Article
Agriculture, Multidisciplinary
Yanan Zhao, Jing Lu, Ankang Mao, Ranran Zhang, Shuang Guan
Summary: The study demonstrated that autophagy inhibition can protect cells against alcohol-induced ferroptosis by activating the p62-Keap1-Nrf2 pathway. Inhibition of autophagy resulted in the accumulation of p62, facilitating the translocation of Nrf2 into the nucleus and upregulating the expression of its target proteins.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2021)
Article
Pharmacology & Pharmacy
Randong Yang, Shurong Ma, Ran Zhuo, Lingqi Xu, Siqi Jia, Pengcheng Yang, Ye Yao, Haibo Cao, Liya Ma, Jian Pan, Jian Wang
Summary: Autophagy has dual roles in cancer, and CYN, a natural compound, exhibits antitumor effects against NB by modulating autophagy to inhibit apoptosis. CYN may be a promising candidate for NB treatment.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Virology
Ayan K. Ghosh, Yu-Pin Su, Michael Forman, Robert F. Keyes, Brian C. Smith, Xin Hu, Marc Ferrer, Ravit Arav-Boger
Summary: A compound called ARP101 induces the SQSTM1/p62-Keap1-Nrf2 pathway to suppress HCMV replication, providing a novel antiviral strategy for HCMV treatment.
JOURNAL OF VIROLOGY
(2023)
Article
Plant Sciences
Weiwei Zhang, Xu Geng, Qing Dong, Xiuhan Li, Ping Ye, Mengyuan Lin, Bin Xu, Hong Jiang
Summary: This study investigated the mechanism of realgar-induced neurotoxicity and its effects on autophagy and the Keap1-Nrf2-ARE pathway. The results showed that arsenic from realgar accumulated in the brain and blood, leading to neuronal and synaptic damage, decreased exploratory behavior and spontaneous movement, and impaired memory ability in rats. The mechanism may involve realgar-mediated autophagy impairment and continuous activation of the Nrf2 pathway. However, the activation of the Nrf2 pathway was insufficient to counteract oxidative damage, resulting in aggravated apoptosis in the cerebral cortex.
JOURNAL OF ETHNOPHARMACOLOGY
(2023)
Article
Food Science & Technology
Fengge Wang, Miao Liu, Peng Lin, Jishui Wang, Lihua Zhang, Haiyan Zhang, Miaomiao Qu, Shuxiong Chen, Dongmei Man
Summary: Preeclampsia is a serious complication of pregnancy, with accumulation of trophoblastic reactive oxygen species and placental dysfunction as potential pathogenic bases. Astragaloside IV (AS IV), a major active component of Astragalus membranaceus, protects trophoblasts from oxidative stress-induced damage by activating the Nrf2-Keap1-p62 feedback loop.
JOURNAL OF FUNCTIONAL FOODS
(2021)
Article
Biochemistry & Molecular Biology
Masaaki Komatsu
Summary: In this review, the author discusses the history of p62 research in relation to autophagy and provides an overview of the formation, degradation, and physiological functions of the p62 body, including efficient degradation of ubiquitinated proteins and involvement in antioxidant stress response.
Article
Biology
Yuta Horie, Takafumi Suzuki, Jin Inoue, Tatsuro Iso, Geoffrey Wells, Terry W. Moore, Tsunehiro Mizushima, Albena T. Dinkova-Kostova, Takuma Kasai, Takashi Kamei, Seizo Koshiba, Masayuki Yamamoto
Summary: This study reveals that the dissociation of Keap1 from Nrf2, known as the Hinge-Latch mechanism, is triggered by Keap1-Nrf2 inhibitors and occurs during p62-mediated Nrf2 activation, rather than by electrophilic Nrf2 inducers. Insights gained from this research can be used for the development of Nrf2 activators targeting the Keap1-Nrf2 interaction.
COMMUNICATIONS BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Bin Lee, Young Hun Kim, Woori Lee, Hee Youn Choi, Jisun Lee, Jiwon Kim, Duong Ngoc Mai, Su Ful Jung, Man Sup Kwak, Jeon-Soo Shin
Summary: This study found that ubiquitin-specific protease 13 (USP13) directly binds to p62 and removes its ubiquitination at Lys7 (K7) of the PB1 domain. Furthermore, the deubiquitination of p62 by USP13 enhances its stability, promotes p62 oligomerization, and increases autophagy and degradation of Keap1, leading to activation of Nrf2. Thus, USP13 can be considered a therapeutic target for autophagy-related diseases as a deubiquitination enzyme of p62.
