Article
Biochemistry & Molecular Biology
Md Masud Rana, Kota Shiozawa, Katsuyuki Mukai, Katsuhiko Takayanagi, Koichi Eguchi, Halima Sultana, Yusuke Ohsaki, Michio Komai, Hitoshi Shirakawa
Summary: The study investigated the effect of S-allyl cysteine (SAC) on testosterone production and found that SAC significantly elevated testosterone levels by activating the PKA pathway. These findings suggest that SAC could be a potential target for hypogonadism therapeutics.
Article
Endocrinology & Metabolism
Emilia Przygrodzka, Xiaoying Hou, Pan Zhang, Michele R. Plewes, Rodrigo Franco, John S. Davis
Summary: Luteinizing hormone (LH) regulates ovulation and formation of the corpus luteum, while AMP-activated protein kinase (AMPK) exerts inhibitory effects on steroidogenesis in luteal cells by modulating the actions of PKA. AMPK regulates cholesterol availability for steroidogenesis by mediating phosphorylation of hormone-sensitive lipase (HSL), in contrast to the phosphorylation effects of LH/PKA on HSL.
Article
Biology
Gary K. L. Chan, Samantha Maisel, Yeonjoo C. Hwang, Bryan C. Pascual, Rebecca R. B. Wolber, Phuong Vu, Krushna C. Patra, Mehdi Bouhaddou, Heidi L. Kenerson, Huat C. Lim, Donald Long, Raymond S. Yeung, Praveen Sethupathy, Danielle L. Swaney, Nevan J. Krogan, Rigney E. Turnham, Kimberly J. Riehle, John D. Scott, Nabeel Bardeesy, John D. Gordan
Summary: Genetic alterations that activate protein kinase A (PKA) are found in many tumor types. The downstream oncogenic signaling mechanisms of PKA activation in human cancer were explored using phosphoproteomics and kinase activity profiling. Two signaling networks, RAS/MAPK components and an AURKA/GSK3 sub-network, were identified, both affecting MYC oncoproteins. Primary mechanism of PKA effects on MYC was found to be translation, which could be blocked with the eIF4A inhibitor zotatifin, suggesting a potential treatment strategy for PKA-driven cancers.
Review
Cell Biology
Anne-Sophie Colombe, Guillaume Pidoux
Summary: The cAMP signaling pathway plays a key role in regulating cardiac function under physiological conditions, but chronic activation can be deleterious, especially post-myocardial infarction. Temporal regulation depends on the activity of ACs and phosphodiesterases, while spatial and temporal regulation is coordinated by AKAPs.
Article
Pharmacology & Pharmacy
Yan Li, Kuiliang Zhang, Jinxin Liu, Shengnan Liu, Chenzhipeng Nie, Ying Yan, Yanming Guan, Mingcong Fan, Haifeng Qian, Hao Ying, Li Wang
Summary: Geniposide has been found to reduce body temperature and cold tolerance of mice by suppressing thermogenic genes in interscapular brown adipose tissue (iBAT) and inguinal white adipose tissue (iWAT). Additionally, geniposide suppresses thermogenic capacity of adipocytes in vitro and inhibits uncoupling protein 1 (UCP1) via regulating protein kinase A (PKA) signaling.
Article
Biochemistry & Molecular Biology
Grace E. Peng, Veronica Pessino, Bo Huang, Mark von Zastrow
Summary: This study investigates how cAMP produced by endosomes regulates signaling to the nucleus, revealing that the key location-dependent step for endosome-encoded transcriptional control is the nuclear entry of cAMP-dependent protein kinase (PKA) catalytic subunits.
NATURE CHEMICAL BIOLOGY
(2021)
Article
Biology
Colin L. Welsh, Abigail E. Conklin, Lalima K. Madan
Summary: Understanding the changes in protein shape during cellular function is crucial for understanding biology. In this study, the researchers investigated the protein PKA and how its shape changes as it chemically alters other proteins. Using crystal structures of PKA, they identified regions that change shape based on interactions with ligands or other signaling proteins. These findings provide insight into PKA and protein kinase regulation, which can lead to advances in pharmacological therapies and disease biology.
