- Heat shock proteins research
- Connexins and lens biology
- Enzyme Structure and Function
- Exercise and Physiological Responses
- Meat and Animal Product Quality
- Endoplasmic Reticulum Stress and Disease
- Renal Diseases and Glomerulopathies
- RNA and protein synthesis mechanisms
- Protein Structure and Dynamics
- Physiological and biochemical adaptations
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Viral Infectious Diseases and Gene Expression in Insects
- thermodynamics and calorimetric analyses
- Bee Products Chemical Analysis
- Spaceflight effects on biology
- Healthcare and Venom Research
- Thermoregulation and physiological responses
- Insect and Pesticide Research
- Toxin Mechanisms and Immunotoxins
- Trace Elements in Health
- Hereditary Neurological Disorders
- RNA modifications and cancer
- Ion Transport and Channel Regulation
- Photosynthetic Processes and Mechanisms
- Cancer, Hypoxia, and Metabolism
Temple University
2022
Nationwide Children's Hospital
2010-2021
The Ohio State University
2010-2021
University of Michigan
1999-2018
Humboldt-Universität zu Berlin
2007
Max Delbrück Center
1992-2001
University of Wisconsin–Madison
1999
University of Lübeck
1999
Charité - Universitätsmedizin Berlin
1997
Philips (Germany)
1997
Characteristic features of mammalian small heat shock proteins are their rapid phosphorylation in response to stress and mitogenic signals ability form multimeric particles 200-700 kDa large aggregates up 5000 kDa. Recently, a chaperoning function an actin polymerization-inhibiting activity were demonstrated for the recombinant murine turkey protein, respectively. In this paper, we demonstrate that protein HSP25 is dependent on degree its structural organization. Non-phosphorylated...
Native phosphorylated mouse small heat shock protein hsp25 from Ehrlich ascites tumor cells was isolated and the in vivo phosphorylation sites of were determined. Furthermore, native by endogenous kinase(s) a cell-free system as well recombinant vitro kinase C catalytic subunit cAMP-dependent kinase. The two major determined Ser-15 Ser-86. There are no differences C, unknown intracellular kinase(s). serine residues identified exist all known mammalian stress proteins located conserved...
Background In the heart, there are high constitutive levels of two related small heat shock proteins, HSP25 and αB-crystallin. To gain insight into their functional role, we have analyzed abundance location both proteins in rat human hearts at different stages development diseased state. Methods Results Immunoblotting analysis ventricular tissue fetal, neonatal, adult reveals level to decline strongly during development, whereas αB-crystallin remains nearly constant. parallel, portion...
Mammalian small heat shock proteins (sHSP) are abundant in muscles and implicated both muscle function myopathies. Recently a new sHSP, HSP22 (HSPB8, H11), was identified the human heart by its interaction with HSP27 (HSPB1). Using phylogenetic analysis we show that is true member of sHSP superfamily. sHSPs interact each other form homo- hetero-oligomeric complexes. The these complexes poorly understood. gel filtration HPLC, yeast two-hybrid method, immunoprecipitation, cross-linking,...
The growth‐related 25‐kDa protein (p25) of Ehrlich ascites tumor (EAT) has been characterized by molecular cloning and sequencing cDNA clones detected hybridization with oligonucleotide probes synthesized according to the amino acid sequence a tryptic peptide p25. Detection p25 mRNA in EAT exponential growth phase stationary using cDNA‐derived RNA demonstrated that abundance is also growth‐related. High‐level expression Escherichia coli established oligonucleotide‐directed mutagenesis...
The interaction of small heat shock proteins (sHSPs) with the actin cytoskeleton has been described and some members this family, e.g. chicken murine HSP25 (HSP27), inhibit polymerization in vitro . To analyse molecular basis interaction, we synthesized a set overlapping peptides covering complete sequence tested effect these on by fluorescence spectroscopy electron microscopy. Two comprising sequences W43 to R57 (peptide 6) I92 N106 11) were found be potent inhibitors polymerization....
