Article
Pharmacology & Pharmacy
Jing Cheng, Fei Xue, Cheng Cheng, Wenhai Sui, Meng Zhang, Lei Qiao, Jing Ma, Xiaoping Ji, Wenqiang Chen, Xiao Yu, Bo Xi, Feng Xu, Guohai Su, Yuxia Zhao, Panpan Hao, Yun Zhang, Cheng Zhang
Summary: ADAM17 knockdown alleviates cardiac fibrosis in diabetic mice by regulating ACE2 shedding and myofibroblast transformation through the TGF-beta 1/Smad3 signaling pathway.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Eamonn F. Healy, Marko Lilic
Summary: The ACE2 receptor plays a crucial role in the cardiovascular system and is the key point of contact for the coronavirus spike protein. The shedding of ACE2 by ADAM17 and cleavage by TMPRSS2 are essential for virus entry into cells, with inflammation potentially impacting this process.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Cell Biology
Qi Chen, Yilan Li, Bike Bie, Bin Zhao, Yanxiu Zhang, Shaohong Fang, Shuijie Li, Yao Zhang
Summary: Heart failure (HF) after myocardial infarction (MI) is a prevalent disease with a poor prognosis. ADAM17 expression is increased in patients with acute MI, but its functional role in post-MI HF remains unclear. This study found that high levels of ADAM17 predict a higher incidence of post-MI HF, poorer cardiac function, and higher mortality. Animal and in vitro studies further demonstrated that ADAM17 promotes the occurrence and progression of post-MI HF.
CELL COMMUNICATION AND SIGNALING
(2023)
Article
Pharmacology & Pharmacy
Acacia White, Rohan Umesh Parekh, Drew Theobald, Pranaya Pakala, Ariel Lynn Myers, Rukiyah Van Dross, Srinivas Sriramula
Summary: Activation of kinin B1 receptor (B1R) is found to contribute to the development of endoplasmic reticulum stress (ER stress) and the initiation of unfolded protein response (UPR) in neurons, making it a key factor in the ER stress pathway.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Pharmacology & Pharmacy
Brittany Schreiber, Ankit Patel, Ashish Verma
Summary: COVID-19 is a rapidly expanding global health crisis with much unknown regarding the immunopathogenesis; ADAM17, a key protein involved in inflammation and immunosurveillance, may play a role in the disease and could be a potential therapeutic target for drug development.
AMERICAN JOURNAL OF THERAPEUTICS
(2021)
Article
Pharmacology & Pharmacy
Li-Fang Wang, Yang-Yang Sun, Qian Pan, Yi-Qing Yin, Xiao-Ming Tian, Yue Liu, Tegeleqi Bu, Qingy Zhang, Yong-An Wang, Jing Zhao, Yuan Luo
Summary: Lung ischemia-reperfusion (IR) injury depends on the loss of ACE2 and ACE2 enzyme dysfunction, while the ACE2 protectant DIZE maintains enzyme activity and protects the lungs by reducing ADAM17 levels. DIZE also inhibits oxidative and nitrosative stress, leading to reduced inflammation in lung tissue.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Eamonn F. Healy
Summary: This study investigates the relationship between ADAM17 dysregulation and the attachment of SARS-CoV-2 virus to the ACE2 receptor, and highlights the key role of Tetraspanins in this process.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Medicine, Research & Experimental
Dileep Reddy Rampa, Huiying Feng, Sivakumar Allur-Subramaniyan, Kwanseob Shim, Anton Pekcec, Dongwon Lee, Henri Doods, Dongmei Wu
Summary: This study found that BI 113823 significantly reduced liver fibrosis and portal hypertension in two established mouse models, as well as improved survival rates by inhibiting the expression of fibrotic proteins and growth factors and regulating the PI3K/Akt signaling pathway.
JOURNAL OF TRANSLATIONAL MEDICINE
(2022)
Article
Medicine, Research & Experimental
Sebastian P. Gnosa, Laia Puig Blasco, Krzysztof B. Piotrowski, Marie L. Freiberg, Simonas Savickas, Daniel H. Madsen, Ulrich Auf Dem Keller, Pauliina Kronqvist, Marie Kveiborg
Summary: Macrophages in the tumor microenvironment play a significant role in tumor progression, and ADAM17 is identified as a key mediator in controlling macrophage education. Through a paracrine EGFR ligand-chemokine feedback loop, ADAM17 facilitates cancer cells in hijacking macrophages to promote tumor progression.
Article
Biology
Kwang Su Kim, Shoya Iwanami, Takafumi Oda, Yasuhisa Fujita, Keiji Kuba, Taiga Miyazaki, Keisuke Ejima, Shingo Iwami
Summary: The duration of viral shedding depends on the balance between infection and removal of infected cells, as well as the effectiveness of antiviral drugs and the rate of virus replication. Early initiation of treatment with antiviral drugs, even with efficacy between 30-70%, can result in a prolonged duration of viral shedding in SARS-CoV-2 infection.
