Abstract Connexins are tumor suppressors, and human breast connexin 26 (Cx26) 43 (Cx43) gap junctions often down-regulated in cancer. We previously showed that Cx26 Cx43 overexpressed MDA-MB-231 cancer cells inhibited growth vivo but not two-dimensional cultures. In the current study, we show overexpression of or has tumor-suppressive properties a three-dimensional environment such they reduced anchorage-independent cell induced partial redifferentiation organoids cells. Importantly,...

We have recently shown that stimulation of endothelial cells with vascular growth factor (VEGF) induces dissociation caveolin-1 from the VEGFR-2 receptor, followed by Src family kinase-dependent tyrosine phosphorylation protein (Labrecque, L., Royal, I., Surprenant, D. S., Patterson, C., Gingras, D., and Béliveau, R. (2003) Mol. Biol. Cell 14, 334–347). In this study, we provide evidence VEGF-dependent interaction membrane-type 1 matrix metalloproteinase (MT1-MMP). This requires on 14...

Connexin43 (Cx43) has been reported to interact with caveolin (Cav)-1, but the role of this association and whether other members family bind Cx43 had yet be established. In study, we show that coimmunoprecipitates colocalizes Cav-1 Cav-2 in rat epidermal keratinocytes. The colocalization was confirmed keratinocytes from human epidermis vivo. Our mutation Far Western analyses revealed C-terminal tail is required for its Cavs Cx43/Cav-1 interaction direct. results indicate newly synthesized...

The mechanisms underlying membrane‐type‐1 matrix metalloproteinase (MT1‐MMP)‐dependent induction of cell migration were investigated. Overexpression MT1‐MMP induced a marked increase in migration, this being dependent on the presence cytoplasmic domain protein. MT1‐MMP‐dependent was inhibited by mitogen‐activated protein kinase 1 inhibitor, suggesting involvement extracellular signal‐regulated (ERK) cascade migration. Accordingly, overexpression activation ERK, process also its domain....

Connexin43 (Cx43) is known to have tumor-suppressive effects, but the underlying mechanisms are still poorly understood. In keratinocytes, we previously showed that COOH-terminal domain of Cx43 directly interacts with tumor suppressor Cav-1. We now show rat epidermal keratinocytes (REK) reduced in present features epithelial-to-mesenchymal transition and more invasive than their control counterparts, whereas overexpression inhibited 12-O-tetradecanoyl-phorbol-13-acetate (TPA)- growth factor...

Having shown that Panx1 and Panx3 are expressed in the epidermis, we investigated their distribution human skin adnexal structures cancer. Both proteins were found hair follicles, sebaceous eccrine glands, as well blood vessels. was detected punctate or diffuse intracellular labeling, while only observed staining, suggesting different functions. We also identified immunoreactive ∼70 kD species modulated during keratinocyte differentiation Panx3. Since our data indicate pannexins regulated...

To understand the role of connexin43 (Cx43) in epidermal differentiation, we reduced Cx43 levels by RNA-mediated interference knockdown and impaired its functional status overexpressing loss-of-function mutants associated with human disease oculodentodigital dysplasia (ODDD) rat keratinocytes. When expression was knocked down 50-75%, there a coordinate 55-65% reduction Cx26 level, gap junction-based dye coupling 60%, transepithelial resistance decreased. Importantly, overall growth...

Oculodentodigital dysplasia (ODDD) is a congenital autosomal dominant disorder with phenotypic variability, which has been associated mutations in the GJA1 gene encoding connexin43 (Cx43). Given that Cx43 mutants are thought to be equally co-expressed wild-type ODDD patients, it imperative examine consequence of these model systems reflect this molar ratio. To end, we used differential fluorescent protein tagging mutant and quantitatively monitor ratio mutant/wild-type within same putative...

