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7. Gα12 ablation exacerbates liver steatosis and obesity by suppressing USP22/SIRT1-regulated mitochondrial respiration

Author

Kim, Tae Hyun, Yang, Yoon Mee, Han, Chang Yeob, Koo, Ja Hyun, Oh, Hyunhee, Kim, Su Sung, You, Byoung Hoon, Choi, Young Hee, Park, Tae-Sik, Lee, Chang Ho, Kurose, Hitoshi, Noureddin, Mazen, Seki, Ekihiro, Wan, Yu-Jui Yvonne, Choi, Cheol Soo, and Kim, Sang Geon

Subjects
Obesity, Digestive Diseases, Nutrition, Chronic Liver Disease and Cirrhosis, Liver Disease, Underpinning research, 2.1 Biological and endogenous factors, 1.1 Normal biological development and functioning, Aetiology, Oral and gastrointestinal, Metabolic and endocrine, Animals, Dietary Fats, Endopeptidases, Energy Metabolism, Fatty Liver, GTP-Binding Protein alpha Subunits, G12-G13, Hepatocytes, Humans, Mice, Mice, Knockout, Mitochondria, Liver, Oxygen Consumption, Signal Transduction, Sirtuin 1, Ubiquitin Thiolesterase, Fatty acid oxidation, G-proteins, Hepatology, Metabolism, Medical and Health Sciences, Immunology
Abstract

Nonalcoholic fatty liver disease (NAFLD) arises from mitochondrial dysfunction under sustained imbalance between energy intake and expenditure, but the underlying mechanisms controlling mitochondrial respiration have not been entirely understood. Heterotrimeric G proteins converge with activated GPCRs to modulate cell-signaling pathways to maintain metabolic homeostasis. Here, we investigated the regulatory role of G protein α12 (Gα12) on hepatic lipid metabolism and whole-body energy expenditure in mice. Fasting increased Gα12 levels in mouse liver. Gα12 ablation markedly augmented fasting-induced hepatic fat accumulation. cDNA microarray analysis from Gna12-KO liver revealed that the Gα12-signaling pathway regulated sirtuin 1 (SIRT1) and PPARα, which are responsible for mitochondrial respiration. Defective induction of SIRT1 upon fasting was observed in the liver of Gna12-KO mice, which was reversed by lentivirus-mediated Gα12 overexpression in hepatocytes. Mechanistically, Gα12 stabilized SIRT1 protein through transcriptional induction of ubiquitin-specific peptidase 22 (USP22) via HIF-1α increase. Gα12 levels were markedly diminished in liver biopsies from NAFLD patients. Consistently, Gna12-KO mice fed a high-fat diet displayed greater susceptibility to diet-induced liver steatosis and obesity due to decrease in energy expenditure. Our results demonstrate that Gα12 regulates SIRT1-dependent mitochondrial respiration through HIF-1α-dependent USP22 induction, identifying Gα12 as an upstream molecule that contributes to the regulation of mitochondrial energy expenditure.

Published
2018

12. Anthropogenic Perturbations of the Carbon and Nitrogen Cycles in the East Sea (Sea of Japan)

Author

Lee, Kitack, Lee, Eunil, Lee, Chang-Ho, Ip, Wing-Huen, Editor-in-Chief, Ando, Masataka, Series Editor, Chen, Chen-Tung Arthur, Series Editor, Di, Kaichang, Series Editor, Gan, Jianping, Series Editor, Liu, Philip L.-F., Series Editor, Lo, Ching-Hua, Series Editor, Slavin, James A., Series Editor, Zhang, Keke, Series Editor, Deshpande, R. D., Series Editor, Jull, A. J. Timothy, Series Editor, and Guo, Xinyu, editor

Published
2020
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31. Aspects of urinary tract infections and antimicrobial resistance in hospitalized urology patients in Asia: 10-Year results of the Global Prevalence Study of Infections in Urology (GPIU)

