Review
Toxicology
Jephte Y. Akakpo, Anup Ramachandran, Steven C. Curry, Barry H. Rumack, Hartmut Jaeschke
Summary: Acetaminophen overdose can cause liver failure, and N-acetylcysteine (NAC) is the only FDA-approved antidote. However, its efficacy is decreased for late-presenting patients or large overdoses. Fomepizole has emerged as a promising candidate that protects the liver by inhibiting Cyp2E1 and JNK, and also prevents kidney damage and promotes liver regeneration. Mechanistic findings and safety profiles suggest that fomepizole may be a useful adjunct to NAC in treating acetaminophen overdose, and clinical trials are warranted to support this hypothesis.
ARCHIVES OF TOXICOLOGY
(2022)
Article
Pharmacology & Pharmacy
Fang Liu, Yan Liu, Qifeng Peng, Guodong Wang, Qing Tan, Zhongyue Ou, Qishan Xu, Chixiang Liu, Daming Zuo, Jianbo Zhao
Summary: This study revealed that creatinine is closely related to drug-induced liver injury and exacerbates APAP-induced hepatocyte death by promoting the production and activation of reactive oxygen species and c-Jun N-terminal kinase.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Medicine, Research & Experimental
Khairy A. Ibrahim, Hala A. Abdelgaid, Mohammed Eleyan, Rania A. Mohamed, Noha M. Gamil
Summary: The study found that resveratrol (RSV) can improve FNT-induced cardiac apoptosis. RSV alleviates cardiac oxidative damage and inflammation caused by FNT by modulating the SIRT1/c-JNK/p53 pathway and cellular redox status. RSV also improves histopathological changes in the heart.
Article
Biochemistry & Molecular Biology
Jaewon Lee, Jihoon Ha, Jun-Hyeong Kim, Dongyeob Seo, Minbeom Kim, Yerin Lee, Seong Shil Park, Dahee Choi, Jin Seok Park, Young Jae Lee, Siyoung Yang, Kyung-Min Yang, Su Myung Jung, Suntaek Hong, Seung-Hoi Koo, Yong-Soo Bae, Seong-Jin Kim, Seok Hee Park
Summary: A study has shown that the enzyme Pellino3 plays a critical role in triggering liver damage caused by acetaminophen. Mice lacking Pellino3 showed reduced liver damage, suggesting that drugs targeting Pellino3 activation could help protect the liver from APAP-induced injury.
EXPERIMENTAL AND MOLECULAR MEDICINE
(2023)
Article
Gastroenterology & Hepatology
Zhigang Fang, Hyeong-Geug Kim, Menghao Huang, Kushan Chowdhury, Ming O. Li, Suthat Liangpunsakul, X. Charlie Dong
Summary: This study demonstrates the protective role of Sesn1/2/3 in hepatic lipotoxicity-induced oxidative stress by reducing JNK phosphorylation and activity, leading to decreased lipotoxicity and oxidative stress in liver cells.
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2021)
Article
Multidisciplinary Sciences
Jiao Luo, Xiujun Tan, Ling Ye, Chenglin Wang
Summary: The study reveals that the JNK signaling pathway plays a positive role in the formation of dental papilla cell polarity, as indicated by the up-regulation of polarity-related genes and rescue effects of RhoA Q63L mutant. JNK activation is linked to polarization, migration, and differentiation of dental papilla cells, highlighting its importance in tooth development.
Article
Cardiac & Cardiovascular Systems
Jing Tan, Wei Gao, Wanchao Yang, Xianzhang Zeng, Linlin Wang, Xiaoguang Cui
Summary: JNK1 exacerbates ischemia-reperfusion injury in lung transplantation, while JNK2 alleviates it. JNK1 silencing attenuates lung graft dysfunction by inhibiting inflammation and apoptosis.
JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY
(2021)
Article
Biochemistry & Molecular Biology
Masashi Okada, Yurika Nakagawa-Saito, Yuta Mitobe, Asuka Sugai, Keita Togashi, Shuhei Suzuki, Chifumi Kitanaka
Summary: Glioma stem cells (GSCs) play a critical role in the malignancy of glioblastoma multiforme (GBM) by resisting therapy and promoting tumor initiation. This study reveals that phospholipase C (PLC) epsilon is highly expressed in GSCs and maintains their stemness and survival capacity through the activation of JNK pathway. PLC epsilon may serve as a promising therapeutic target for GSCs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Anup Ramachandran, Hartmut Jaeschke
Summary: Despite extensive research on APAP hepatotoxicity over almost 50 years, recent progress has been made in understanding the involvement of oxidative and nitrosative stress in the pathophysiology, as well as the accurate reflection of liver injury mechanisms in animals to humans. Future directions include refining the mechanistic understanding of APAP hepatotoxicity, identifying additional drugs to prevent cell death, and exploring mechanisms of regeneration and drug development to promote recovery.
ANTIOXIDANTS & REDOX SIGNALING
(2021)
Article
Oncology
Keiko Tanimura, Tadaaki Yamada, Mano Horinaka, Yuki Katayama, Sarina Fukui, Kenji Morimoto, Takayuki Nakano, Shinsaku Tokuda, Yoshie Morimoto, Masahiro Iwasaku, Yoshiko Kaneko, Junji Uchino, Kazue Yoneda, Seiji Yano, Toshiyuki Sakai, Koichi Takayama
Summary: Through activation of the JNK/c-Jun signaling, novel adaptive resistance has been identified as a key factor leading to failure of ALK-TKIs treatment, suggesting that combination therapy targeting JNK and ALK-TKIs may significantly delay regrowth of lung cancer cells and potentially improve patient outcomes.
Review
Biochemistry & Molecular Biology
Hyunwook Cho, Jung-Mi Hah
Summary: JNK3 plays a crucial role in neurodegenerative diseases, and this study summarizes the research on JNK3 inhibitors, focusing on structural and docking insights.
Article
Biochemistry & Molecular Biology
Masanori Itakura, Takeya Kubo, Akihiro Kaneshige, Hidemitsu Nakajima
Summary: GAPDH interacts with JNK and promotes its activation under oxidative stress, which is dependent on the oxidation of the active-site cysteine (Cys152) in GAPDH. Inhibition of GAPDH expression reduces JNK activation and attenuates the translocation of Bax protein to mitochondria. Therefore, GAPDH plays a significant role in the JNK signaling pathway under oxidative stress.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Anna A. Zhdankina, Dmitry I. Tikhonov, Sergey V. Logvinov, Mark B. Plotnikov, Andrei I. Khlebnikov, Nataliya G. Kolosova
Summary: Age-related macular degeneration (AMD) is the leading cause of irreversible visual impairment worldwide. JNK inhibitor IQ-1S shows potential in preventing and treating AMD, as it improves histological abnormalities associated with retinopathy in the OXYS rat model, including improved blood circulation, increased functional activity of the retinal pigment epithelium, reduced VEGF expression, and increased PEDF expression.
Article
Biochemistry & Molecular Biology
Nanami Namba, Takehiro Kuwahara, Yuki Kondo, Kumiko Fukusaki, Keishi Miyata, Yuichi Oike, Tetsumi Irie, Yoichi Ishitsuka
Summary: This study found that fasudil can protect the liver from APAP-induced injury by suppressing CHOP expression through regulating ER stress.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Igor A. Schepetkin, Oleksander S. Karpenko, Anastasia R. Kovrizhina, Liliya N. Kirpotina, Andrei I. Khlebnikov, Stepan I. Chekal, Alevtyna V. Radudik, Maryna O. Shybinska, Mark T. Quinn
Summary: The JNK family, including JNK1-3 proteins, regulates various physiological processes. The study aimed to find JNK inhibitors with high selectivity for JNK3. 26 new tryptanthrin-6-oxime analogs were synthesized and evaluated, and compounds 4d and 4e showed high selectivity for JNK3 and inhibited inflammatory responses. The results suggest the potential for developing anti-inflammatory drugs with selectivity for JNK3.