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Inhibition of the mammalian Target of Rapamycin (mTOR) does not alter nitric oxide or superoxide levels in human skin
Author(s) -
Zhao Joan L,
Roman Linda J,
Wu Yubo,
Johnson John M,
Kellogg Dean L
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.lb699
Subject(s) - superoxide , nitric oxide , chemistry , microdialysis , pharmacology , human skin , extracellular , biochemistry , medicine , biology , enzyme , organic chemistry , genetics
In laboratory animals, mTOR inhibition for 7 days causes significant reductions in nitric oxide (NO) levels with concomitant increases in superoxide production. We hypothesized mTOR inhibition by rapamycin would effect similar changes in humans. 8% rapamycin ointment (RAPA) was applied twice daily for 7 days to an 8×8 cm area of skin on the abdomen while a similar second site was treated with the ointment vehicle only. 5 middleaged persons participated. Selective amperometric electrodes placed intradermally within both skin areas monitored NO levels. Superoxide levels were monitored by perfusing the intradermal microdialysis probes at both skin areas with a solution of saline containing oxidized ferricytochrome c and analyzing for reduced cytochrome c in the collected perfusates. Superoxide in the cutaneous interstitial space diffuses across the probe membrane, forming reduced ferrocytochrome c and altering the spectrophotometric absorbance. Results NO levels at RAPA treated sites averaged 811±72nM and 526±56nM at vehicle treated sites. These values did not differ between RAPA and vehicle treated sites (p>;0.50 between site). Superoxide levels at RAPA sites averaged 11.73±2.17μM and 11.29±1.90μM at vehicle treated sites. These levels did not differ between sites (p>;0.40). We conclude that chronic RAPA treatment does not alter NO or superoxide levels in human skin. (supported by NIH Grant AG041365)