Article
Physiology
Chuan Jiang, Ning Dong, Jianli Feng, Maolin Hao
Summary: miR-190 plays a protective role against brain I/R damage by modulating Rho/Rho-kinase signaling.
PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Tetsu Kimura, Yuta Horikoshi, Chika Kuriyagawa, Yukitoshi Niiyama
Summary: Ischemic strokes (IS) and spinal cord injuries (SCI) are major causes of disability. The up-regulation of the RhoA/ROCK pathway contributes to neuronal apoptosis, neuroinflammation, blood-brain barrier dysfunction, astrogliosis, and axon growth inhibition in IS and SCI. Inhibiting the Rho/ROCK pathway with miRNAs alleviates apoptosis, neuroinflammation, oxidative stress, and axon growth inhibition in IS and SCI. Further studies are required to explore the significance of ncRNAs in IS and SCI and to establish new strategies for preventing and treating these devastating diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Pharmacology & Pharmacy
Iwona Baranowska, Olga Gawrys, Agnieszka Walkowska, Krzysztof H. Olszynski, Ludek Cervenka, John R. Falck, Adeniyi M. Adebesin, John D. Imig, Elzbieta Kompanowska-Jezierska
Summary: Numerous studies have shown that metabolites of arachidonic acid, specifically epoxyeicosatrienoic acids (EETs) and 20-Hydroxyeicosatetraenoic acid (20-HETE), play important roles in blood pressure regulation, vascular tone, and renal function control. In this study, the researchers tested the effectiveness of EET-A and AAA in treating spontaneously hypertensive rats (SHR) and found that the combination treatment not only reduced blood pressure but also increased nitric oxide levels.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Physiology
Agnieszka Walkowska, Ludek Cervenka, John D. Imig, John R. Falck, Janusz Sadowski, Elzbieta Kompanowska-Jezierska
Summary: The study demonstrated that in spontaneously hypertensive rats, both EET-A and AAA induced renal vasodilation but did not show additive effects. Both agents have a definite therapeutic potential for hypertension and deserve further experimental and clinical testing for novel antihypertensive therapy.
FRONTIERS IN PHYSIOLOGY
(2021)
Review
Oncology
Ammad Ahmad Farooqi, Rabbia Zahid, Humaira Naureen, Rukset Attar, Maria Gazouli, Rossana Berardi, Jolanta Szelachowska, Rafal Matkowski, Edyta Pawlak
Summary: Recent breakthroughs in high-throughput technologies have provided insights into the regulatory role of rho-associated protein kinases (ROCKs) in cancer through long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs). These findings highlight the pleiotropic modulation of ROCK1/2 by lncRNAs and circRNAs in multistep cancer progression.
Article
Cell Biology
Huizhu Zhang, Honghong He, Yan Cui, Sijiu Yu, Shijie Li, Seth Yaw Afedo, Yali Wang, Xuefeng Bai, Junfeng He
Summary: This study demonstrated that both HIF-1 alpha and HO-1 are involved in the proliferation and apoptosis of PASMCs, with HO-1 playing a crucial role in inhibiting yak PASMCs proliferation, while HIF-1 alpha promoting hypoxia-induced yak PASMCs proliferation.
CELLULAR SIGNALLING
(2021)
Article
Multidisciplinary Sciences
Mengwei Li, Limei Zhang, Xinyan Liu, Guoqiang Wang, Jian Lu, Jifeng Guo, Hongjie Wang, Jinpeng Xu, Yi Zhang, Na Li, You Zhou
Summary: This study found that low-intensity exercise training can improve the heart function and structure of spontaneously hypertensive rats by inhibiting the RhoA/ROCK signaling pathway, providing further evidence for this protective effect.
