Reversible Oxidative Modifications in Myoglobin and Functional Implications.

Myoglobin (Mb), an oxygen-binding heme protein highly expressed in heart and skeletal muscle, has been shown to undergo oxidative modifications on both an inter- and intramolecular level when exposed to hydrogen peroxide (HO) in vitro. Here, we show that exposure to HO increases the peroxidase activity of Mb. Reaction of Mb with HO causes covalent binding of heme to the Mb protein (Mb-X), corresponding to an increase in peroxidase activity when ascorbic acid is the reducing co-substrate.

A peroxidase mimetic protects skeletal muscle cells from peroxide challenge and stimulates insulin signaling.

Reactive oxygen species such as hydrogen peroxide have been implicated in causing metabolic dysfunction such as insulin resistance. Heme groups, either by themselves or when incorporated into proteins, have been shown to scavenge peroxide and demonstrate protective effects in various cell types. Thus, we hypothesized that a metalloporphyrin similar in structure to heme, Fe(III)tetrakis(4-benzoic acid)porphyrin (FeTBAP), would be a peroxidase mimetic that could defend cells against oxidative stress.

Myoglobin as a versatile peroxidase: Implications for a more important role for vertebrate striated muscle in antioxidant defense.

Myoglobins (Mb) are ubiquitous proteins found in striated muscle of nearly all vertebrate taxa. Although their function is most commonly associated with facilitating oxygen storage and diffusion, Mb has also been implicated in cellular antioxidant defense. The oxidized (Fe) form of Mb (metMB) can react with hydrogen peroxide (HO) to produce ferrylMb.

Nuclear envelope assembly defects link mitotic errors to chromothripsis.

Defects in the architecture or integrity of the nuclear envelope are associated with a variety of human diseases. Micronuclei, one common nuclear aberration, are an origin for chromothripsis, a catastrophic mutational process that is commonly observed in cancer. Chromothripsis occurs after micronuclei spontaneously lose nuclear envelope integrity, which generates chromosome fragmentation.

The paradoxical role of IL-10 in immunity and cancer.

Interleukin-10 (IL-10) produced by a wide-variety of cells is a highly pleiotropic cytokine. It has been implicated in the pathogenesis and/or development of autoimmune diseases and cancer, although it displays differential effects that seem to be contradictory sometimes. The ultimate role of this cytokine in disease, however, cannot be fully determined until the immunological contexts that regulate its function are further elucidated.