AlphaB-crystallin and heat shock protein (hsp) 25 are structurally functionally related small stress proteins induced by a variety of insults, including ischemia. Cytoprotection these two hsp is thought to result from molecular chaperoning and/or cytoskeletal stabilization. Because renal ischemia characterized disruption the tubular cell actin cytoskeleton, this study was conducted determine localization quantify expression phosphorylation both in cortex, isolated glomeruli, outer medulla,...
Two mutations (K141E, K141N) in the small heat shock protein (sHSP) HSP22 (HSPB8) are associated with inherited peripheral motor neuron disorders distal hereditary neuropathy type II and axonal Charcot-Marie-Tooth disease 2L. is known to form homodimers, heterodimers other sHSPs, larger oligomers. In an effort elucidate cellular basis for these diseases, we have determined ability of mutant interact itself, wild-type HSP22, sHSPs that abundant neurons. Using yeast two-hybrid method,...
Glucocorticoids (GC) are the primary therapy for idiopathic nephrotic syndrome (NS). Recent evidence has identified glomerular podocytes as a potential site of GC action in this disease. The objectives study were to determine presence key components glucocorticoid receptor (GR) complex and functionality signaling pathway explore opportunities manipulation responsiveness. Here, we show that cultured murine express GR complex, including GR, heat shock protein 90, immunophilins FKBP51 FKBP52....
We investigated how heat shock protein 27 (HSP27) and its phosphorylation are involved in the action of cholecystokinin (CCK) on actin cytoskeleton by genetic manipulation Chinese hamster ovary (CHO) cells stably transfected with CCK-A receptor. In these cells, as rat acini, CCK activated p38 mitogen-activated (MAP) kinase increased HSP27. This effect could be blocked MAP inhibitor SB-203580. Examination confocal microscopy stained rhodamine phalloidin showed that dose-dependently induced...
Three mutations (R120G, Q151X, and 464delCT) in the small heat shock protein alphaB-crystallin cause inherited myofibrillar myopathy. In an effort to elucidate molecular basis for associated myopathy, we have determined following these mutant proteins: (i) formation of aggregates transfected cells; (ii) partition into different subcellular fractions; (iii) phosphorylation status; (iv) ability interact with themselves, wild-typealphaB-crystallin, other proteins that are abundant muscles. We...
Glucocorticoids are the primary therapy for nephrotic syndrome (NS), but have serious side effects and ineffective in ~20-50% of patients. Thiazolidinediones recently been suggested to be renoprotective, modulate podocyte glucocorticoid-mediated nuclear receptor signaling. We hypothesized that thiazolidinediones could enhance glucocorticoid efficacy NS. found puromycin aminonucleoside-induced proteinuria rats was significantly reduced by both high-dose glucocorticoids (79%) pioglitazone...
The dephosphorylation of the mouse small heat shock protein hsp25 within an extract obtained from Ehrlich ascites tumor cells is inhibited by calcium chelator EGTA and at concentrations microcystin-LR which are characteristic for inhibition calcium/calmodulin-dependent (2B type) phosphatases. Furthermore, in cell-free system derived could be increased specifically addition phosphatase calcineurin. Dephosphorylation also vitro containing phosphorylated recombinant hsp25, 1 mM Ca2+,...
The environmental pollutant cadmium affects human health, with the kidney being a primary target. In addition to proximal tubules, glomeruli and their contractile mesangial cells have also been identified as targets of nephrotoxicity. Glomerular contraction is thought contribute reduced glomerular filtration, characteristic Because p38 MAPK/HSP25 signaling has implicated in smooth muscle contraction, we examined its role cadmium-induced cells. We report that exposure resulted 1) cell 2)...
A number of missense mutations in the two related small heat shock proteins HspB8 (Hsp22) and HspB1 (Hsp27) have been associated with inherited motor neuron diseases (MND) distal hereditary neuropathy Charcot-Marie-Tooth disease. interact each other, suggesting that these etiologic factors may act through a common biochemical mechanism. However, their role biology MND is not understood. In yeast two-hybrid screen, we identified DEAD box protein Ddx20 (gemin3, DP103) as interacting partner...