Author

Nikfallah, Abolghasem, Kassem, Adham Mohamad, Aljubory, Ahmed Khalil, Salman, Ahmed, Kutmanova, Ainura Zarylbekovna, Usupbaev, Akylbek Ch, Daud Natsheh, Ala Eddin, Andreychikov, Alexander Vladimirovich, Plekhanov, Alexei Yurievich, Vinokurov, Alexey Dmitrievich, Dolgiy, Alexey Alexeevitch, Taghizade Afshari, Ali, Naghoni, Ali, Dash, Amitabh, Zaitcev, Andrey Vladimirovych, Tsukanov, Anton, Dashko, Anton, Maliavin, Anton I., Ghafouri, Ardala Abdolghafouri, Ali, Arif Maqsood, Grabsky, Arthur, Rashed, Aso Omer, Bahadzor, Badrulhisham, Purnomo, Basuki B., Gadamov, Begench Gurbangeldiyevich, Azari, Behrooz Rahnavardi, Shim, Bongsuk, Berejanski, Boris Vitalyevitch, Blas, Brian Penero, Han, Chang Hee, Lee, Chang-Ho, Xu, Chao Guan, Ooi, Chong Chien, The, Chu Leong, Kim, Chul Sung, Le, Chuyen Vu, Landau, Daniel, Rauniyar, Deepak Babu, Khazaeli, Dinyar, Soebadi, Doddy M., Lim, Donghoon, Chiong, Edmund, Alexander, Egote Kofi, Kulchavenya, Ekaterina V., Draghijeva, Elisaveta Asenova, Mohamed Elsobky, Emad Rashad, Khalid, Emad Eldin, Rashed, Fahimeh Kazemi, Wu, Fiona Mei Wen, Barakaev, Firuz, Shahbazyan, Garnik, Nakad, Haitham Saeed, Tajari, Hamid Reza, Dahmash, Hani R., Pliev, Hasan S., Saloum, Hassan Mikhael, Kumon, Hiromi, Kiyota, Hiroshi, Hayami, Hiroshi, Inatomi, Hisato, Jeon, Ho Jong, Kim, Hong Bin, Lee, Hyun-Rim, Choe, Hyun-Sop, Mah, Ida Soo-fan, Aboyan, Igor Artemovich, Cho, InRae, Essilevski, Iouri M., Khosropanah, Iradj, Abdullin, Iskander Ilfakovich, Hassan, Ismail M., Palagin, Ivan S., Kaneti, Jacob, Jeong, Jae Young, Alidjanov, Jakhongir Fatikhovich, Choi, Jin-Bong, Kim, Jong Il, Prodigalidad, Jose-Vicente Tablante, Sebastian, Joseph Philipraj, Makarycheva, Julia, Kim, Jun-Mo, Oleg, Kagan Felixovich, Cho, Kang-Jun, Karthi Keyan, Tanaka, Kazushi, Lu, Kevin, Tran Ngoc, Khac Linh, Kim, Kiho, Takahashi, Koichi, Dunets, Konstantin Antonovich, Zhu, Lan Ru, Vu, Le Nguyen, Arustamov, Levon Dm, Sinyakova, Liubov Alexandrovna, Barashova, Lyidmila Pavlovna, Ather, M. Hammad, Yong, Ma, Waze, Madhav Harihar, Zabaneh, Maher Fawzi, Baghinia, Mahmood Reza, Panigrahi, Manoj Kumar, Tayzon, Maria Fe Raymundo, Serhal, Maroun, Moktash, Mayad Nouma, Mohammad Elsayed, Medhat Ahmad, Tahami, Mehrdad, Dan, Michael, Leh, Michael Yu, Frank, Michail, Baxi, Mihir V., Kogan, Mikhail Josefovich, Wong, Ming Kui, Habous, Mohamad Alsayed, Aslmonadi, Mohamadali, Helal, Mohamed Hani Abdulwahab, Salehi, Mohammad, Moslemi, Mohammad Kazem, Moein, Mohammad Reza, Aldahiri, Mohammad Khalil Ibrahim, Tanimura, Msasanobu, Valentinovich, Mstislav Morozov, Rafique, Muhammad, Ahmad, Mumtaz, Satyavani, Muppidi, Veeramani, Muthu Veeramani, Tabash, Nahed Ahmad Al, Alsaigh, Naimet Kamal, Altarwneh, Nayel Abdullah, Taneja, Neelam, Cayco, Nelson A., Xuong, Nguyen Dinh, Viet, Nguyen Phu, Tran, Nguyen Van, Vorobyov, Nikolay Andreevich, Junejo, Noor Nabi, Sadeghifard, Nourkhoda, Kytaibekovich, Nurbek, Zuban, Oleg Nickolay, Sunga, Paul Anthony Lugue, Tamara, Perepanova Sergeevna, Aminovich, Polvonov Abror, Gyawali, Prem Raj, Dao, Quang Oanh, Mohammed, Radman Abdullah, Taghavi, Rahim Razavi, Kapoor, Rajni, Hakimzadeh, Ramin, Singh, Rachhpal S., Raz, Raul, Gopakumarapillai, Ravisankar, Bharadwaj, Renu, aghelnezhad, Reza, Khammatov, Rinat, Salh, Riyadh Al, Gamazkov, Roman Vladislavovich, Santillan, Rosanna Tubo, Hamasuna, Ryoichi, Arasteh, Saeid, Makhsudov, Saidamin Anvarovich, Chan, Sammy KK., Lee, Sang Don, Pandey, Sanjay, Ishihara, Satoshi, Takahashi, Satoshi, Kotov, Sergey Vladislavovich, Baik, Seung, Park, Seung Chol, Lee, Seung-Ju, Eredjepov, Seydali, Habibollah, Seyed, Bhange, Shashikant R., kosugi, Shigeru, Park, Shin Jae, Lu, Shing-Hwa, Falahatkar, Siavash, Ghafouryan, Sobhan, Vladimirovna, Starodoubtsevan Nadia, Nazareth, Stephen, Chaimuangraj, Suchart, Lokwani, Sudhir Kumar, Raza, Syed Johar, Taghavi, Tahim Razavi, Qazi, Tahir Uddin, Sho, Takehiko, Perepanova, Tamara Sergeevna, Sergeeuna, Tamara Perepanova, Khan, Taskeen Ahmad, Moiseenko, Tatyana Nikolaevna, Gul, Tawiz, Lin, Teng Lung, Gaviola, Teresita Tanaglin, Kim, T.H., Wijesuriya, Thamara, Ganesan, Thirumalai, Ueda, Tomohiro, Ha, U. Sin, Allahpour, Vafa Abd, Aboyan, Vitaly Eduardovich, Startsev, Vladimir, Hasan, Waleed Ali, Falou, Walid, Mirsya, Warli Syah, Qasim, Wasim, Nakamura, Wataru, Wang, Wei, Cho, WonYeol, Huang, Xiaoming, Cao, Yanwei, Farahat, Yasser Abd Elraouf, Na, Yong Gil, Cho, Yong-Hyun, Siegel, Yoram Itchak, Moussa, Youssef, Xiangbo, Zhang, Çek, Mete, Tandoğdu, Zafer, Wagenlehner, Florian, Bjerklund-Johansen, Truls Erik, and Naber, Kurt

