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HA Production (ha + production)

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Life Sciences	40%

Selected Abstracts

Signal pathways regulating hyaluronan secretion into static and cycled synovial joints of rabbits

THE JOURNAL OF PHYSIOLOGY, Issue 17 2009
K. R. Ingram
Joint lubrication, synovial fluid conservation and many pathophysiological processes depend on hyaluronan (HA). Intra-articular HA injection and exercise, which stimulates articular HA production, ameliorate osteoarthritis. We therefore investigated the pathways regulating movement-stimulated articular HA secretion rate () in vivo. Endogenous HA was removed from the knee joint cavity of anaesthetised rabbits by washout. Joints were then cycled passively or remained static for 5 h, with/without intra-articular agonist/inhibitor, after which newly secreted HA was harvested for analysis. Movement almost doubled . Similar or larger increases were elicited in static joints by the intra-articular Ca2+ ionophore ionomycin, prostaglandin E2, cAMP-raising agents, serine/threonine phosphatase inhibitor and activation of protein kinase C (PKC). PKC-stimulated secretion was inhibited by the PKC inhibitor bisindolylmaleimide I and inhibitors of the downstream kinases MEK-ERK (U0126, PD98059). These agents inhibited movement-stimulated secretion of HA (MSHA) only when the parallel p38 kinase path was simultaneously inhibited by SB203580 (ineffective alone). The phospholipase C inhibitor U73122 almost fully blocked MSHA (P= 0.001, n= 10), without affecting static . The ENaC channel blocker amiloride inhibited MSHA, whereas other inhibitors of stretch-activated channels (Gd3+, ruthenium red, SKF96365) did not. It is proposed that MSHA may be mediated by PLC activation, leading to activation of parallel PKC,MEK,ERK and p38 kinase pathways. [source]

Chondroitin sulfate increases hyaluronan production by human synoviocytes through differential regulation of hyaluronan synthases: Role of p38 and Akt

ARTHRITIS & RHEUMATISM, Issue 3 2009
Maha David-Raoudi
Objective To uncover the mechanism by which chondroitin sulfate (CS) enhances hyaluronan (HA) production by human osteoarthritic (OA) fibroblast-like synoviocytes (FLS). Methods The production of HA was investigated by exposing human OA FLS to CS in the presence or absence of interleukin-1, (IL-1,). HA levels were determined by enzyme-linked immunosorbent assay, and levels of messenger RNA (mRNA) for HA synthase 1 (HAS-1), HAS-2, and HAS-3 were determined by real-time polymerase chain reaction analysis. The effect of CS and IL-1, on signaling pathways was assessed by Western blotting. Specific inhibitors were used to determine their effects on both HA production and HAS expression. The molecular size of HA was analyzed by high-pressure liquid chromatography. Results CS increased HA production by FLS through up-regulation of the expression of HAS1 and HAS2. This was associated with activation of ERK-1/2, p38, and Akt, although to a lesser extent. Both p38 and Akt were involved in CS-induced HA accumulation. IL-1, increased HA production and levels of mRNA for HAS1, HAS2, and HAS3. CS enhanced the IL-1,,induced level of HAS2 mRNA and reduced the level of HAS3 mRNA. IL-1,,induced activation of p38 and JNK was slightly decreased by CS, whereas that of ERK-1/2 and Akt was enhanced. More high molecular weight HA was found in CS plus IL-1,,treated FLS than in FLS treated with IL-1, alone. Conclusion CS stimulates the synthesis of high molecular weight HA in OA FLS through up-regulation of HAS1 and HAS2. It reduces the IL-1,,enhanced transcription of HAS3 and increases the production of HA of large molecular sizes. These effects may be beneficial for maintaining viscosity and antiinflammatory properties in the joint. [source]

Sensitivity to Hydrogen Peroxide of Growth and Hyaluronic Acid Production by Streptococcus zooepidemicus ATCC 39920

ASIA-PACIFIC JOURNAL OF CHEMICAL ENGINEERING, Issue 5-6 2005
M.D. Mashitah
Abstract The sensitivity to hydrogen peroxide (H2O2) of growth and hyaluronic acid (HA) production by Streptococcus zooepidemicus ATCC 39920 was studied under various conditions. In sheep blood agar-plates, no detectable zone was observed even when the concentration of H2O2 was increased to 0.15 mM. With brain heart infusion-agar and chemically defined medium-agar plates, a profound zone was detected at 0.015 mM concentration of H2O2. To determine the minimal inhibitory concentration (MIC) of the strain in culture broth, various concentrations of H2O2 (0-200 mM) were maintained in the medium prior to fermentation. The result showed that for higher concentrations of H2O2 in the medium, the greater was the inhibition. Streptococcus is catalase-negative and known to produce H2O2 which may affect growth, HA production and glucose utilization. In order to determine at which growth phase H2O2 had the maximum inhibitory activity, a batch fermentation of S. zooepidemicus was conducted in shake flask culture. It was found that H2O2 production took place during the growth phase, and HA production started after the growth had reach late exponential phase when H2O2 in the culture media was depleted. This indicates that H2O2 produced by the cells did not affect cell growth but influenced HA production. [source]

Enhanced Hyaluronic Acid Production in Bacillussubtilis by Coexpressing Bacterial Hemoglobin

BIOTECHNOLOGY PROGRESS, Issue 5 2007
Liang-Jung Chien
Bacillus subtilis strains that can produce hyaluronic acid (HA) were constructed by integrating the HA synthase gene (hasA) and the UDP-glucose dehydrogenase gene of group C Streptococcus (hasB) or of B. subtilis itself (tauD) into the amyE locus of the B. subtilis chromosome. All of the inserted genes were under the control of a strong constitutive vegII promoter of B. subtilis. Although HA production could be achieved by expressing hasA alone, coexpressing hasB or tauD with hasA could enhance HA production at least 2-fold. To replenish the energy consumed for HA biosynthesis, Vitreoscilla hemoglobin (VHb) was coexpressed with the HA-expressing genes. With the expression of VHb, not only the cell concentration was enhanced 25%, but also HA production was further increased by 100%. About 1.8 g/L of HA was obtained by the recombinant strain B.subtilis carrying VHb, hasA, and tauD genes in the expression cassette after 30 h cultivation. [source]