A5017265102- Cell death mechanisms and regulation
- Heat shock proteins research
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Melanoma and MAPK Pathways
- Kruppel-like factors research
- Connective Tissue Growth Factor Research
- Protein Kinase Regulation and GTPase Signaling
- PI3K/AKT/mTOR signaling in cancer
- S100 Proteins and Annexins
- FOXO transcription factor regulation
- Metabolism, Diabetes, and Cancer
- Genetic Syndromes and Imprinting
- Receptor Mechanisms and Signaling
- Ion Transport and Channel Regulation
- Chronic Kidney Disease and Diabetes
- Cancer, Hypoxia, and Metabolism
- Pancreatic function and diabetes
- Phagocytosis and Immune Regulation
- Cell Adhesion Molecules Research
- Renal and related cancers
- Ubiquitin and proteasome pathways
- TGF-β signaling in diseases
- Cytokine Signaling Pathways and Interactions
- Mitochondrial Function and Pathology
- Cancer-related gene regulation
University of Louisville
2009-2024
Hidayatullah National Law University
2022
University of Louisville Hospital
2005-2007
Zhejiang Medicine (China)
2005
Activation of the serine-threonine kinase Akt by cytokines, chemokines, and bacterial products delays constitutive neutrophil apoptosis, resulting in a prolonged inflammatory response. We showed previously that exists signaling complex with p38 MAPK, MAPK-activated protein kinase-2 (MAPKAPK-2), heat shock protein-27 (Hsp27); Hsp27 dissociates from upon activation. To better understand regulation this module, hypothesis phosphorylation regulates its interaction was tested. The present study...
Akt activation requires phosphorylation of Thr(308) and Ser(473) by 3-phosphoinositide-dependent kinase-1 2 (PDK1 PDK2), respectively. While PDK1 has been cloned sequenced, PDK2 yet to be identified. The present study shows that phosphatidylinositol 3-kinase-dependent p38 kinase regulates activity in human neutrophils. Inhibition with SB203580 inhibited following neutrophil stimulation formyl-methionyl-leucyl-phenylalanine, FcgammaR cross-linking, or 3,4,5-trisphosphate. Concentration...
Abstract Activated neutrophils play an important role in the pathogenesis of sepsis, glomerulonephritis, acute renal failure, and other inflammatory processes. The resolution neutrophil-induced inflammation relies, large part, on removal apoptotic neutrophils. Neutrophils are constitutively committed to apoptosis, but mediators, such as GM-CSF, slow neutrophil apoptosis by incompletely understood mechanisms. We addressed hypothesis that GM-CSF delays activation extracellular signal-regulated...
The present study was to investigate whether sulforaphane (SFN) can prevent diabetic nephropathy in type 1 mouse model induced by multiple low-dose streptozotocin. Diabetic and age-matched control mice were given SFN at 0.5 mg/kg body weight daily for 3 months. At the end of 3-month treatment, nephropathy, shown renal inflammation, oxidative damage, fibrosis, dysfunction, significantly prevented along with an elevation Nrf2 expression transcription diabetes/SFN group compared group. However,...
Application of doxorubicin (Dox) for the treatment cancer is restricted due to its severe side effects. We used combination strategy by combining with withaferin A (WFA) minimize ill effects Dox. Treatment various epithelial ovarian cell lines (A2780, A2780/CP70 and CaOV3) WFA Dox (WFA/DOX) showed a time- dose-dependent synergistic effect on inhibition proliferation induction death, thus reducing dosage requirement Combination resulted in significant enhancement ROS production resulting...
Formyl peptide receptor activation of three mitogen-activated protein kinase (MAPK) cascades, extracellular signal-regulated kinases (ERKs), N-terminal (JNKs), and p38 MAPK was examined in differentiated HL-60 granulocytes. FMLP stimulated a concentration- time-dependent increase ERK, JNK, activities, all which were dependent on pertussis toxin-sensitive G protein. Pharmacologic inhibitors used to examine the roles tyrosine kinases, phosphatidylinositol 3-kinase, C, phospholipase C....
We have shown previously that Akt exists in a signal complex with p38 MAPK, MAPK-activated protein kinase-2 (MK2), and heat shock 27 (Hsp27) MK2 phosphorylates on Ser-473. Additionally, dissociation of Hsp27 from Akt, prior to activation, induced polymorphonuclear leukocyte (PMN) apoptosis. However, the role regulating activation was not examined. This study tested hypothesis regulates promotes cell survival by scaffolding complex. Here we show loss Akt/Hsp27 interaction anti-Hsp27 antibody...
