The role of endogenous H2S formation in reversible remodeling of lung tissue during hibernation in the Syrian hamster

During hibernation, small mammals alternate between periods of metabolic suppression and low body temperature ('torpor') and periods of full metabolic recovery with euthermic temperatures ('arousal'). Previously, we demonstrated marked structural remodeling of the lung during torpor, which is rapidly reversed during arousal. We also found that cooling of hamster cells increased endogenous production of H2S through the enzyme cystathionine-beta-synthase (CBS). H2S suppresses the immune response and increases deposition of collagen. Therefore, we examined inflammatory markers and matrix metalloproteinase (MMP) activity in relation to CBS expression and H2S levels in lungs of euthermic and hibernating Syrian hamsters. Lung remodeling during torpor was confirmed by a strong increase in both collagenous and non-collagenous hydroxyproline content. The number of leukocytes in lung was unchanged in any phase of hibernation, while adhesion molecules VCAM-1 and ICAM-1, and the inflammatory marker NF-kappa B (P65) were modestly upregulated in torpor. Gelatinase activity was decreased in lungs from torpid animals, indicating inhibition of the Zn2+-dependent MMP-2 and MMP-9. Moreover, expression of CBS and tissue levels of H2S were increased in torpor. All changes normalized during arousal. Inhibition of gelatinase activity in torpor is likely caused by quenching of Zn2+ by the sulphide ion of H2S. In accord, inhibition of CBS normalized gelatinase activity in torpid animals. Conversely, NaHS decreased the gelatinase activity of euthermic animals, which was attenuated by excess Zn2+. Similar results were obtained on the activity of the Zn2+-dependent angiotensin converting enzyme. Our data indicate that increased production of H2S through CBS in hamster lungs during torpor contributes to remodeling by inhibition of gelatinase activity and possibly by suppression of the inflammatory response. Although administration of H2S is known to induce metabolic suppression in nonhibernating mammals ('suspended animation'), this is the first report implying endogenous H2S production in natural hibernation.