SCIENTIFIC REPORTS
(2022)
Article
Neurosciences
Jing Tang, Yiang Chen, Jinyuan Li, Shuo Yan, Zenan Wang, Xinyu Deng, Ke Feng, Yanshuo Zhang, Chunrong Chen, Huixia Geng, Yanming Wang, Lai Wang
Summary: This study explores the neuroprotective effects of 14, 15-EET on mitochondrial dynamics after cerebral ischemia-reperfusion and its underlying mechanisms. The results demonstrate that 14, 15-EET can reduce neuronal apoptosis and cerebral infarction volume, protect neuronal structural integrity, and alleviate neurological impairment. Mechanistically, 14, 15-EET regulates mitochondrial division and fusion through the phosphorylation of AMPK and the upregulation of SIRT1, preserving mitochondrial dynamics and promoting neuroprotection.
CNS NEUROSCIENCE & THERAPEUTICS
(2023)
Article
Multidisciplinary Sciences
Yudai Matsuoka, Hani Al-Shareef, Mikihiko Kogo, Hirokazu Nakahara
Summary: Rac proteins play a crucial role in cancer development, with inhibition inducing apoptosis in oral squamous cell carcinoma cells of varying malignancy grades. Activation of JNK is strongly correlated with apoptosis.
Review
Genetics & Heredity
Guangzhao Guan, Richard D. D. Cannon, Dawn E. E. Coates, Li Mei
Summary: The mechanical properties of cells play an important role in tissue homeostasis and various cellular processes. These properties are determined by the cytoskeleton, which is a complex and dynamic network of microfilaments, intermediate filaments, and microtubules. The Rho-kinase/ROCK signaling pathway regulates the architecture of this cytoskeletal network, influencing cell behavior.
Article
Biochemistry & Molecular Biology
Magdalena Wujak, Christine Veith, Cheng-Yu Wu, Tessa Wilke, Zeki Ilker Kanbagli, Tatyana Novoyatleva, Andreas Guenther, Werner Seeger, Friedrich Grimminger, Natascha Sommer, Ralph Theo Schermuly, Norbert Weissmann
Summary: The study demonstrates that AK4 regulates cell proliferation and energy metabolism in pulmonary arterial smooth muscle cells. Chronic hypoxia upregulates AK4 expression via HIF-1α, and silencing AK4 reduces PASMCs viability and proliferation, while increasing mitochondrial respiration and decreasing glycolytic metabolism. This suggests the existence of an AK4-HIF-1α feedforward loop in hypoxic PASMCs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Medicine, General & Internal
Juliette Buffault, Francoise Brignole-Baudouin, Elodie Reboussin, Karima Kessal, Antoine Labbe, Stephane Melik Parsadaniantz, Christophe Baudouin
Summary: Comparing the effects of latanoprost and a Rho-kinase inhibitor on TGF-beta 2-induced glaucoma-like model revealed that the ROCKi was able to reverse the TGF-beta 2-induced cytoskeletal and ECM rearrangements, while latanoprost only affected the extracellular matrix.
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Yukiko Enomoto, Takashi Onuma, Takamitsu Hori, Kumiko Tanabe, Kyohei Ueda, Daisuke Mizutani, Tomoaki Doi, Rie Matsushima-Nishiwaki, Shinji Ogura, Hiroki Iida, Toru Iwama, Osamu Kozawa, Haruhiko Tokuda
Summary: In this study, it was found that the combination of ristocetin and CXCL12 at low doses synergistically activates human platelets via Rac and inhibits Rho/Rho-kinase activation. This provides insights into the interplay between Rac and Rho/Rho-kinase in platelet activation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cell Biology
Ya-ru Huang, Xi-xiu Xie, Jing Yang, Xiao-ying Sun, Xiao-yun Niu, Cheng-gang Yang, Ling-jie Li, Lun Zhang, Dan Wang, Chun-yu Liu, Sheng-jie Hou, Chen-yang Jiang, Yu-ming Xu, Rui-tian Liu
Summary: In this study, it was found that the levels of ArhGAP11A significantly increase in patients with AD and APP/PS1 mice. By reducing ArhGAP11A level in neurons, both AD generation and ADo neurotoxicity can be inhibited through the RhoA/ROCK/Erk signaling pathway. Furthermore, specific reduction of ArhGAP11A level significantly reduces AD production, plaque deposition, and improves neuronal damage, neuroinflammation, and cognitive deficits in APP/PS1 mice.
