A5071479905- Connexins and lens biology
- Ion channel regulation and function
- Biochemical effects in animals
- Salmonella and Campylobacter epidemiology
- interferon and immune responses
- Heme Oxygenase-1 and Carbon Monoxide
- Nicotinic Acetylcholine Receptors Study
- Vibrio bacteria research studies
- Ubiquitin and proteasome pathways
- Antibiotic Resistance in Bacteria
- Antimicrobial Resistance in Staphylococcus
- Protein Degradation and Inhibitors
- Neuroscience of respiration and sleep
- NF-κB Signaling Pathways
- Cardiovascular, Neuropeptides, and Oxidative Stress Research
- Cell death mechanisms and regulation
- Ion Transport and Channel Regulation
- Ion Channels and Receptors
- Bacterial biofilms and quorum sensing
- PI3K/AKT/mTOR signaling in cancer
- Fecal contamination and water quality
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- GDF15 and Related Biomarkers
- Blood Coagulation and Thrombosis Mechanisms
- Immune Response and Inflammation
Boston Biomedical Research Institute
2024
Novartis (China)
2024
National Tsing Hua University
2021-2024
Novartis (United States)
2016-2024
Chi Mei Medical Center
2011-2024
Czech Academy of Sciences, Institute of Biotechnology
2024
University of Virginia
2012-2021
Carter Center
2017
Tufts Medical Center
2017
La Trobe University
2017
Abstract Pannexin 1 (PANX1) subunits form oligomeric plasma membrane channels that mediate nucleotide release for purinergic signalling, which is involved in diverse physiological processes such as apoptosis, inflammation, blood pressure regulation, and cancer progression metastasis. Here we explore the mechanistic basis PANX1 activation by using wild type engineered concatemeric channels. We find involves sequential stepwise sojourns through multiple discrete open states, each with unique...
The ATP-releasing channel Panx1 is specifically involved in blood pressure regulation by adrenergic signaling.
PARK2 is a gene implicated in disease states with opposing responses cell fate determination, yet its contribution pro-survival signaling largely unknown. Here we show that altered over third of all human cancers, and depletion results enhanced phosphatidylinositol 3-kinase/Akt (PI3K/Akt) activation increased vulnerability to PI3K/Akt/mTOR inhibitors. contributes AMPK-mediated endothelial nitric oxide synthase (eNOS), levels reactive oxygen species, concomitant increase oxidized levels,...
Rationale: Resistant hypertension is a major health concern with unknown cause. Spironolactone an effective antihypertensive drug, especially for patients resistant hypertension, and considered by the World Health Organization as essential medication. Although spironolactone can act at mineralocorticoid receptor (MR; NR3C2), there increasing evidence of MR-independent effects spironolactone. Objective: Here, we detail unexpected discovery that Panx1 (pannexin 1) channels could be relevant in...
Pannexin 1 (Panx1) is a membrane channel implicated in numerous physiological and pathophysiological processes via its ability to support release of ATP other cellular metabolites for local intercellular signaling. However, date, there has been no direct demonstration large molecule permeation the Panx1 itself, thus permselectivity different molecules remains unknown. To address this, we expressed, purified, reconstituted into proteoliposomes demonstrated that activation by caspase cleavage...
RIG-I-like receptors (RLRs) activate host innate immune responses against virus infection through recruiting the mitochondrial adaptor protein MAVS (also known as IPS1, VISA, or CARDIF). Here we show that also plays a pivotal role in maintaining intestinal homeostasis. We found knockout mice developed more severe mortality and morbidity than WT animals an experimental model of colitis. Bone marrow transplantation experiments revealed cells nonhematopoietic origin dominant protection...
Phosphoinositide 3-kinase (PI3K) activity is important for regulating cell growth, survival, and motility. We report here the identification of bromodomain-containing protein 7 (BRD7) as a p85α-interacting that negatively regulates PI3K signaling. BRD7 binds to inter-SH2 (iSH2) domain p85 through an evolutionarily conserved region located at C terminus BRD7. Via this interaction, facilitates nuclear translocation p85α. The BRD7-dependent depletion from cytosol impairs formation p85/p110...
Defective glucose uptake in adipocytes leads to impaired metabolic homeostasis and insulin resistance, hallmarks of type 2 diabetes. Extracellular ATP-derived nucleotides nucleosides are important regulators adipocyte function, but the pathway for controlled ATP release from is unknown. Here, we investigated whether Pannexin 1 (Panx1) channels control contribute homeostasis.We assessed Panx1 functionality cultured 3T3-L1 isolated murine white adipose tissue by measuring response known...
Class IA PI3Ks are activated by growth factor receptors and generate lipid second messengers that mediate downstream responses including cell growth, migration, survival. The p85 regulatory subunit of PI3K contains Src homology-2 (SH2) domains binding to tyrosine-phosphorylated or adaptor proteins facilitate localization activation at the plasma membrane. We report here persistent PKC family members phorbol ester stimulation in cells leads phosphorylation two serine residues analogous sites...
Abstract Neuropathic pain symptoms respond poorly to available therapeutics, with most treated patients reporting unrelieved and significant impairment in daily life. Here, we show that Pannexin 1 (Panx1) hematopoietic cells is required for pain-like responses following nerve injury mice, a potential therapeutic target. Panx1 knockout mice ( −/− ) were protected from hypersensitivity two sciatic models. Bone marrow transplantation studies expression of functional necessary mechanical injury....
Allergic airway inflammation is driven by type-2 CD4+ T cell inflammatory responses. We uncover an immunoregulatory role for the nucleotide release channel, Panx1, in crosstalk during disease. Inverse correlations between Panx1 and asthmatics our mouse models revealed necessity, specificity, sufficiency of cells to restrict inflammation. Global Panx1−/− mice experienced exacerbated inflammation, T-cell-specific deletion phenocopied mice. A transgenic designed re-express reversed disease...
Abstract Discovery of new small molecules that can activate distinct programmed cell death pathway is significant interest as a research tool and for the development novel therapeutics pathological conditions such cancer infectious diseases. The molecule raptinal was discovered pro-apoptotic compound rapidly trigger apoptosis by promoting release cytochrome c from mitochondria subsequently activating intrinsic apoptotic pathway. As very effective at inducing in variety different types vitro...