Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.3.1.108 (TAT)
 2,389 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neuroglobin (Ngb) is a heme protein that is primarily localised in the retina and the brain. Its physiological role is largely unknown. It has been reported that its overexpression protects neurons from hypoxia in vitro and in vivo, suggesting that the rapid modulation of the Ngb level in the nerve cells may be a promising stroke treatment strategy. In this study, we used a novel approach to overexpress Ngb and evaluate its ability to promote neuronal survival under hypoxic conditions. We constructed a human recombinant Ngb fused to the cell penetrating peptide (CPP) derived from HIV-1 TAT. Purified recombinant TAT-Ngb was able to efficiently transduce CHO and SHSY5Y cells, when added to the culture media. The potential neuroprotective action of Ngb was then examined by using an in vitro model of ischemia. The two neuronal cell lines RGC-5 and SH-SY5Y were subjected to oxygen glucose deprivation (OGD) after pre-treatment with TAT-Ngb. In both cell types, however, the treatment with the TAT-Ngb fusion protein did not show any effect on cell viability. This discrepancy to earlier reports might be due to the experimental model for oxygen glucose deprivation we employed. Alternatively, intracellular delivery of Ngb by the TAT/CPP might not have beneficial effects in the treatment of ischemic pathology.
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PMID:Intracellular delivery of Neuroglobin using HIV-1 TAT protein transduction domain fails to protect against oxygen and glucose deprivation. 1756 57

Neurological diseases have a close relationship to excessive reactive oxygen species (ROS). Neuroglobin (Ngb), an intrinsic protective factor, protected cells from hypoxic/ischemic injury. In the present, we reported a novel neuroprotective manganese porphyrin reconstituted metal protein, Mn-TAT PTD-Ngb, consisting of a HIV Tat protein transduction domain sequence (TAT PTD) attached to the N-terminal of apo-Ngb. Mn-TAT PTD-Ngb had a stronger ROS scavenging ability than that of TAT PTD-Ngb, and reduced intracellular ROS production and restored the function of the mitochondria and inhibited the mitochondria-dependent apoptosis. Besides, Mn-TAT PTD-Ngb activated the phosphoinositide-3 kinase (PI3K)/Akt signaling pathway, which up-regulated the expression of nuclear factor E2-related factor 2 (Nrf2), Heme oxygenase-1 (HO-1), superoxide dismutase (SOD), catalase (CAT). The results showed that the redox chemistry of Mn-TAT PTD-Ngb and redox regulation of multiple signaling pathways attenuated the oxidative injury.
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PMID:Mn-TAT PTD-Ngb attenuates oxidative injury by an enhanced ROS scavenging ability and the regulation of redox signaling pathway. 3188 13