Article
Biochemistry & Molecular Biology
Guadalupe Garcia, Karina A. Mendez-Resendiz, Norma Oviedo, Janet Murbartian
Summary: PKC and PKA phosphorylation inhibit TREK-1 channels downstream of G(s) protein-coupled receptor activation in vitro. This study investigated the role of phosphorylation of TREK-1 in neuropathic pain, finding that PKC and PKA modulators can alter TREK-1 function to contribute to antiallodynia in neuropathic rats, potentially through the phosphorylation sites S300 and S333.
JOURNAL OF NEUROCHEMISTRY
(2021)
Article
Multidisciplinary Sciences
Omid Haji-Ghassemi, Yu Seby Chen, Kellie Woll, Georgina B. Gurrola, Carmen R. Valdivia, Wenxuan Cai, Songhua Li, Hector H. Valdivia, Filip Van Petegem
Summary: Calcins are peptides from scorpion venom that can cross cell membranes and target intracellular ion channels called Ryanodine Receptors (RyR). A study using cryo-electron microscopy found that imperacalcin, a type of calcin, binds to RyR and opens the channel pore, resulting in asymmetry and extended ion conduction pathways. Phosphorylation of imperacalcin by protein kinase A prevents its binding to RyR, highlighting the role of posttranslational modifications in determining the fate of a natural toxin. The structure of imperacalcin provides a template for developing analogs with potential to treat RyR-related disorders.
Article
Andrology
Kun Li, Peibei Sun, Yayan Wang, Tian Gao, Dongwang Zheng, Ajuan Liu, Ya Ni
Summary: This study revealed the interaction between Hsp90 and Cdc37 in human spermatozoa and showed that PKA and PKC signaling pathways regulate total protein threonine phosphorylation and Src phosphorylation during sperm capacitation. The results help to understand the mechanism underlying Hsp90 regulation of sperm function.
Article
Multidisciplinary Sciences
Yusuke Sakai, Haiyan Li, Hiromichi Inaba, Yuki Funayama, Erina Ishimori, Ayako Kawatake-Kuno, Hirotaka Yamagata, Tomoe Seki, Teruyuki Hobara, Shin Nakagawa, Yoshifumi Watanabe, Susumu Tomita, Toshiya Murai, Shusaku Uchida
Summary: The study explores the role of CaMKII beta in the ventral hippocampus in depression susceptibility and resilience, revealing that its modulation of TARP gamma-8 phosphorylation enhances stress resilience by increasing the expression of AMPA receptor subunit GluA1. These findings provide new insights into the molecular mechanisms underlying chronic stress-induced behavioral changes and offer strategies for preventing and treating stress-related psychiatric disorders.
Article
Biochemistry & Molecular Biology
Marie Pronot, Gwenola Poupon, Lara Pizzamiglio, Marta Prieto, Isabel Chato-Astrain, Iliona Lacagne, Lenka Schorova, Alessandra Folci, Frederic Brau, Stephane Martin
Summary: SUMOylation is a crucial post-translational modification for cell homeostasis, and disruption of SUMOylation homeostasis in neurons is associated with neurological disorders. The balance between SUMOylation and deSUMOylation of substrate proteins is maintained by a group of deSUMOylation enzymes called SENPs. The activation of type 1 mGlu1 and mGlu5 receptors bidirectionally controls the synaptic accumulation of the deSUMOylation enzyme SENP1.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Pharmacology & Pharmacy
Xuena Zhang, Yun Yue, Anshi Wu
Summary: This study aimed to investigate the impact of propofol anesthesia on spatial memory in rats and the expression or activity of EGR-1, c-Fos, PKA, and PKC. The results showed that propofol anesthesia impaired cognitive function in aged rats, and the expression levels of EGR-1, c-Fos, PKA, and PKC were significantly increased.
BRAZILIAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Alexandra Marsillo, Lovena David, Bishoy Gerges, Daniel Kerr, Rodina Sadek, Vitaliy Lasiychuk, David Salame, Youstina Soliman, Silvia Menkes, Aheli Chatterjee, Andrew Mancuso, Probal Banerjee
Summary: FXS, caused by the non-expression of the Fmr1 gene, leads to developmental disorders and abnormal behaviors mainly in males. Activation of PKCε has shown to correct abnormal behaviors in FXS mice during brain development and adulthood.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2021)
Article
Biochemistry & Molecular Biology
Siman Gao, Xiangteng Zhao, Lin Hou, Ruining Ma, Jie Zhou, Michael X. Zhu, Si-Jian Pan, Yong Li
Summary: The study reveals that PKC delta is SUMOylated at lysine 473 in its C-terminal catalytic domain, increasing its stability by inhibiting ubiquitination. Additionally, a functional interplay between phosphorylation and SUMOylation of PKC delta strengthens the kinase's function through recruitment of SUMO E2/E3 ligases and the PKC delta kinase. Furthermore, the SUMOylation of PKC delta enhances apoptotic cell death induced by H2O2 by promoting protein stability and phosphorylation through an interdependent interplay of the PTMs.
Article
Neurosciences
Yosef Avchalumov, Robert J. Oliver, Wulfran Trenet, Rocio Erandi Heyer Osorno, Britta D. Sibley, Dvijen C. Purohit, Candice Contet, Marisa Roberto, John J. Woodward, Chitra D. Mandyam
Summary: Chronic ethanol exposure was found to enhance neuronal excitability in the medial PFC (mPFC) and dentate gyms (DG), while re-exposure during protracted abstinence did not have the same effect, indicating resistance to vapor-induced effects. Molecular adaptations, including altered afterhyperpolarization and changes in the kinetics of action potentials, were identified under different conditions. Furthermore, Western blotting demonstrated alterations in phosphorylation levels of Ca2+/calmodulin-dependent protein kinase II (CaMKII) and glutamate receptor GluN2A/2B subunits, suggesting a novel relationship between these proteins and neuronal excitability in the context of moderate to severe AUD.
Article
Biochemistry & Molecular Biology
Valeria Kaltezioti, Iosifina P. Foskolou, Matthieu D. Lavigne, Elpinickie Ninou, Matina Tsampoula, Maria Fousteri, Marigoula Margarity, Panagiotis K. Politis
Summary: Prox1 is identified as a key gene regulatory factor that inhibits neurite elongation, allowing nascent neurons to find the correct position before initiating neurites and axon elongation.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Wei Dai, Mingxu Zhao, Caiyun Chen, Chang Zhou, Peng Wang, Zhilai Yang, Shan Gao, Yao Lu, Jiqian Zhang, Xuesheng Liu
Summary: The study highlights the importance of synaptic-activated CaMKII in Alzheimer's disease (AD) treatment and provides a new therapeutic strategy for AD treatment.
ACS CHEMICAL NEUROSCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Irina Schaefer, Clement Verkest, Lucas Vespermann, Thomas Mair, Hannah Voss, Nadja Zeitzschel, Stefan G. Lechner
Summary: PKA is a downstream effector of inflammatory mediators that increase pain hypersensitivity. This study investigates how PKA modulates the mechanosensitivity of the ion channel PIEZO2, which is crucial for nociceptor function. The research identifies multiple PKA phosphorylation sites on PIEZO2 and demonstrates that mutations in these sites abolish PKA-dependent modulation. The study also reveals functional differences between PIEZO1 and PIEZO2 and suggests that PIEZO2 is a polymodal mechanosensor.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Article
Neurosciences
Jaehoon Jeong, Yan Li, Katherine W. Roche
Summary: Our study revealed that Shank3 is highly phosphorylated in vitro, with serine 782 (S782) identified as a significant CaMKII phosphorylation site. CaMKII can phosphorylate Shank3 S782 in vitro and in heterologous cells. An autism-associated variant (Shank3 S685I) increases S782 phosphorylation. Eliminating Shank3 phosphorylation with a S782A mutation increases synaptic puncta size without affecting Shank3 colocalization with PSD-95 in cultured hippocampal neurons.
