Lasp-1 has been identified as a signaling molecule that is phosphorylated upon elevation of [cAMP]i in pancreas, intestine and gastric mucosa selectively expressed cells within epithelial tissues. In the parietal cell, cAMP-dependent phosphorylation induces partial translocation lasp-1 to apically directed F-actin-rich canalicular membrane, which site active HCl secretion. an unusual modular protein contains N-terminal LIM domain, C-terminal SH3 domain two internal nebulin repeats....

ABSTRACT Lasp-1 is a unique LIM and src homology 3 (SH3) domain-containing protein that was initially identified as 40 kDa cAMP-dependent phosphoprotein in the HCl-secreting gastric parietal cell. Because cAMP potent stimulator of cell acid secretion, we have hypothesized changes lasp-1 phosphorylation might be involved regulation ion transport-related activities, perhaps by modulating interactions among cytoskeletal and/or vesicle-associated proteins. In this study, demonstrate secretory...

Huntingtin interacting protein 1 related (Hip1r) is an F-actin– and clathrin-binding involved in vesicular trafficking. In this study, we demonstrate that Hip1r abundantly expressed the gastric parietal cell, predominantly localizing with F-actin to canalicular membranes. may provide a critical function vivo, as demonstrated by extensive changes cells epithelium Hip1r-deficient mice. Electron microscopy revealed abnormal apical membranes loss of tubulovesicles mutant cells, suggesting...

Skin serves not only as a protective barrier to microbial entry into the body but also an immune organ. The outer layer, epidermis, is composed predominantly of keratinocytes, which can be stimulated produce proinflammatory mediators. Although some inflammation useful defend against infection, excessive or persistent lead development inflammatory skin diseases, such psoriasis, common disorder affecting approximately 2% US population. We have previously found that phosphatidylglycerol (PG)...

Lasp-1 (LIM and SH3 domain protein 1) is a multidomain actin-binding that differentially expressed within epithelial tissues brain. In the gastric mucosa, highly in HCl-secreting parietal cell, where it prominently localized F-actin-rich subcellular regions. Histamine-induced elevation of cell [cAMP]i increases phosphorylation, which correlated with activation HCl secretion. To determine whether involved regulation secretion vivo, we generated murine model targeted disruption gene....

Oxidative stress contributes to inflammatory skin diseases, including psoriasis. Monomethylfumarate (MMF) is an antipsoriatic agent with a poorly understood mechanism of action. In other cell types MMF increases the expression nuclear factor erythroid-derived 2-like 2 (Nrf2), transcription that regulates cellular antioxidant responses, reduce oxidative like observed in disorders such as multiple sclerosis. We tested hypothesis enhances Nrf2 activity keratinocytes, thereby improving their...

Heterozygous endothelial nitric oxide synthase (eNOS) deficiency is associated with normal endothelium-dependent responses, however, little known regarding the mechanisms that maintain or impair function heterozygous eNOS deficiency. The goals of this study were to (1) determine mechanism(s) which serve in absence a single gene; and (2) whether predisposes blood vessels dysfunction response high-fat diet (HFD). Responses carotid arteries examined wild-type (eNOS+/+) eNOS-deficient (eNOS+/−)...

The water and glycerol channel, aquaporin-3 (AQP3), plays an important role in the skin epidermis, with effects on hydration, permeability barrier repair wound healing; therefore, information about mechanisms regulating its expression is for a complete understanding of function physiologically disease conditions. We previously demonstrated that histone deacetylase inhibitors (HDACi) induce mRNA protein AQP3, part through p53 family, transcription factors which acetylation known to affect...

Prolonged inflammation and impaired re-epithelization are major contributing factors to chronic non-healing diabetic wounds; diabetes is also characterized by xerosis. Advanced glycation end products (AGEs), the activation of toll-like receptors (TLRs), can trigger inflammatory responses. Aquaporin-3 (AQP3) plays essential roles in keratinocyte function skin wound re-epithelialization/re-generation hydration. Suberanilohydroxamic acid (SAHA), a histone deacetylase inhibitor, mimics increased...

