S-glutathionylation, friend or foe in cardiovascular health and disease.

Glutathione is a low molecular weight thiol that is present at high levels in the cell. The high levels of glutathione in the cell make it one of the most abundant antioxidants contributing to cellular redox homeostasis. As a general rule, throughout cardiovascular disease and progression there is an imbalance in redox homeostasis characterized by reactive oxygen species overproduction and glutathione underproduction. As research into these imbalances continues, glutathione concentrations are increasingly being observed to drive various physiological and pathological signaling responses. Interestingly in addition to acting directly as an antioxidant, glutathione is capable of post translational modifications (S-glutathionylation) of proteins through both chemical interactions and enzyme mediated events. This review will discuss both the chemical and enzyme-based S-glutathionylation of proteins involved in cardiovascular pathologies and angiogenesis.

Hydrogen sulfide: Therapeutic or injurious in ischemic stroke?

Hydrogen sulfide (H2S) has been identified as a vasodilatory, neuromodulatory, and anti-inflammatory gasotransmitter with antioxidant properties. Studies focused in cardiac tissue suggest H2S functions as a protective agent; however in the central nervous system (CNS) the effects of H2S during states of stress or injury, such as stroke, remain controversial. Currently, the application of H2S donors and modulators in stroke depends on the type of H2S donor and the timing of the therapy.

Molecular mimicry in inducing DNA damage between HIV-1 Vpr and the anticancer agent, cisplatin.

The human immunodeficiency virus type 1 (HIV-1) viral protein R (vpr) gene is an evolutionarily conserved gene among the primate lentiviruses. Several functions are attributed to Vpr including the ability to cause cell death, cell cycle arrest, apoptosis and DNA damage. The Vpr domain responsible for DNA damage as well as the mechanism(s) through which Vpr induces this damage is unknown. Using site-directed mutagenesis, we identified the helical domain II within Vpr (aa 37-50) as the region responsible for causing DNA damage. Interestingly, Vpr Delta(37-50) failed to cause cell cycle arrest or apoptosis, to induce Ku70 or Ku80 and to suppress tumor growth, but maintained its capability to activate the HIV-1 LTR, to localize to the nucleus and to promote nonhomologous end-joining. In addition, our cytogenetic data indicated that helical domain II induced chromosomal aberrations, which mimicked those induced by cisplatin, an anticancer agent. This novel molecular mimicry function of Vpr might lead to its potential therapeutic use as a tumor suppressor.