FREE RADICAL BIOLOGY AND MEDICINE
(2023)
Article
Plant Sciences
Yuan Meng, Rui Feng, Zhao Yang, Tingting Liu, Taoguang Huo, Hong Jiang
Summary: This study found that arsenic in realgar passes through the blood-brain barrier and accumulates in the brain, causing damage to neurons, synapses, and myelin sheaths in the cerebral cortex and a decrease in total antioxidant capacity. The specific mechanism involves the excessive activation of Nrf2 regulated by upstream signaling molecules ERK1/2 and p38 MAPK.
JOURNAL OF ETHNOPHARMACOLOGY
(2022)
Review
Cell Biology
Weiwei Zhang, Cong Feng, Hong Jiang
Summary: The Nrf2 pathway and autophagy are important intracellular defense systems in mammals, with p62 acting as a connector between the two through a positive feedback loop to enhance cellular protection. Studies have shown that the p62-activated noncanonical Nrf2 pathway is a significant marker of neurodegenerative diseases.
AGEING RESEARCH REVIEWS
(2021)
Article
Biochemistry & Molecular Biology
Shihui Guo, Aiying Zhong, Dongxu Zhang, Jiang Gao, Yingdong Ni, Ruqian Zhao, Wenqiang Ma
Summary: Ferroptosis is involved in the development of neurological disorders, and regulating ferroptosis shows potential therapeutic effects in nervous system diseases. The study identified ATP2B3 as a target protein through TMT-based proteomic analysis, and inhibiting ATP2B3 alleviated erastin-induced ferroptosis in HT-22 cells by modulating the P62-KEAP1-NRF2-HO-1 pathway. Other interventions targeting related proteins also reversed the effects of ferroptosis. Overall, this study highlights the importance of ATP2B3 inhibition in mitigating ferroptosis in HT-22 cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Food Science & Technology
Anjun Li, Shanbin Chen, Zhen Yang, Chunguang Luan, Wei Lu, Feike Hao, Youhong Tang, Xinlin Han, Deliang Wang
Summary: This study evaluated the effect of 4-Methylguaiacol (4 MG) on antioxidant capacity and explored its molecular mechanisms in autophagy and the Keap1-Nrf2 signaling pathway in vitro and in vivo. The results showed that 4 MG had strong free radical scavenging capabilities and promoted autophagy in vitro. In a mouse model, 4 MG significantly attenuated alcoholic liver injury and increased antioxidant levels.
Article
Biochemistry & Molecular Biology
Alessia Garufi, Eugenia Giorno, Maria Saveria Gilardini Montani, Giuseppa Pistritto, Alessandra Crispini, Mara Cirone, Gabriella D'Orazi
Summary: The study found that the zinc-curcumin compound can activate NRF2 and decrease the levels of Keap1, increasing cancer cell sensitivity to Zn(II)-curc-induced cell death. The crosstalk between p62/SQSTM1 and NRF2 could be therapeutically exploited to enhance cancer patient response to therapies.
