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Alcohol metabolism's various processes create harmful compounds that contribute to cell and tissue damage. In particular, the enzyme cytochrome P450 2E1 (CYP2E1) plays a role in creating a harmful condition [...]

Substantial evidence now exists that intrinsic free-radical scavenging contributes to the receptor-independent neuroprotective effects of estrogens. This activity is inherently associated with the presence of a phenolic A-ring in the steroid. We report a previously unrecognized antioxidant cycle that maintains the 'chemical shield' raised by estrogens against the most harmful reactive oxygen species, the hydroxyl radical (*OH) produced by the Fenton reaction. In this cycle, the capture of *OH was shown to produce a nonphenolic quinol with no affinity to the estrogen receptors. This quinol is then rapidly converted back to the parent estrogen via an enzyme-catalyzed reduction by using NAD(P)H as a coenzyme (reductant) and, unlike redox cycling of catechol estrogens, without the production of reactive oxygen species. Due to this process, protection of neuronal cells against oxidative stress is also possible by quinols that essentially act as prodrugs for the active hormone. We have shown that the quinol obtained from a 17[beta]-estradiol derivative was, indeed, able to attenuate glutamate-induced oxidative stress in cultured hippocampus-derived HT-22 cells. Estrone quinol was also equipotent with its parent estrogen in reducing lesion volume in ovariectomized rats after transient middle carotid artery occlusion followed by a 24-h reperfusion. These findings may establish the foundation for a rational design of neuroprotective antioxidants focusing on steroidal quinols as unique molecular leads. hydroxyl radical | ischemia | prodrug

Integrin-mediated reorganization of cell shape leads to an altered cellular phenotype. Disruption of the actin cytoskeleton, initiated by binding of soluble antibody to [Alpha]5Β1 integrin, led to increased expression of the collagenase-1 gene in rabbit synovial fibroblasts. Activation of the guanosine triphosphate-binding protein Rac1, which was downstream of the integrin, was necessary for this process, and expression of activated Rac1 was sufficient to increase expression of collagenase-1. Rac1 activation generated reactive oxygen species that were essential for nuclear factor kappa B-dependent transcriptional regulation of interleukin-1[Alpha], which, in an autocrine manner, induced collagenase-1 gene expression. Remodeling of the extracellular matrix and consequent alterations of integrin-mediated adhesion and cytoarchitecture are central to development, wound healing, inflammation, and malignant disease. The resulting activation of Rac1 may lead to altered gene regulation and alterations in cellular morphogenesis, migration, and invasion., Modifications of cell shape are crucial for tissue morphogenesis, cell migration, and invasion. These alterations in cell morphology are thought to rely on the organization of the actin cytoskeleton and [...]

Kinetic analysis indicates that oxygen reactivity is affected by enzymes including lipoxygenase-1 without involving metal cofactors. Data show that the iron cofactor of the enzyme generates an enzyme-bound radical, which is encountered by oxygen.

Research has been conducted on flavin mononucleotide-binding LOV1 domain of the Phot1-receptor from Chlamydomonas reibhardtii. The authors have replaced LOV1 domain's photoreactive cysteine C57 by methionine, and the results have demonstrated that the photoexcitation of the C57M mutant produces metastable photoproduct which decomposes into a stable paramagnetic species with red-shift absorption.