This study aimed not only to compare the pharmacokinetics of oral and intravenous doses new water-soluble benzodiazepine, midazolam, but also effects on haemodynamics, sensorium, memory performance. Eight normal human volunteers each received a single 15 mg dose midazolam base orally intravenously in randomized sequence 2 weeks apart. Serial venous samples were obtained for 12 h after dosing. Vital signs, sensorium testing using word lists performed. Computerized non-linear least squares...

Although ischemia remains the leading cause of acute renal failure in humans, there is little information on expression and activities gelatinases kidney glomeruli during ischemia-reperfusion injury. In this study, we used a unilateral model to investigate activity ischemia. Unilateral was induced rats by vascular clamping (30 min) followed reperfusion (60 isolation glomeruli. The gelatinase proteins were determined gelatin zymography Western blotting. Gelatinase mRNA levels evaluated...

Abstract Proteolysis of extracellular matrix proteins by membrane-type 1 metalloproteinase (MT1-MMP) plays a pivotal role in tumor and endothelial cell migration. In addition to its proteolytic activity, several studies indicate that the proinvasive properties MT1-MMP also involve short cytoplasmic domain, but specific mechanisms mediating this function have yet be fully elucidated. Having previously shown serum factor sphingosine 1-phosphate stimulates promigratory through process involves...

Although there are currently 62 mutants of Cx43 (connexin43) that can cause ODDD (oculodentodigital dysplasia), only two have also been reported to palmar plantar hyperkeratosis. To determine how lead this skin disease, REKs (rat epidermal keratinocytes) were engineered express an ODDD-associated mutant always linked disease (fs260), ODDD-linked which has sometimes (fs230), (G21R, G138R), a mouse (G60S), non-disease-linked truncated is trapped in the endoplasmic reticulum (Δ244*) or...

Abstract Rhabdomyosarcoma (RMS), the most common soft tissue sarcoma in children, is an aggressive cancer with a poor prognosis. Despite current management, 5-year survival rate for patients metastatic RMS ∼30%; underscoring need to develop better treatment strategies. We have recently reported that pannexin 1 (PANX1) levels are downregulated and restoring its expression inhibits progression. Here, we surveyed characterized molecular changes induced by PANX1 re-expression RMS. cataloged...

Pannexin 1 (Panx1) and 3 (Panx3) are single membrane channels recently implicated in myogenic commitment, as well myoblast proliferation differentiation vitro. However, their expression patterns during skeletal muscle development regeneration had yet to be investigated. Here, we show that Panx1 levels increase becoming highly expressed together with Panx3 adult muscle. In mice, were differentially fast‐ slow‐twitch muscles. We also report Panx1/PANX1 Panx3/PANX3 co‐expressed mouse human...

Rhabdomyosarcoma (RMS) is an aggressive soft tissue sarcoma of childhood thought to arise from impaired differentiation skeletal muscle progenitors. We have recently identified Pannexin 1 (PANX1) channels as a novel regulator myogenesis. In the present study, we determined that PANX1 transcript and protein levels are down-regulated in embryonal (eRMS) alveolar RMS (aRMS) patient-derived cell lines primary tumor specimens compared differentiated myoblasts tissue, respectively. While not...

Premorbid substance use is widely recognized as a crucial factor in early psychosis. We explored the effects of childhood/adolescent adversity on premorbid tobacco, alcohol, and cannabis use. hypothesized that childhood would be associated with an increased likelihood use, amount intake, cannabis. analysed which domains have greatest impact.First-episode psychosis patients were enrolled from six inpatient psychiatric units Atlanta, Georgia Washington, D.C. was thoroughly measured, rated...

Abstract Background Duchenne muscular dystrophy (DMD) is associated with impaired muscle regeneration, progressive weakness, damage, and wasting. While the cause of DMD an X-linked loss function mutation in gene encoding dystrophin, exact mechanisms that perpetuate disease progression are unknown. Our laboratory has demonstrated pannexin 1 (Panx1 rodents; PANX1 humans) critical for development, strength, regeneration male skeletal muscle. In normal muscle, Panx1 part a multiprotein complex...