Article
Neurosciences
Mengnan Li, Xiaomin Zhang, Chongyang Li, Yanan Liu, Shuang Yang, Shilian Xu
Summary: The study found that GALR2 plays a crucial role in the galanin-induced analgesic effect by activating CaMKII and PKC in NAc, suggesting that GALR2 agonists may be effective therapeutic options for inflammatory pain.
FRONTIERS IN NEUROSCIENCE
(2021)
Article
Cell Biology
Tadayuki Komori, Tomoki Kuwahara, Tetta Fujimoto, Maria Sakurai, Ikuko Koyama-Honda, Mitsunori Fukuda, Takeshi Iwatsubo
Summary: Recent studies have identified Rab29 as a Rab protein phosphorylated by LRRK2 and found that it is also phosphorylated under lysosomal overload stress. The phosphorylation site is Ser185 and this phosphorylation is involved in counteracting lysosomal enlargement. PKCα and PKCδ are involved in this phosphorylation and control the lysosomal localization of Rab29.
JOURNAL OF CELL SCIENCE
(2023)
Article
Immunology
Xiu-xiu Liu, Lin Yang, Ling-xiao Shao, Yang He, Gang Wu, Yu-huan Bao, Nan-nan Lu, Dong-mei Gong, Ya-ping Lu, Tian-tian Cui, Ning-he Sun, Dan-yang Chen, Wei-xing Shi, Kohji Fukunaga, Hong-shan Chen, Zhong Chen, Feng Han, Ying-mei Lu
JOURNAL OF EXPERIMENTAL MEDICINE
(2020)
Article
Biochemistry & Molecular Biology
Yasushi Yabuki, Kazuya Matsuo, Ichiro Kawahata, Naoya Fukui, Tomohiro Mizobata, Yasushi Kawata, Yuji Owada, Norifumi Shioda, Kohji Fukunaga
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2020)
Review
Biochemistry & Molecular Biology
Ichiro Kawahata, Kohji Fukunaga
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2020)
Article
Neurosciences
Kazuya Matsuo, Yasushi Yabuki, Kohji Fukunaga
Article
Behavioral Sciences
Hidaka Haga, Ryo Yamada, Hisanao Izumi, Yasuharu Shinoda, Ichiro Kawahata, Hiroyuki Miyachi, Kohji Fukunaga
PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR
(2020)
Article
Biochemistry & Molecular Biology
Dian Yuan, An Cheng, Ichiro Kawahata, Hisanao Izumi, Jing Xu, Kohji Fukunaga
Summary: SAK3, like donepezil, shows significant effects in improving cognitive and emotional behaviors, as well as reducing oxidative stress levels in OBX mice. The antioxidative effects of SAK3 are similar to those of donepezil, suggesting they are among the neuroprotective mechanisms in AD pathogenesis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Yifei Wang, Yasuharu Shinoda, An Cheng, Ichiro Kawahata, Kohji Fukunaga
Summary: The research revealed that the interaction between FABP5 and α Syn can lead to mitochondrial dysfunction in neuronal cells, increasing the risk of PD development.
Article
Biochemistry & Molecular Biology
Gensheng Zhang, Huirong Han, Zhengbing Zhuge, Fang Dong, Shan Jiang, Wenwen Wang, Drielle D. Guimaraes, Tomas A. Schiffer, En Yin Lai, Lucas Rannier Ribeiro Antonino Carvalho, Ricardo Barbosa Lucena, Valdir A. Braga, Eddie Weitzberg, Jon O. Lundberg, Mattias Carlstrom
Summary: Boosting the nitrate-nitrite-NO pathway shows therapeutic potential in ameliorating renal and cardiovascular dysfunction induced by renal ischemia-reperfusion injury, reducing oxidative stress and injuries.