Article
Cell Biology
Xiaokan Zhang, Bryan Z. Wang, Michael Kim, Trevor R. Nash, Bohao Liu, Jenny Rao, Roberta Lock, Manuel Tamargo, Rajesh Kumar Soni, John Belov, Eric Li, Gordana Vunjak-Novakovic, Barry Fine
Summary: Protein kinase A (PKA) is critical for cardiac function, but its activity is tightly regulated. In this study, we identified STK25 as a kinase of PRKAR1A, a regulatory subunit of PKA. Phosphorylation of PRKAR1A inhibits PKA activity and increases binding to the catalytic subunit. Knockout of Stk25 in mice leads to decreased Prkar1a phosphorylation, increased Pka activity, and enhanced response to beta-adrenergic stimulation. These findings suggest that STK25 acts as a negative regulator of PKA signaling through phosphorylation of PRKAR1A.
Article
Biology
Jeannette Delva-Wiley, Ese S. Ekhator, Laquaundra L. Adams, Supriya Patwardhan, Ming Dong, Robert H. Newman
Summary: The effects of oxidation on the activity of PKA-C α towards different substrates were investigated in this study. The results showed that oxidation differentially affects the activity of PKA-C α towards different substrates. This study provides novel insights into the crosstalk between redox- and phosphorylation-dependent signaling pathways mediated by PKA and lays the foundation for future studies on the role of redox-dependent modification of kinase substrate selection in physiological and pathological states.
Review
Pharmacology & Pharmacy
Edra London, Constantine A. A. Stratakis
Summary: The cAMP-dependent protein kinase (PKA) system plays a crucial role in cell signaling and is involved in cellular metabolism, emotional and stress responses, and energy homeostasis. It is regulated by neural and peripheral signals and affects various metabolic organs. Dysregulation of the PKA system can lead to metabolic diseases, and variants in PKA subunit genes are associated with Cushing syndrome. Understanding the sex differences in PKA signaling is important for understanding the physiological consequences of metabolic dysregulation and obesity. Exploring the regulation and targets of the PKA signaling pathway can offer potential therapeutic approaches for metabolic diseases.
PHARMACOLOGY & THERAPEUTICS
(2022)
Article
Biochemistry & Molecular Biology
Ikhyun Jun, Young Joon Choi, Bo-Rahm Kim, Kyoung Yul Seo, Tae-im Kim
Summary: This study discovered that activation of the ADRB2/PKA signaling pathway enhances lipid synthesis in human meibomian gland epithelial cells (HMGECs), providing a potential mechanism and therapeutic target for meibomian gland dysfunction.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Medicinal
Ernest Awoonor-Williams, Andrei A. Golosov, Viktor Hornak
Summary: Accurate estimation of cysteine residue pKa's in proteins is crucial for targeted approaches in hit discovery. Traditional in silico tools for predicting cysteine pKa's have limited accuracy compared to other residues. Comprehensive benchmark assessments for cysteine pKa predictive tools are also limited. Therefore, further development is needed for accurate estimation and application in drug discovery.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Article
Environmental Sciences
Olga Rubin, Osher Soffer, Yaniv Levy, Joseph Aizen
Summary: By monitoring the concentrations of sex hormones and blood chemistry in female green turtles, it is possible to predict their nesting activity. This study found significant changes in hormone levels and blood chemistry parameters in relation to nesting activity. These findings can help predict and prepare for nesting activities in green sea turtles, contributing to successful breeding programs.
FRONTIERS IN MARINE SCIENCE
(2023)
Article
Biology
Xihua Yue, Yi Qian, Lianhui Zhu, Bopil Gim, Mengjing Bao, Jie Jia, Shuaiyang Jing, Yijing Wang, Chuanting Tan, Francesca Bottanelli, Pascal Ziltener, Sunkyu Choi, Piliang Hao, Intaek Lee
Summary: ACBD3 may regulate KDEL receptor trafficking by modulating Arf1-dependent tubule formation. Depletion of ACBD3 leads to re-localization of KDEL receptor to the ER through accelerated retrograde trafficking. This is caused by altering KDEL receptor interaction with Protein Kinase A and Arf1/ArfGAP1, resulting in increased Arf1-GTP-dependent tubular carrier formation at the Golgi.
