Tat-ATOX1 inhibits inflammatory responses via regulation of MAPK and NF-κB pathways.

Abstract

Antioxidant 1 (ATOX1) protein has been reported to exhibit various protective functions, including antioxidant and chaperone. However, the effects of ATOX1 on the inflammatory response has not been fully elucidated. Thus, we prepared cell permeable Tat-ATOX1 and studied the effects on lipopolysaccharide (LPS)- and 12-O-tetradecanoyl phorbol-13- acetate (TPA)-induced inflammation. Experimental results showed that transduced Tat-ATOX1 protein significantly suppressed LPS-induced intracellular reactive oxygen species (ROS). Also, Tat-ATOX1 protein markedly inhibited LPS- and TPA-induced inflammatory responses by decreasing cyclooxygenase- 2 (COX-2) and inducible nitric oxide synthase (iNOS) and further inhibited phosphorylation of mitogen activated protein kinases (MAPKs; JNK, ERK and p38) and the nuclear factor-kappaB (NF-κB) signaling pathway. These results indicate that the Tat-ATOX1 protein has a pivotal role in inflammation via inhibition of inflammatory responses, suggesting Tat-ATOX1 protein may offer a therapeutic strategy for inflammation. [BMB Reports 2018; 51(12): 654-659].

• Authors: Dae Won Kim, Min Jea Shin, Yeon Joo Choi, Hyun Jung Kwon, Sung Ho Lee, Sunghou Lee, Jinseu Park, Kyu Hyung Han, Won Sik Eum, Soo Young Choi
• Journal: BMB reports (BMB Rep) Vol. 51 Issue 12 Pg. 654-659 (Dec 2018) ISSN: 1976-670X [Electronic] Korea (South)
• PMID: 30545441 (Publication Type: Journal Article)

Chemical References

• Atox1 protein, mouse
• Cation Transport Proteins
• Copper Transport Proteins
• Lipopolysaccharides
• Molecular Chaperones
• NF-kappa B
• Reactive Oxygen Species
• Recombinant Fusion Proteins
• Nitric Oxide Synthase Type II
• Cyclooxygenase 2
• Mitogen-Activated Protein Kinases
• Tetradecanoylphorbol Acetate

Topics

• Animals
• Cation Transport Proteins (genetics, metabolism)
• Copper Transport Proteins
• Cyclooxygenase 2 (metabolism)
• Disease Models, Animal
• Down-Regulation (drug effects)
• Edema (chemically induced, pathology)
• Lipopolysaccharides (pharmacology)
• Male
• Mice
• Mice, Inbred ICR
• Mitogen-Activated Protein Kinases (metabolism)
• Molecular Chaperones (genetics, metabolism)
• NF-kappa B (metabolism)
• Nitric Oxide Synthase Type II (metabolism)
• RAW 264.7 Cells
• Reactive Oxygen Species (metabolism)
• Recombinant Fusion Proteins (genetics, metabolism)
• Signal Transduction (drug effects)
• Tetradecanoylphorbol Acetate (toxicity)