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Inhibition of a calcium-dependent cysteine protease by doxycycline

Domenii publicaţii > Ştiinţe medicale + Tipuri publicaţii > Articol în revistã ştiinţificã

Autori: Nicolescu A.C., Mircioiu C

Editorial: Farmacia, 58(2), p.136-44, 2010.

Rezumat:

The activation of calcium-dependent cysteine proteases (calpains) due to an uncontrolled increase in the cellular calcium influx can lead to aberrant degradation of cellular proteins and cell death. The inhibitory effect of doxycycline on other proteases, but not calpains, has been reported. We discovered that doxycycline significantly inhibits murine calpain 2 at concentrations ≥ 30 μM. An increase in the calcium ion concentration did not affect this inhibitory effect, suggesting that doxycycline does not act by simply chelating the calcium ions. The analysis of the amino acid sequences of murine calpain 2 and human calpains 1 and 2 suggests that doxycycline is likely to have similar effects on human calpains. These results extend the non-antimicrobial activity of doxycycline to a different family of proteases, and could be used to design compounds potentially useful for modulating the activity of calpains.

Cuvinte cheie: cysteine proteases, doxycycline, enzyme inhibition

URL: http://www.revistafarmacia.ro/20102/issue22010art03.pdf