Article
Biology
Juan Qin, Jingfeng Zhang, Lianyun Lin, Omid Haji-Ghassemi, Zhi Lin, Kenneth J. Woycechowsky, Filip Van Petegem, Yan Zhang, Zhiguang Yuchi
Summary: This study reveals the disease mechanism of several mutations in PLN by changing its conformation and weakening its interaction with PKA, leading to the reduction of its phosphorylation level. Additionally, another regulatory peptide, called ALN, also regulates SERCA activity through a similar mechanism mediated by PKA.
Article
Nutrition & Dietetics
Tubagus Bahtiar Rusbana, Afifah Zahra Agista, Wahyu Dwi Saputra, Yusuke Ohsaki, Kouichi Watanabe, Ardy Ardiansyah, Slamet Budijanto, Takuya Koseki, Hisashi Aso, Michio Komai, Hitoshi Shirakawa
Article
Biochemistry & Molecular Biology
Md Masud Rana, Kota Shiozawa, Katsuyuki Mukai, Katsuhiko Takayanagi, Koichi Eguchi, Halima Sultana, Yusuke Ohsaki, Michio Komai, Hitoshi Shirakawa
Summary: The study investigated the effect of S-allyl cysteine (SAC) on testosterone production and found that SAC significantly elevated testosterone levels by activating the PKA pathway. These findings suggest that SAC could be a potential target for hypogonadism therapeutics.
Article
Nutrition & Dietetics
Halima Sultana, Ayaka Kato, Ai Ohashi, Rie Takashima, Tomoko Katsurai, Shoko Sato, Masafumi Monma, Yusuke Ohsaki, Tomoko Goto, Michio Komai, Hitoshi Shirakawa
Summary: PXR acts as a key regulator of defense against foreign substances and can be activated by dietary supplements, impacting drug metabolism efficiency through interactions with drugs and nutrients.
Article
Nutrition & Dietetics
Qian Xiao, Yi-Hsiu Chen, Satwika Arya Pratama, Ya-Ling Chen, Hitoshi Shirakawa, Hsiang-Chi Peng, Suh-Ching Yang
Summary: The study demonstrated that glutamine supplementation in rats with ethanol-induced liver injury could enhance muscle protein synthesis by improving intestinal health and mitigating liver damage.
Article
Nutrition & Dietetics
Afifah Zahra Agista, Tubagus Bahtiar Rusbana, Jahidul Islam, Yusuke Ohsaki, Halima Sultana, Ryota Hirakawa, Kouichi Watanabe, Tomonori Nochi, Ardiansyah, Slamet Budijanto, Suh-Ching Yang, Takuya Koseki, Hisashi Aso, Michio Komai, Hitoshi Shirakawa
Summary: The study showed that dietary FRB supplementation can promote intestinal restoration after DSS-induced colitis and reduce the development of intestinal fibrosis. FRB supplementation also decreased the severity of colitis, increased levels of anti-inflammatory cytokines, tight junction proteins, and antimicrobial proteins in the intestines.
Review
Nutrition & Dietetics
Halima Sultana, Michio Komai, Hitoshi Shirakawa
Summary: Vitamin K plays a critical role in liver diseases, particularly in conditions related to cholestasis. By modulating PXR, vitamin K may have a positive impact on cholestasis and liver fibrosis.
Article
Plant Sciences
Ardiansyah, Annisa Nada, Nuraini Tiara Indah Rahmawati, Annisa Oktriani, Wahyudi David, Rizki Maryam Astuti, Dody Dwi Handoko, Bram Kusbiantoro, Slamet Budijanto, Hitoshi Shirakawa
Summary: This study analyzed the volatile compounds and sensory profile of fermented rice bran from two cultivars in Indonesia, and measured total phenolic content and antioxidant activity. The optimal TPC and antioxidant activity were observed after 72 hours of fermentation. The volatile compounds differed significantly among varieties, and sensory analysis showed panelists could differentiate sensory profiles between samples. Fermentation may enhance the acceptance of rice bran as a functional ingredient with enhanced bioactivity for health promotion.