Article
Biochemistry & Molecular Biology
Cheong-Yong Yun, Nahyun Choi, Jae Un Lee, Eun Jung Lee, Ji Young Kim, Won Jun Choi, Sang Ho Oh, Jong-Hyuk Sung
Summary: This study demonstrated that the marliolide derivative DMF02 can induce melanosome degradation through autophagy pathway by activating Nrf2, leading to reduced melanin pigmentation. Additionally, DMF02 was effective in reducing UVB-induced hyperpigmentation and regulating melanosome degradation via suppression of p62. These findings suggest that Nrf2 activators could be promising therapeutic agents for reducing hyperpigmentation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Meng Meng, Ying Sun, Yuhe Bai, Jin Xu, Jingge Sun, Lirong Han, Huiqing Sun, Ran Han
Summary: This manuscript aimed to investigate the immunoregulatory activity and mechanism of CMP from Pleurotus citrinopileatus mycelium. The experiment showed that CMP significantly improved the immune response in mice, as evidenced by increased auricle swelling rate, hemolysis value, phagocytic index, immune organ indices, and reduced spleen damage. CMP also modulated the immune cell subset proportions, lymphocyte proliferation, NK cell cytotoxicity, and cytokine levels. Additionally, CMP activated the p62/Keap1/Nrf2 signaling pathway, suggesting its potential as a biological immune regulating agent.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Article
Cell Biology
Tu Nguyen, Brian James Kirsch, Ryoichi Asaka, Karim Nabi, Addison Quinones, Jessica Tan, Marjorie Justine Antonio, Felipe Camelo, Ting Li, Stephanie Nguyen, Giang Hoang, Kiet Nguyen, Sunag Udupa, Christos Sazeides, Yao-An Shen, Amira Elgogary, Juvenal Reyes, Liang Zhao, Andre Kleensang, Kaisorn Lee Chaichana, Thomas Hartung, Michael J. Betenbaugh, Suely K. Marie, Jin G. Jung, Tian-Li Wang, Edward Gabrielson, Anne Le
Article
Biochemical Research Methods
Sunag Udupa, Stephanie Nguyen, Giang Hoang, Tu Nguyen, Addison Quinones, Khoo Pham, Ryoichi Asaka, Kiet Nguyen, Cissy Zhang, Amira Elgogary, Jin G. Jung, Qingguo Xu, Jie Fu, Ajit G. Thomas, Takashi Tsukamoto, Justin Hanes, Barbara S. Slusher, ArthurJ L. Cooper, Anne Le
Article
Geriatrics & Gerontology
Lina Ma, Lolita S. Nidadavolu, Huanle Yang, Jackie Langdon, Reyhan Westbrook, Benjamin M. W. Tsui, Taek-Soo Lee, Jared Hinson, Shizhang Ling, Ruth Marx-Rattner, Yuqiong Wu, Tu Nguyen, Jessica Tan, Mohammed Khadeer, Ruin Moaddel, Anne Le, Jeremy D. Walston, Peter M. Abadir
Summary: Selective knockdown of IL-6 in a frail mouse with chronic inflammation can reverse some changes associated with chronic inflammation, but it also leads to higher mortality.
JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES
(2021)
Article
Medicine, Research & Experimental
Reyhan Westbrook, Tae Chung, Jacqueline Lovett, Chris Ward, Humberto Joca, Huanle Yang, Mohammed Khadeer, Jing Tian, Qian-Li Xue, Anne Le, Luigi Ferrucci, Ruin Moaddel, Rafa de Cabo, Ahmet Hoke, Jeremy Walston, Peter M. Abadir
Article
Biochemical Research Methods
Giang Hoang, Cissy Zhang, Nabeel Attarwala, Jin G. Jung, Arthur J. L. Cooper, Anne Le
Summary: Recent metabolomic studies have revealed the existence of metabolic cycles involving glucose-NAAG-glutamate, glutamine-lactate-glucose, and glutamate-GABA-succinate in cancer cells. These cycles play crucial roles in storing carbon sources within oncogenic cells, impacting cell metabolism and potential therapeutic targets.
ANALYTICAL BIOCHEMISTRY
(2021)
Review
Biochemistry & Molecular Biology
Yao-An Shen, Chi-Long Chen, Yi-Hsuan Huang, Emily Elizabeth Evans, Chun-Chia Cheng, Ya-Jie Chuang, Cissy Zhang, Anne Le
Summary: Targeting glutamine catabolism for cancer therapy has gained research attention, with focus on inhibiting catalytic enzymes like GLS. However, resistance to treatments targeting glutaminolysis has been observed, leading to the development of combination therapies as a potential solution.