Article
Medicine, Research & Experimental
Sei Yoshida, Xiaoqiong Wei, Gensheng Zhang, Christopher L. O'Connor, Mauricio Torres, Zhangsen Zhou, Liangguang Lin, Rajasree Menon, Xiaoxi Xu, Wenyue Zheng, Yi Xiong, Edgar Otto, Chih-Hang Anthony Tang, Rui Hua, Rakesh Verma, Hiroyuki Mori, Yang Zhang, Chih-Chi Andrew Hu, Ming Liu, Puneet Garg, Jeffrey B. Hodgin, Shengyi Sun, Markus Bitzer, Ling Qi
Summary: The SEL1L-HRD1 ERAD complex is crucial for podocyte function and glomerular filtration barrier, as its deficiency affects nephrin maturation and leads to pathology in both mouse and human kidneys. This study provides insights into the pathogenesis associated with autosomal-recessive disease mutants.
JOURNAL OF CLINICAL INVESTIGATION
(2021)
Article
Biochemistry & Molecular Biology
Qingyun Guo, Ichiro Kawahata, Tomohide Degawa, Yuri Ikeda-Matsuo, Meiling Sun, Feng Han, Kohji Fukunaga
Summary: The study demonstrates that FABPs may exacerbate infarct volumes after ischemic stroke, and inhibiting FABPs can alleviate ischemic injury. MF6 inhibits FABPs and reduces inflammation-associated prostaglandin E-2 levels, potentially serving as a neuroprotective therapy for ischemic stroke.
Article
Peripheral Vascular Disease
Xiaohua Wang, Shan Jiang, Lingyan Fei, Fang Dong, Lanyu Xie, Xingyu Qiu, Yan Lei, Jie Guo, Ming Zhong, Xiaoqiu Ren, Yi Yang, Liang Zhao, Gensheng Zhang, Honghong Wang, Chun Tang, Luyang Yu, Ruisheng Liu, Andreas Patzak, Pontus B. Persson, Michael Hultstrom, Qichun Wei, En Yin Lai, Zhihua Zheng
Summary: This study found that the RhoA/ROCK pathway may play an important role in tacrolimus-induced hypertension by enhancing the vasoconstrictive effect of Ang II. Reactive oxygen species may participate in this process by activating the RhoA/ROCK pathway.
Review
Biochemistry & Molecular Biology
Qingyun Guo, Ichiro Kawahata, An Cheng, Wenbin Jia, Haoyang Wang, Kohji Fukunaga
Summary: Stroke is a leading cause of death and disability worldwide, but effective neuroprotective therapies for ischemic stroke patients are lacking. Lipids play important roles in the pathogenesis of neurological diseases, and fatty acid-binding proteins (FABPs) have been found to be involved in neurodegenerative diseases. However, FABPs' roles in ischemic stroke have received comparatively little attention. In this review, we summarize the literature on the associations between FABPs and ischemia and propose potential therapeutic targets for ischemic stroke.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Wenwen Wang, Yuanyuan Kang, Yu Jiang, Yalin Zhuang, Gensheng Zhang, Yuezhou Chen, Feng Zhou
Summary: This study reveals that low-dose mifepristone regulates AQP1 expression, increases cell permeability, and promotes angiogenesis through the MAPK signaling pathway. This provides important insights into the molecular mechanism of mifepristone as an anti-implantation contraceptive drug.
MOLECULAR BIOLOGY REPORTS
(2023)
Article
Biochemistry & Molecular Biology
Wenbin Jia, Ichiro Kawahata, An Cheng, Takuya Sasaki, Toshikuni Sasaoka, Kohji Fukunaga
Summary: We confirmed that the FABP3 inhibitor, MF1, successfully reduces nicotine-induced conditioned place preference in mice. MF1 treatment decreased CPP scores in a dose-dependent manner by inhibiting the activation of CaMKII and ERK in the nucleus accumbens and hippocampus.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Tong Guo, Xitong Wang, Gensheng Zhang, Tian Xia, Runzhi Zhu, Jinfa Tou
Summary: This study found that dihydromyricetin (DHM) could inhibit the growth and increase cellular mortality of HuH-6 and HepG2 cells. DHM also decreased intracellular ROS level and increased the expression of SOD1. Regulating the SOD1/ROS pathway to induce apoptosis may be one of the potential mechanisms of DHM as a tumor suppressor in hepatoblastoma.
FRONTIERS IN ONCOLOGY
(2023)