Article
Food Science & Technology
Amalia Mar'atun Nadhifah, Dwi Larasatie Nur Fibri, Dody Dwi Handoko, Wahyudi David, Slamet Budijanto, Hitoshi Shirakawa, Ardiansyah
Summary: This study aims to identify the volatile compounds and aroma attributes of fermented rice bran from pigmented rice. The results showed that both fermented and non-fermented rice bran contained a total of 114 volatile compounds, with various aroma attributes. The fermented rice bran had additional fermented aroma compared to the non-fermented rice bran. Additionally, there were positive correlations between the results from GC-MS and QDA. These findings suggest that fermented rice bran could be developed as a functional ingredient due to its increased volatile compounds.
CURRENT RESEARCH IN NUTRITION AND FOOD SCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Afifah Zahra Agista, Sharon Angela Tanuseputero, Takuya Koseki, Ardiansyah, Slamet Budijanto, Halima Sultana, Yusuke Ohsaki, Chiu-Li Yeh, Suh-Ching Yang, Michio Komai, Hitoshi Shirakawa
Summary: This study isolated bioactive compounds in fermented rice bran and found that tryptamine may play a key role in its anti-inflammatory function. Furthermore, the anti-inflammatory effects of tryptamine may depend on the activity of the aryl hydrocarbon receptor.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Cell Biology
Hsin-Jung Ho, Hitoshi Shirakawa
Summary: The kidney contains mitochondria that produce ATP for cellular processes, but impaired mitochondria can cause oxidative stress injury. There is increasing evidence linking oxidative stress to kidney diseases and providing insights into mitochondria-targeted therapeutics. This review integrates recent studies on oxidative stress and mitochondrial function in kidney diseases, focusing on chronic kidney disease, and identifies potential drugs that modulate mitochondrial function for clinical therapeutics.
Article
Biochemistry & Molecular Biology
Qian Xiao, Yi-Hsiu Chen, Ya-Ling Chen, Yu-Shan Chien, Li-Hsuan Hsieh, Hitoshi Shirakawa, Suh-Ching Yang
Summary: This study investigated the beneficial effects of epidermal growth factor (EGF) on muscle loss in rats with chronic ethanol feeding. The findings showed that EGF supplementation inhibited muscular protein degradation, reduced liver injuries, and altered gut microbiota composition. However, further studies are needed to confirm the improvement in muscle loss.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Nutrition & Dietetics
Takahiro Noguchi, Hideki Kitaura, Aseel Marahleh, Afifah Zahra Agista, Yusuke Ohsaki, Hitoshi Shirakawa, Itaru Mizoguchi
Summary: Fermented rice bran (FRB) serves as a supplement with anti-inflammatory properties that can mitigate osteoclastogenesis and bone resorption induced by lipopolysaccharide (LPS) by controlling TNF-a expression in macrophages and directly inhibiting osteoclast formation.
Article
Nutrition & Dietetics
Tohfa Kabir, Haruki Yoshiba, Afifah Zahra Agista, Halima Sultana, Yusuke Ohsaki, Chiu-Li Yeh, Ryota Hirakawa, Hiroko Tani, Tomoki Ikuta, Tomonori Nochi, Suh-Ching Yang, Hitoshi Shirakawa
Summary: The study found that Gnetin C, a derivative with health-promoting properties, can prevent nonalcoholic fatty liver disease (NAFLD), reduce weight gain and liver damage, and improve blood sugar and insulin sensitivity.
Article
Nutrition & Dietetics
Pei-Xin Huang, Chiu-Li Yeh, Suh-Ching Yang, Hitoshi Shirakawa, Chao-Lin Chang, Li-Hsin Chen, Yen-Shuo Chiu, Wan-Chun Chiu
Summary: This study investigated the effects of rice bran supplementation on gut microbiota and muscle mass in high-fat diet-fed mice. The results showed that rice bran improved gut barrier dysfunction and dysbiosis, and maintained muscle mass by regulating muscle atrophy-related factors.
Article
Biotechnology & Applied Microbiology
Retno Dwi Astuti, Dwi Larasatie Nur Fibri, Dody Dwi Handoko, Wahyudi David, Slamet Budijanto, Hitoshi Shirakawa, Ardiansyah
Summary: This study investigates the volatile compounds and aroma description of fermented and nonfermented rice bran. The results show that solid-state fermentation increases the volatile compounds in rice bran and enhances specific aroma attributes. This provides opportunities for the development of fermented rice bran as a functional ingredient.
FERMENTATION-BASEL
(2022)
