1.
Bacterial Defense Systems against the Neutrophilic Oxidant Hypochlorous Acid.
Sultana, S, Foti, A, Dahl, JU
Infection and immunity. 2020;(7)
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Abstract
Neutrophils kill invading microbes and therefore represent the first line of defense of the innate immune response. Activated neutrophils assemble NADPH oxidase to convert substantial amounts of molecular oxygen into superoxide, which, after dismutation into peroxide, serves as the substrate for the generation of the potent antimicrobial hypochlorous acid (HOCl) in the phagosomal space. In this minireview, we explore the most recent insights into physiological consequences of HOCl stress. Not surprisingly, Gram-negative bacteria have evolved diverse posttranslational defense mechanisms to protect their proteins, the main targets of HOCl, from HOCl-mediated damage. We discuss the idea that oxidation of conserved cysteine residues and partial unfolding of its structure convert the heat shock protein Hsp33 into a highly active chaperone holdase that binds unfolded proteins and prevents their aggregation. We examine two novel members of the Escherichia coli chaperone holdase family, RidA and CnoX, whose thiol-independent activation mechanism differs from that of Hsp33 and requires N-chlorination of positively charged amino acids during HOCl exposure. Furthermore, we summarize the latest findings with respect to another bacterial defense strategy employed in response to HOCl stress, which involves the accumulation of the universally conserved biopolymer inorganic polyphosphate. We then discuss sophisticated adaptive strategies that bacteria have developed to enhance their survival during HOCl stress. Understanding bacterial defense and survival strategies against one of the most powerful neutrophilic oxidants may provide novel insights into treatment options that potentially compromise the ability of pathogens to resist HOCl stress and therefore may increase the efficacy of the innate immune response.
2.
Curcuminoids modulate pro-oxidant-antioxidant balance but not the immune response to heat shock protein 27 and oxidized LDL in obese individuals.
Sahebkar, A, Mohammadi, A, Atabati, A, Rahiman, S, Tavallaie, S, Iranshahi, M, Akhlaghi, S, Ferns, GA, Ghayour-Mobarhan, M
Phytotherapy research : PTR. 2013;(12):1883-8
Abstract
Curcuminoids have potentially important functional qualities including anti-inflammatory and antioxidant properties. In this randomized double-blind placebo-controlled cross-over trial, the effects of a curcuminoid supplement on serum pro-oxidant-antioxidant balance (PAB) and antibody titres to Hsp27 (anti-Hsp27) and oxLDL (anti-oxLDL) were investigated. Thirty obese individuals were randomized to receive either curcuminoids (1 g/day) or placebo for a period of 30 days. After a wash-out period of 2 weeks, subjects were crossed over to the alternate regimen for another 30 days. Serum PAB along with anti-Hsp27 and anti-oxLDL titres was measured at the beginning and at the end of each study period. There was no significant carry-over effect for any of the assessed parameters. Curcuminoid supplementation was associated with a significant decrease in PAB (pā=ā0.044). However, no significant change was observed in serum concentrations of anti-Hsp27 or anti-oxLDL (pā>ā0.05). These findings suggest that oral curcuminoids supplementation (1g/day) is effective in reducing oxidative stress burden, though this needs to be validated in larger study populations.
3.
Hydrogen peroxide activation of endothelial cell-associated MMPs during VCAM-1-dependent leukocyte migration.
Cook-Mills, JM
Cellular and molecular biology (Noisy-le-Grand, France). 2006;(4):8-16
Abstract
Leukocyte migration from the blood into tissues is vital for immune surveillance and inflammation. Specificity for the site of leukocyte migration is determined by the combination and concentration of adhesion molecules, cytokines and chemokines in the microenvironment. Leukocytes bound at sites of extravasation migrate within minutes. We have focused on the function of the adhesion molecule VCAM-1 and have reported an active function for the endothelium during VCAM- 1-dependent leukocyte migration. VCAM-1 activates endothelial cell NADPH oxidase followed by the generation of 1 microM H2O2. This stimulates endothelial cell-associated matrix metalloproteinase (MMP) activity in minutes, consistent with the time for lymphocyte migration. The endothelial cell NADPH oxidase and endothelial cell MMP activities are required for VCAM-1-dependent lymphocyte migration as determined by scavenging of ROS, by pharmacologic or antisense inhibition of NADPH oxidase and by pharmacologic inhibition of endothelial cell MMPs. Furthermore, antioxidants block VCAM-1 activation of MMPs. In vivo, administration of the antioxidant bilirubin blocks VCAM-1-dependent leukocyte migration into the lung in experimental asthma. In summary, endothelial cells are not simply a scaffold for leukocyte adhesion. Instead, endothelial cells have an active function during VCAM-1-dependent leukocyte transendothelial migration.