Published
2018
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35. Data-driven Approach to New Service Concept Design

Author

Kim, Min-Jun, Lim, Chie-Hyeon, Lee, Chang-Ho, Kim, Kwang-Jae, Choi, Seunghwan, Park, Yongsung, van der Aalst, Wil, Series editor, Mylopoulos, John, Series editor, Rosemann, Michael, Series editor, Shaw, Michael J., Series editor, Szyperski, Clemens, Series editor, Borangiu, Theodor, editor, Dragoicea, Monica, editor, and Nóvoa, Henriqueta, editor

Published
2016
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39. The Correlations between the Intensity of Histopathological Ubiquitin-Specific Protease 11 Staining and Progression of Prostate Cancer.

Author

Kim, Jae Heon, Yang, Hee Jo, Lee, Kwang Woo, Park, Jae Joon, Lee, Chang-Ho, Jeon, Youn Soo, Kim, Jae Ho, Park, Suyeon, Song, Su Jung, Lee, Ji-Hye, Moon, Ahrim, Kim, Yon Hee, and Song, Yun Seob

Subjects
DEUBIQUITINATING enzymes, PROSTATE cancer prognosis, PROSTATE cancer, PTEN protein, PROSTATE cancer patients
Abstract

Background: Ubiquitin-specific protease 11 (USP11), one of the principal phosphatase and tensin homolog (PTEN) deubiquitinases, can reserve PTEN polyubiquitination to maintain PTEN protein integrity and inhibit PI3K/AKT pathway activation. The aim of the current study was to investigate the associations between immunohistochemical USP11 staining intensities and prognostic indicators in individuals with prostate cancer. Methods: Tissue microarrays (TMAs) were performed for human prostate cancer and normal tissue (control) samples. Data on patient's age, Gleason score, plasma prostate-specific antigen (PSA) titer, disease stage, and presence of seminal vesicles, lymph nodes, and surgical margin involvement were collected. A pathologist who was blinded to the clinical outcome data scored the TMA for USP11 staining intensity as either positive or negative. Results: Cancerous tissues exhibited lower USP11 staining intensity, whereas the neighboring benign peri-tumoral tissues showed higher USP11 staining intensity. The degree of USP11 staining intensity was lower in patients with a higher PSA titer, higher Gleason score, or more advanced disease stage. Patients who showed positive USP11 staining were more likely to have more optimal clinical and biochemical recurrence-free survival statistics. Conclusions: USP11 staining intensity in patients with prostate cancer is negatively associated with several prognostic factors such as an elevated PSA titer and a high Gleason score. It also reflects both biochemical and clinical recurrence-free survival in such patients. Thus, USP11 staining is a valuable prognostic factor in patients with prostate cancer. [ABSTRACT FROM AUTHOR]

Published
2023
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