Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
, 67, 195-210

Tat-glyoxalase Protein Inhibits Against Ischemic Neuronal Cell Damage and Ameliorates Ischemic Injury

Affiliations

Tat-glyoxalase Protein Inhibits Against Ischemic Neuronal Cell Damage and Ameliorates Ischemic Injury

Min Jea Shin et al. Free Radic Biol Med.

Abstract

Methylglyoxal (MG), a metabolite of glucose, is the major precursor of protein glycation and induces apoptosis. MG is associated with neurodegeneration, including oxidative stress and impaired glucose metabolism, and is efficiently metabolized to S-D-lactoylglutathione by glyoxalase (GLO). Although GLO has been implicated as being crucial in various diseases including ischemia, its detailed functions remain unclear. Therefore, we investigated the protective effect of GLO (GLO1 and GLO2) in neuronal cells and an animal ischemia model using Tat-GLO proteins. Purified Tat-GLO protein efficiently transduced into HT-22 neuronal cells and protected cells against MG- and H2O2-induced cell death, DNA fragmentation, and activation of caspase-3 and mitogen-activated protein kinase. In addition, transduced Tat-GLO protein increased D-lactate in MG- and H2O2-treated cells whereas glycation end products (AGE) and MG levels were significantly reduced in the same cells. Gerbils treated with Tat-GLO proteins displayed delayed neuronal cell death in the CA1 region of the hippocampus compared with a control. Furthermore, the combined neuroprotective effects of Tat-GLO1 and Tat-GLO2 proteins against ischemic damage were significantly higher than those of each individual protein. Those results demonstrate that transduced Tat-GLO protein protects neuronal cells by inhibiting MG- and H2O2-mediated cytotoxicity in vitro and in vivo. Therefore, we suggest that Tat-GLO proteins could be useful as a therapeutic agent for various human diseases related to oxidative stress including brain diseases.

Keywords: Glyoxalase (GLO); Ischemic damage; Methylglyoxal (MG); Oxidative stress; Protein therapy.

Similar articles

See all similar articles

Cited by 18 PubMed Central articles

See all "Cited by" articles

Publication types

MeSH terms

Feedback