Researchers at Vanderbilt University have identified importin alpha 5, a member of a family of proteins that “shuttle” other proteins known as stress-responsive transcription factors into the nucleus, as a potential new target for drugs to treat inflammatory diseases.
Jozef Zienkiewicz, Ph.D., Amy Armitage and Jacek Hawiger, M.D., Ph.D., demonstrated in human cells that a peptide (protein fragment), N50, preferentially bound to importin alpha 5 by mimicking the nuclear localization sequence of NF-kappa B, a pro-inflammatory stress-responsive transcription factor.
The finding was reported in the September issue of the Journal of the American Heart Association. The Vanderbilt team previously reported that a cell-penetrating form of this peptide lowered cholesterol, triglyceride and glucose levels, and suppressed atherosclerosis and fatty liver disease in mice.
In the current study, they concluded that by preventing importin alpha 5 “shuttling” of proinflammatory activators into the nucleus, N50-containing drugs potentially could inhibit “signaling pathways evoked by metabolic, autoimmune and microbial stimuli that cause inflammatory disorders.”
The research was supported by National Institute of Health grants HL085833 and AA015752.