LIFE SCIENCE ALLIANCE
(2021)
Article
Pathology
Elizabeth S. Taglauer, Elisha M. Wachman, Lillian Juttukonda, Timothy Klouda, Jiwon Kim, Qiong Wang, Asuka Ishiyama, David J. Hackam, Ke Yuan, Hongpeng Jia
Summary: While the human placenta may be infected by SARS-CoV-2, the fetal transmission rate is low, suggesting a barrier at the maternal-fetal interface. This study found that in pregnant women with SARS-CoV-2 infection, the expression of ACE2 protein in the placenta decreased, while the activity of ADAM17 and the levels of soluble ACE2 increased.
AMERICAN JOURNAL OF PATHOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Shenghai Jiang, Hao Yang, Zhongming Sun, Yi Zhang, Yan Li, Jida Li
Summary: The activation of ADAM17 by SARS-CoV-2 infection has a dual effect on the development of the disease, increasing release of inflammatory cytokines and dysregulating ACE2. The pathologically activated ADAM17 shows superior features in regulating ACE2 expression and participating in intra cellular replication of the virus compared to the S protein. Therefore, the activation of ADAM17 may represent a weakened immune defense and altered strategies of SARS-CoV-2 infection.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2023)
Article
Oncology
Miriam Zatovicova, Ivana Kajanova, Martina Takacova, Lenka Jelenska, Olga Sedlakova, Martina Labudova, Silvia Pastorekova
Summary: Carbonic anhydrase IX (CA IX) is an enzyme involved in tumor adaptation to low oxygen levels and acidic environments. This study shows for the first time that CA IX can be shed by ADAM10 in addition to ADAM17. ADAM10 acts non-redundantly to ADAM17 in cleaving the extracellular domain of CA IX.
Review
Biochemistry & Molecular Biology
Mirelly Cunha da Silva, Vanessa Maria dos Santos, Matheus Vinicius B. da Silva, Tereza Cristina M. M. Prazeres, Maria do Socorro S. Cartagenes, Natalia Tabosa M. Calzerra, Thyago Moreira de Queiroz
Summary: This translation discusses the relationship between ADAM17 and NO formation, highlighting the important role of ADAM17 in blood pressure regulation and its implications in abnormal blood pressure and cardiac hypertrophy.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Article
Multidisciplinary Sciences
Tanja Gangnus, Bjoern B. Burckhardt
Summary: The outbreak of COVID-19 has led to increased interest in the kinin-kallikrein system, with a LC-MS/MS method established to determine kinins in respiratory lavage fluids. This method, validated according to regulatory guidelines, offers a sensitive and broad range of quantification, allowing for rapid, comprehensive, and low-volume kinin determination.
SCIENTIFIC REPORTS
(2021)
Article
Cell Biology
Blessing Ogunlade, Jessie J. Guidry, Snigdha Mukerjee, Srinivas Sriramula, Eric Lazartigues, Catalin M. Filipeanu
Summary: In this study, the researchers discovered that ACE2 is internalized and degraded in lysosomes after chronic Ang-II treatment. They identified fascin-1 as an accessory protein of ACE2 that interacts with the enzyme in an Ang-II dependent manner. Overexpression of fascin-1 attenuates the effects of Ang-II on ACE2 activity, while downregulation of fascin-1 severely decreases ACE2 enzymatic activity.
CELLULAR AND MOLECULAR NEUROBIOLOGY
(2022)
Article
Multidisciplinary Sciences
Rohan Umesh Parekh, Acacia White, Korin E. Leffler, Vinicia C. Biancardi, Jeffrey B. Eells, Abdel A. Abdel-Rahman, Srinivas Sriramula
Summary: The study reveals that the kinin B1 receptor plays a crucial role in regulating the activity of the orexin system in hypertension models, suggesting it as a potential therapeutic target for the treatment of salt-sensitive hypertension.
SCIENTIFIC REPORTS
(2021)
Article
Medicine, General & Internal
Debargha Basuli, Rohan Umesh Parekh, Acacia White, Abdullah Thayyil, Srinivas Sriramula
Summary: Despite available therapies, hypertensive kidney disease remains a significant cause of chronic kidney disease, leading to increased morbidity and mortality rates. This study reveals the importance of the B1 receptor in the development of inflammation and fibrosis in hypertensive kidney disease, providing potential targets for therapeutic interventions.