CURRENT OPINION IN CHEMICAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Arianna F. Anzmann, Olivia L. Sniezek, Alexandra Pado, Veronica Busa, Frederic M. Vaz, Simion D. Kreimer, Lauren R. DeVine, Robert N. Cole, Anne Le, Brian J. Kirsch, Steven M. Claypool, Hilary J. Vernon
Summary: In a new HEK293-based tafazzin-deficiency model, complex I (CI) and PARL were found to be altered, leading to decreased levels of specific CI subunits and assembly factor. Remediation of these defects with pharmacologic agents SS-31 and bromoenol lactone enhances understanding of the cardiac pathology of BTHS.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Cell Biology
Tu Nguyen, Mei Zheng, Maura Knapp, Nikola Sladojevic, Qin Zhang, Lizhuo Ai, Devin Harrison, Anna Chen, Albert Sitikov, Le Shen, Frank J. Gonzalez, Qiong Zhao, Yun Fang, James J. K. Liao, Rongxue Wu
Summary: The decline in endothelial ARNT expression contributes to the suppressed angiogenic phenotype in diabetic mice. The cytoprotective effect of ARNT in endothelial cells is partially mediated by declines in ROS production.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Biochemical Research Methods
Shenghao Guo, Cissy Zhang, Anne Le
Summary: Single-cell metabolomics is a powerful tool for high-throughput metabolic analysis at the cellular level, with great potential in decoding cell heterogeneity and identifying cell types within colonies. The development of various equipment and techniques has made SCM analysis possible for a wide range of biological samples, leading to fruitful findings in various fields such as phytology, neurology, and oncology.
CURRENT OPINION IN BIOTECHNOLOGY
(2021)
Article
Oncology
Cissy Zhang, Addison Quinones, Anne Le
Summary: One of the defining features of cancer cells is their ability to reprogram metabolism to meet their needs. Recent research has shown that cancer cells can store vital metabolites for later use, providing new insights into potential cancer treatment strategies.
SEMINARS IN CANCER BIOLOGY
(2022)
Article
Materials Science, Biomaterials
Cissy Zhang, Giang Hoang, Nabeel Attarwala, Arthur J. L. Cooper, Ryoichi Asaka, Anne Le
Summary: The release of metabolic materials from dead cancer cells post-therapy can promote the growth of surviving cancer cells. The surviving cancer cells take up these metabolites and enhance multiple vital metabolic processes, resulting in significant growth. This phenomenon is observed only in oncogenic cells, providing opportunities for intervention in cancer cell growth.
Article
Geriatrics & Gerontology
Reyhan Westbrook, Cissy Zhang, Huanle Yang, Jing Tian, Shenghao Guo, Qian-Li Xue, Jeremy Walston, Anne Le, Peter M. Abadir
Summary: This study found that dysregulation of energy producing metabolic pathways is associated with frailty in older adults. Elevated levels of TCA cycle and glycolytic intermediates were observed in frail subjects, while the differences in ATP and other energy metabolites between young, nonfrail, and frail adults were not significant. Additionally, serum levels of neurotransmitters were significantly elevated in older adults with frailty.
JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES
(2022)
Review
Oncology
Anne Le, Sunag Udupa, Cissy Zhang
Article
Oncology
Ryoichi Asaka, Anne Le
MOLECULAR & CELLULAR ONCOLOGY
(2019)
Correction
Biochemistry & Molecular Biology
Siew Chin Chan, Chih-Wei Tung, Chia-Wei Lin, Yun-Shiuan Tung, Po-Min Wu, Pei-Hsun Cheng, Chuan-Mu Chen, Shang-Hsun Yang
FREE RADICAL BIOLOGY AND MEDICINE
(2024)
Article
Biochemistry & Molecular Biology
Suyuan Liu, Meiling Tan, Jiangxue Cai, Chenxuan Li, Miaoxin Yang, Xiaoxiao Sun, Bin He
Summary: This study reveals that the antibiotic doxycycline effectively inhibits NLRP3 inflammasome activation by targeting mitochondrial translation and mtDNA synthesis, offering potential for the treatment of NLRP3-related diseases.
FREE RADICAL BIOLOGY AND MEDICINE
(2024)
Article
Biochemistry & Molecular Biology
Hao Liu, Nana Li, Ge Kuang, Xia Gong, Ting Wang, Jun Hu, Hui Du, Minxuan Zhong, Jiashi Guo, Yao Xie, Yang Xiang, Shengwang Wu, Yiling Yuan, Xinru Yin, Jingyuan Wan, Ke Li
Summary: Protectin D1 (PTD1) improves hepatic steatosis, inflammation and fibrosis in a NASH mouse model by inhibiting the activation of TLR4 downstream signaling pathway, possibly through upregulation of IRAK-M expression, suggesting a potential new treatment for NASH.
FREE RADICAL BIOLOGY AND MEDICINE
(2024)