Modulation of endogenous H2S production. Its role in hibernation and pharmacological cell protection

PhD ceremony: Ms. F. Talaei, 16.15 uur, Aula Academiegebouw, Broerstraat 5, Groningen

Dissertation: Modulation of endogenous H2S production. Its role in hibernation and pharmacological cell protection

Promotor(s): prof. R.H. Henning, prof. M. Schmidt

Faculty: Medical Sciences

Studying the protective mechanism(s) that small mammals, such as the hamster, employ during hibernation may disclose new strategies to limit cellular damage. We focused on the mechanism that constituted of release and re-absorption of serotonin, leading to the production of H2S via the enzyme cystathionine beta synthase (CBS). Increasing the CBS activity, both through pharmacological manipulation and the introduction of appropriate genes related to serotonin metabolism, was demonstrated to attenuate hypothermic damage in cold preserved cells and tissues of non-hibernators.

The CBS/H2S mechanism is also employed during natural hibernation. Hamster lung showed extensive remodeling during cold phases of hibernation, which was rapidly reversed during euthermic periods. Remodeling of lung corresponded with an increase in tissue CBS and H2S, promoting deposition of extracellular matrix. Activation of CBS during hibernation may also provide protection against cellular damage or limit immune activation.