene(LDPE) microplastic in earthworm which is a representative territorial organism. To investigate the toxicological effects of microplastic, oxidative stress and mitochondrial marker were measured with different concentrations of microplastic exposure. As a result, the amounts of ROS/RNS and GSH were increased in both PVC and LDPE groups. However, ATP synthesis was decreased in the PVC treated group and increased in the LDPE treated group with a similar pattern in mitochondrial electron transfer complex activity. These results indicate that each microplastic has different oxidative mechanisms in the earthworm. For PVC, an increase in antioxidant defense led to the elimination of ROS/RNS but failed for the LDPE-treated group. These findings will provide implications for the risk of microplastic in terrestrial ecosystems.