FRONTIERS IN MEDICINE
(2022)
Article
Cardiac & Cardiovascular Systems
Andrew Kisling, Shannon Byrne, Rohan U. Parekh, Deepthy Melit-Thomas, Lisandra E. de Castro Bras, Robert M. Lust, Stefan Clemens, Srinivas Sriramula, Laxmansa C. Katwa
Summary: Evidence suggests the existence of an intracardiac dopaminergic system that plays a pivotal role in regulating cardiac function and fibrosis through G-protein coupled receptors, particularly mediated by dopamine receptor 3 (D3R). The study found that D3R in cardiac fibroblasts plays a crucial role in proliferation and migration, potentially mediating cardiac fibroblast function during the wound healing response. Loss of function in D3R resulted in attenuation of both proliferation and migration in response to scratch injury, and significantly increased the expression of Col3a1 in LV fibroblasts.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2021)
Article
Clinical Neurology
Richard J. Smeyne, Jeffrey B. Eells, Debotri Chatterjee, Matthew Byrne, Shaw M. Akula, Srinivas Sriramula, Dorcas P. O'Rourke, Peter Schmidt
Summary: The study aimed to determine whether prior infection with SARS-CoV-2 increased sensitivity to a mitochondrial toxin known to induce parkinsonism. The results showed that mice recovered from SARS-CoV-2 infection showed more severe loss of substantia nigra pars compacta dopaminergic neurons after receiving the mitochondrial toxin compared to mice infected with SARS-CoV-2 or receiving the toxin alone.
MOVEMENT DISORDERS
(2022)
Article
Pharmacology & Pharmacy
Acacia White, Rohan Umesh Parekh, Drew Theobald, Pranaya Pakala, Ariel Lynn Myers, Rukiyah Van Dross, Srinivas Sriramula
Summary: Activation of kinin B1 receptor (B1R) is found to contribute to the development of endoplasmic reticulum stress (ER stress) and the initiation of unfolded protein response (UPR) in neurons, making it a key factor in the ER stress pathway.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Medicine, Research & Experimental
Shannon E. Byrne, Nandini Vishwakarma, Srinivas Sriramula, Laxmansa C. Katwa
Summary: This article reviews the research on the role of dopamine receptors in cardiac tissue, with a particular focus on D3R. It summarizes the current state of knowledge and highlights areas of research that may be lacking. Additionally, it discusses the recent findings regarding the interaction between D3R and D1R.
Article
Biochemistry & Molecular Biology
Drew Theobald, Srinivas Sriramula
Summary: Hypertension is associated with increased B1R expression and pro-inflammatory cytokines levels in neurons. Ang II upregulates B1R expression and induces neuroinflammation and oxidative stress in hypothalamic neurons. TNF, LPS, and H2O2 can upregulate B1R expression and increase oxidative stress, which can be attenuated by B1R blockade with R715. Oxidative stress is upregulated in the PVN of the brain in a DOCA-salt model of hypertension.
Article
Cardiac & Cardiovascular Systems
Mazher Mohammed, Blessing Ogunlade, Mona Elgazzaz, Clara Berdasco, Navya Lakkappa, Ioana Ghita, Jessie J. Guidry, Srinivas Sriramula, Jiaxi Xu, Luke Restivo, Michelle A. Mendiola Pla, Dawn E. Bowles, Andreas M. Beyer, Xinping Yue, Eric Lazartigues, Catalin M. Filipeanu
Summary: This study aimed to identify E3 ubiquitin ligases associated with ACE2 ubiquitination in neurogenic hypertension and establish their clinical relevance. By combining bioinformatics and proteomics, the researchers were able to identify Nedd4-2 as the first E3 ubiquitin ligase involved in ACE2 ubiquitination in Ang-II-mediated hypertension. They also demonstrated the important role of ACE2 in GABAergic neurons in maintaining inhibitory tone and regulating pre-sympathetic activity. These findings provide a new understanding of the development of neurogenic hypertension and potential therapeutic strategies. Rating: 9/10.
CARDIOVASCULAR RESEARCH
(2023)
Article
Cardiac & Cardiovascular Systems
Drew Theobald, Anand R. Nair, Srinivas Sriramula, Joseph Francis
Summary: Toll-like receptor 4 (TLR4) plays a crucial role in the innate immune response and cardiovascular diseases. This study found that cardiomyocyte-specific deletion of TLR4 provides protection against hypertension, cardiac hypertrophy, and remodeling. The results showed that in mice with cardiomyocyte-specific TLR4 knockdown, angiotensin II-induced hypertension and cardiac hypertrophy were attenuated, myocardial fibrosis was reduced, and cardiac function was improved.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2023)
Article
Cell Biology
Srinivas Sriramula, Drew Theobald, Rohan Umesh Parekh, Shaw M. Akula, Dorcas P. O'Rourke, Jeffrey B. Eells
Summary: Evidence suggests that patients with long COVID can experience neuropsychiatric, neurologic, and cognitive symptoms. An animal model using K18-hACE2 mice infected with SARS-CoV-2 demonstrates persistent effects on the brain, with increased expression of the pro-inflammatory kinin B1 receptor (B1R) and behavioral alterations such as elevated anxiety and attenuated exploratory behavior. These findings shed light on the potential mechanisms contributing to long COVID symptoms in at-risk populations and suggest that elevated B1R expression may drive the long-lasting inflammatory response associated with SARS-CoV-2 infection.