Review
Biochemistry & Molecular Biology
Ashwin K. Chetty, Byung Hak Ha, Titus J. Boggon
Summary: This review focuses on the signaling pathways mediated by Rho family small GTPases and the specific roles of type II PAKs. The selectivity of Rho GTPases for PAK family members and the molecular basis for substrate recognition and regulation of signaling are discussed. The cross talk between Rho family small GTPases and the involvement of PAKs in diseases are also addressed.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Pharmacology & Pharmacy
Sherif M. Shoieb, Rambabu Dakarapu, John R. Falck, Ayman O. S. El-Kadi
Summary: Synthetic analogues of 19-HETE show inhibitory effects on CYP1A1 and CYP1B1 activity through a noncompetitive mechanism, with no significant impact on CYP1A2. These analogues can effectively inhibit EROD and MROD activities in cell-based assays and human liver microsomes, presenting a potential novel therapeutic approach for cancer and cardiovascular diseases.
EUROPEAN JOURNAL OF DRUG METABOLISM AND PHARMACOKINETICS
(2021)
Article
Endocrinology & Metabolism
Kakali Ghoshal, Xiyue Li, Dungeng Peng, John R. Falck, Raghunath Reddy Anugu, Manuel Chiusa, John M. Stafford, David H. Wasserman, Roy Zent, James M. Luther, Ambra Pozzi
Summary: In this study, researchers found that the administration of a water-soluble EET analog can improve insulin signaling in a genetic model of hepatic insulin resistance. The EET analog enhances hepatic insulin signaling, decreases expression of gluconeogenic genes, and increases expression of glycogenic genes. Mechanistically, the EET analog stabilizes membrane-associated IR beta and potentiates insulin signaling.
Article
Peripheral Vascular Disease
Tamas Kriska, Anja Herrnreiter, Sandra L. Pfister, Adeniyi Adebesin, John R. Falck, William B. Campbell
Summary: The macrophage 12/15-LO pathway enhances the action of Ang II in hypertension development, mainly by promoting endothelial synthesis of a superoxide-derived TP agonist.
Article
Peripheral Vascular Disease
Kevin Agostinucci, Rebecca Hutcheson, Sakib Hossain, Jonathan Pascale, Elizabeth Villegas, Frank Zhang, Adeniyi Michael Adebesin, John R. Falck, Sachin Gupte, Victor Garcia, Michal Laniado Schwartzman
Summary: The study suggests that overexpression of Cyp4a12 in VSMC is sufficient to induce hypertension, potentially involving the activation of Rho-kinase, increased myosin light chain phosphorylation, and activation of the contractile apparatus. The 20-HETE receptor GPR75 may represent a novel target for the treatment of hypertension and associated vascular conditions.
JOURNAL OF HYPERTENSION
(2022)
Article
Pharmacology & Pharmacy
Iwona Baranowska, Olga Gawrys, Agnieszka Walkowska, Krzysztof H. Olszynski, Ludek Cervenka, John R. Falck, Adeniyi M. Adebesin, John D. Imig, Elzbieta Kompanowska-Jezierska
Summary: Numerous studies have shown that metabolites of arachidonic acid, specifically epoxyeicosatrienoic acids (EETs) and 20-Hydroxyeicosatetraenoic acid (20-HETE), play important roles in blood pressure regulation, vascular tone, and renal function control. In this study, the researchers tested the effectiveness of EET-A and AAA in treating spontaneously hypertensive rats (SHR) and found that the combination treatment not only reduced blood pressure but also increased nitric oxide levels.
FRONTIERS IN PHARMACOLOGY
(2022)
Meeting Abstract
Biochemistry & Molecular Biology
Jonathan V. Pascale, Alexandra Wolf, Melissa-Maria Kulaprathazhe, Samir Ali, Namhee Kim, Ghezal Froogh, Adeniyi M. Adebesin, John R. Falck, Michal L. Schwartzman, Victor Garcia
Article
Pharmacology & Pharmacy
Juan A. Azcona, Samantha Tang, Elizabeth Berry, Frank F. Zhang, Radha Garvey, John R. Falck, Michal Laniado Schwartzman, Tao Yi, Thomas M. Jeitner, Austin M. Guo
Summary: This study reveals that neutrophil-derived MPO and HOCl contribute to postischemic compensatory angiogenesis by activating the HIF-1α and CYP4A11 signaling pathway, leading to increased production of 20-HETE. These findings potentially identify novel therapeutic targets for the treatment of ischemia and diseases associated with abnormal angiogenesis.