Mitogen-activated protein kinase (MAPK)-activated 2 (MAPKAPK2) mediates multiple p38 MAPK-dependent inflammatory responses. To define the signal transduction pathways activated by MAPKAPK2, we identified potential MAPKAPK2 substrates using a functional proteomic approach consisting of in vitro phosphorylation neutrophil lysate active recombinant separation sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and phosphoprotein identification peptide mass fingerprinting with...
In neurons, hypoxia activates intracellular death-related pathways, yet the antiapoptotic mechanisms triggered by remain unclear. RN46A neuronal cells, minimum media growth conditions induced cell death as early 12 h after cells were placed in these (i.e., removal of B-27 supplement). However, apoptosis occurred (1% O2) only 48 h, and fact reduced associated with trophic factor withdrawal. Furthermore, time-dependent increases expression platelet-derived (PDGF) B mRNA protein, well PDGF-beta...
Protein kinase B/Akt (PKB/Akt) is a member of the ACG family, which also includes protein C, that phosphorylates number 14-3-3-binding proteins. 14-3-3 regulation C activity modulated by phosphorylation. We examined hypothesis PKB/Akt interacts with and 14-3-3ζ, leading to modulation dimerization. By glutathione <i>S</i>-transferase pull-down, Akt precipitated recombinant 14-3-3ζ endogenous from HEK293 cell lysates. Recombinant active phosphorylated in an <i>in vitro</i> assay. Transfection...
Cardiotonic glycosides, like ouabain, inhibit Na + -K -ATPase. Recent evidence suggests that low molar concentrations of ouabain alter cell growth. Studies were conducted to examine the effect on Akt phosphorylation and rate proliferation in opossum kidney (OK) proximal tubule cells. Cells exposed 10 nM displayed increased Ser 473 phosphorylation, as evidenced by an increase phospho-Akt band density. Ouabain-stimulated was inhibited pretreatment with phosphatidylinositol 3-kinase (PI3K)...
Abstract The targets of the p38 MAPK pathway that mediate neutrophil functional responses are largely unknown. To identify targets, a proteomic approach was applied in which recombinant active and [32P]ATP were added to lysates from unstimulated human neutrophils. Proteins separated by two-dimensional gel electrophoresis, phosphoproteins visualized autoradiography identified MALDI-TOF. Myeloid-related protein-14 (MRP-14) as candidate substrate. MRP-14 phosphorylation confirmed an vitro...
The p38 MAPK pathway regulates multiple neutrophil functional responses via activation of the serine-threonine kinase MAPK-activated protein 2 (MAPKAPK2). To identify substrates MAPKAPK2 that mediate these responses, a proteomic approach was used in which vitro phosphorylation lysates by exogenously added active recombinant followed separation using two-dimensional electrophoresis. Peptide mass fingerprinting peptides defined MALDI-MS then utilized to phosphorylated proteins detected...
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Noncanonical roles for caspase-3 are emerging in the fields of cancer and developmental biology. However, little is known nonapoptotic functions most cell types. We have recently demonstrated a disassociation between activation execution apoptosis with accompanying cytoplasmic sequestration preserved endothelial barrier function. Therefore, we tested hypothesis that promotes integrity. Human lung microvascular cells were exposed to thrombin, stimulus, function was assessed using electric...
The serine-threonine kinase Akt regulates mesangial cell apoptosis, proliferation, and hypertrophy. To define signaling pathways in cells, we performed a functional proteomic screen for rat proteins phosphorylated by Akt. A group of chaperone proteins, heat shock protein (Hsp) 70, Hsp90α, Hsp90β, Glucose-regulated (Grp) Grp78, Grp94, disulfide isomerase (PDI) were identified as potential substrates two techniques: (a) vitro phosphorylation lysate recombinant active followed separation...
Endogenous cardiotonic glycosides bind to the inhibitory binding site of plasma membrane sodium pump (Na + /K -ATPase). Plasma levels endogenous increase in several disease states, such as essential hypertension and uremia. Low concentrations ouabain, which do not inhibit Na -ATPase, induce cell proliferation. The mechanisms ouabain-mediated response remain unclear. Recently, we demonstrated that opossum kidney (OK) proximal tubular cells, low ouabain proliferation through phosphorylation...
Abstract FcγRs mediate immune complex-induced tissue injury. The hypothesis that FcγRIIa and FcγRIIIb control neutrophil responses by activating mitogen-activated protein kinases was examined. Homotypic heterotypic cross-linking of and/or resulted in a rapid, transient increase ERK p38 activity, with maximal stimulation between 1 3 min. stimulated distinct patterns failed to stimulate synergistic activation either or activity. Both required nonreceptor tyrosine kinase phosphatidylinositol...