Previously, we demonstrated the expression of apelin and G-protein-coupled receptor APJ in human placenta cell lines as well as its direct action on placenta cell proliferation and endocrinology. The objective of this study was to examine the effect of apelin on placenta apoptosis in BeWo cells and villous explants from the human third trimester of pregnancy. The BeWo cells and villous explants were incubated with apelin (2 and 20 ng/mL) alone or with staurosporine for 24 to 72 h. First, we analysed the dose- and time-dependent effect of apelin on the expression of apoptotic factors on the mRNA level by real-time PCR and on the protein level using Western blot. Next, we checked caspase 3 and 7 activity by Caspase-Glo 3/7, DNA fragmentation by the Cell Death Detection ELISA kit and oxygen consumption by the MitoXpress-Xtra Oxygen Consumption assay. We found that apelin increased the expression of pro-survival and decreased proapoptotic factors on mRNA and protein levels in both BeWo cells and villous explants. Additionally, apelin inhibited caspase 3 and 7 activity and DNA fragmentation in staurosporine-induced apoptosis as also attenuated oxidative stress by increasing extracellular oxygen consumption. The antiapoptotic effect of apelin in BeWo cells was mediated by the APJ receptor and mitogen-activated protein kinase (ERK1/2/MAP3/1) and protein kinase B (AKT). The obtained results showed the antiapoptotic effect of apelin on trophoblast cells, suggesting its participation in the development of the placenta.

Hydrogen sulfide (H2S) has been known for years as a poisoning gas and until recently evoked mostly negative associations. However, the discovery of its gasotransmitter functions suggested its contribution to various physiological and pathological processes. Although H2S has been found to exert cytoprotective effects through modulation of antioxidant, anti-inflammatory, anti-apoptotic, and pro-angiogenic responses in a variety of conditions, its role in the pathophysiology of skeletal muscles has not been broadly elucidated so far. The classical example of muscle-related disorders is Duchenne muscular dystrophy (DMD), the most common and severe type of muscular dystrophy. Mutations in the DMD gene that encodes dystrophin, a cytoskeletal protein that protects muscle fibers from contraction-induced damage, lead to prominent dysfunctions in the structure and functions of the skeletal muscle. However, the main cause of death is associated with cardiorespiratory failure, and DMD remains an incurable disease. Taking into account a wide range of physiological functions of H2S and recent literature data on its possible protective role in DMD, we focused on the description of the ‘old’ and ‘new’ functions of H2S, especially in muscle pathophysiology. Although the number of studies showing its essential regulatory action in dystrophic muscles is still limited, we propose that H2S-based therapy has the potential to attenuate the progression of DMD and other muscle-related disorders.

Dystrofia mięśniowa Duchenne’a (DMD) to choroba genetyczna sprzężona z chromosomem X, dotykająca w przybliżeniu 1 na 5000 urodzonych chłopców. Jest spowodowana mutacjami w genie DMD kodującym dystrofinę, która odpowiada za stabilność mechaniczną mięśni podczas skurczu. Jej brak prowadzi do postępującego osłabienia mięśni i przedwczesnej śmierci chorych w wyniku niewydolności sercowo-oddechowej. W ostatnich latach opracowano wiele eksperymentalnych terapii, których celem jest przywrócenie funkcjonalnej dystrofiny lub przeciwdziałanie procesom przyczyniającym się do postępu choroby, takim jak zapalenie czy zwłóknienie. Pomimo tego DMD wciąż pozostaje chorobą nieuleczalną, a glikokortykoidy, wykazujące wiele działań niepożądanych, nadal stanowią „złoty standard” leczenia. Aktualne jest zatem opracowywanie innowacyjnych możliwości terapeutycznych, które przynajmniej złagodzą objawy DMD. Wśród nich na uwagę zasługuje celowanie w określone mikroRNA (miR), np. miR-378a, przywrócenie prawidłowej angiogenezy oraz wykorzystanie cytoprotekcyjnych czynników takich jak oksygenaza hemowa-1 (HO-1) czy siarkowodór (H2S). W niniejszej pracy omówiono zarówno patologię choroby jak i wspomniane, nowe możliwości terapeutyczne w DMD.