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
(2022)
Article
Cardiac & Cardiovascular Systems
Bahar Tunctan, Sefika Pinar Senol, Meryem Temiz-Resitoglu, Dilsah Ezgi Yilmaz, Demet Sinem Guden, Omer Bahceli, Mehmet Furkan Horat, Seyhan Sahan-Firat, Ayse Nihal Sari, John R. Falck, Raghunath Reddy Anugu, Kafait U. Malik
Summary: By activating the GPR75 signaling pathway, 5,14-HEDGE exerts its protective effects against LPS-induced hypotension and tachycardia in arterial tissues.
JOURNAL OF CARDIOVASCULAR PHARMACOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Sailu Munnuri, John R. Falck
Summary: In this study, Iminodirhodium reactive intermediates were generated from O-tosyloximes and utilized for three challenging transformations, including remote C-H functionalization, desaturative annulation, and directed desaturation. These reactions, which have been underexplored in previous studies, were successfully achieved under mild conditions.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Meeting Abstract
Cardiac & Cardiovascular Systems
Ahmed Darwesh, Deanna Sosnowski, Robert Valencia, Anne Konkel, John Falck, Wolf-Hagen Schunck, John Seubert
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
(2022)
Article
Cell Biology
Sofia Cardenas, Cecilia Colombero, Mariana Cruz, Eduardo Mormandi, Adeniyi Michael Adebesin, John R. Falck, Susana Nowicki
Summary: The membrane receptor GPR75 plays a role in regulating the expression and transcriptional activity of androgen receptor (AR) in prostate cancer (PCa) cells mediated by 20-hydroxyeicosatetraenoic acid (20-HETE). This suggests that targeting 20-HETE/GPR75 could be a potential strategy to limit the expression of AR-driven phenotype in PCa cells.
MOLECULAR AND CELLULAR ENDOCRINOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Kathleen Lukaszewicz, John R. R. Falck, Julian Lombard
Summary: In Dahl salt-sensitive rats, impaired vascular relaxation can be restored by restoring physiological levels of angiotensin II, inhibiting 20-HETE production, or introducing a normally functioning renin allele. However, chronically low angiotensin II levels in SS rats were found to upregulate cytochrome P450-4A and increase the production of the vasoconstrictor 20-HETE. The renin-angiotensin system and the CYP4A/20-HETE pathway both contribute to vascular dysfunction in the Dahl SS rat, but they are independent of each other.
Meeting Abstract
Oncology
Jianxun Lei, Zhijun Guo, Julissa Molina-Vega, Paloma Cervantes, Swaathi Jayaraman, John R. Hawse, Carlos Perez, Juan Abrahante, Xiaojia Tang, Krishna Kalari, Jinhua Wang, John R. Falck, Carol Lange, Matthew P. Goetz, David Potter
Article
Chemistry, Multidisciplinary
Raghunath Reddy Anugu, John R. Falck
Summary: In this study, benzylic/allylic alcohols are converted to anilines and/or nitriles as well as N-heterocycles via a site-selective C(sp(2))-C(sp(3)) cleavage reaction using commercial hydroxylamine-O-sulfonic acid (HOSA) and Et3N in a simple, one-pot process. It is noteworthy that cyclic benzylic/allylic alcohols undergo bis-functionalization, leading to increased complexity and step-economy.
Meeting Abstract
Pharmacology & Pharmacy
Bahar Tunctan, Sefika Pinar Senol, Meryem Temiz-Resitoglu, Demet Sinem Guden, Omer Bahceli, Mehmet Furkan Horat, Seyhan Sahan-Firat, Ayse Nihal Sari, John R. Falck, Kafait U. Malik
BRITISH JOURNAL OF PHARMACOLOGY
(2021)
