Minocycline treatment suppresses juvenile development and growth by attenuating insulin/TOR signaling in Drosophila animal model.
Minocycline is a broad spectrum, semi-synthetic tetracycline analog that is used to treat bacterial infection. Recently, this drug has been receiving increasing attention for its non-antibiotic properties, including anti-inflammatory, tumor suppressive, and neuroprotective effects. Drosophila is a useful model organism for studying human metabolism and disease. In this study, we investigated the effects of minocycline on juvenile development and growth in Drosophila. Feeding minocycline to Drosophila larvae suppresses larval body growth and delays the timing of pupation in a dose-dependent manner. We found that the drug treatment decreased the activated form of Akt and S6K in peripheral tissues, which suggested that the insulin/target of rapamycin (TOR) signaling had been attenuated. Specifically enhancing TOR activity in the prothoracic gland (PG), the ecdysone-generating organ, attenuated the drug-induced developmental delay, which is consistent with the critical role of PG's TOR signaling in determining pupation time. Our results reveal previously unrecognized effects of minocycline and offer a new potential therapeutic opportunity for various pathological conditions associated with insulin/TOR signaling.
Department of Life Science, Chung-Ang University, Seoul 156-756, Korea.
Hyun Myoung
HM
Yun
Department of Life Science, Chung-Ang University, Seoul 156-756, Korea.
Sujin
S
Noh
Department of Life Science, Chung-Ang University, Seoul 156-756, Korea.
Seogang
S
Hyun
D000825:Animal Structures / Q000187:drug effects; D000818:Animals; D049628:Body Size / Q000187:drug effects; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000033:anatomy & histology / Q000187:drug effects / Q000254:growth & development* / Q000378:metabolism*; D004440:Ecdysone / Q000378:metabolism; D005247:Feeding Behavior; D007328:Insulin / Q000378:metabolism*; D007814:Larva / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D008911:Minocycline / Q000008:administration & dosage / Q000494:pharmacology*; D023421:Models, Animal; D011679:Pupa / Q000187:drug effects / Q000254:growth & development; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
D029721:Drosophila Proteins; D007328:Insulin; D004440:Ecdysone; C416303:target of rapamycin protein, Drosophila; D058570:TOR Serine-Threonine Kinases; D008911:Minocycline