In order to understand the regulatory role of protein kinase C (PKC) in secretory epithelia, it is necessary identify and characterize specific downstream targets. We previously identified one such studies gastric parietal cells. This was referred as pp66 because migrated with an apparent molecular mass 66 kDa on SDS-polyacrylamide gels. The phosphorylation increased by cholinergic agonist, carbachol, PKC activator, phorbol-12-myristate-13-acetate, a calcium-independent manner. this study,...

Glycerol is used in many skin care products because it improves function. Anecdotal reports by patients on the National Psoriasis Foundation website also suggest that glycerol may be helpful for treatment of psoriasis, although to date no experimental data confirm this idea. entry into epidermal keratinocytes facilitated aquaglyceroporins like aquaporin-3 (AQP3), and its conversion phosphatidylglycerol, a lipid messenger promotes keratinocyte differentiation, requires lipid-metabolizing...

Lasp1 is an actin-binding, signaling pathway-regulated phosphoprotein that overexpressed in several cancers. siRNA knockdown cell lines retards migration, suggesting the possibility upregulation influences cancer metastasis. Herein, we utilized a recently developed gene knockout model to assess role of modulating nontransformed functions. Wound healing and tumor initiation progressed more rapidly Lasp1(-/-) mice compared with Lasp1(+/+) controls. Embryonic fibroblasts (MEFs) derived from...

Developmentally regulated brain proteins (drebrins) are highly expressed in where they may regulate actin filament formation dendritic spines. Recently, the drebrin E2 isoform was detected certain epithelial cell types including gastric parietal cell. In cells, activation of HCl secretion is correlated with and elongation within intracellular canaliculi, which sites acid secretion. The aim this study to define pattern expression gland units intact rabbit oxyntic mucosa initiate approaches...

Tumor protein D52 is expressed at relatively high levels in cells within the gastrointestinal tract that undergo classical exocytosis and overexpressed several cancers. Current evidence supports a role for regulation of vesicular trafficking. function(s) are regulated by calcium-dependent phosphorylation; however, intracellular mechanisms mediate this process not well characterized. The goal study was to identify phosphorylation site(s) characterize kinase(s) phosphorylation. Using mass...

The mitogen-activated protein (MAP) kinases and ribosomal S6 in the skeletal muscle of insulin-resistant long-term (2 6 months' duration) diabetic rats were investigated to understand further changes insulin intracellular signaling pathways that accompany diabetes. effects insulin-mimetic vanadium compounds on activity these also examined. In 2-month rats, basal activities MAP relatively unchanged, while significantly increased. Intravenous injection moderately activated both 42-kDa kinase...

IQGAPs, GTPase-activating proteins with an IQ motif, are thought to regulate many actin cytoskeleton-based activities through interactions Cdc42 and Rac. Recently, was implicated in regulation of gastric parietal cell HCl secretion, IQGAP2 immunolocalized F-actin-rich intracellular canalicular membranes isolated cells primary culture. Here we sought define distribution localization IQGAP1 major oxyntic (acid-secreting) mucosal types determine whether secretory agonists modulate these...

Our previous work shows that dioleoylphosphatidylglycerol (DOPG) accelerates corneal epithelial healing in vitro and vivo by unknown mechanisms. Prior data demonstrate DOPG inhibits toll-like receptor (TLR) activation inflammation induced microbial components (pathogen-associated molecular patterns, PAMPs) endogenous molecules upregulated psoriatic skin, which act as danger-associated patterns (DAMPs) to activate TLRs promote inflammation. In the injured cornea, sterile can result from...

Osteoporosis, low bone mass that increases fracture susceptibility, affects approximately 75 million individuals in the United States, Europe and Japan, with number of osteoporotic fractures expected to increase by more than 3-fold over next 50 years. Bone declines age, although mechanisms for this decrease are unclear. Aging enhances production reactive oxygen species, which can affect formation breakdown. The multiple sclerosis drug Tecfidera contains dimethylfumarate, is rapidly...