Apomorphine is a potent inhibitor of ferroptosis independent of dopaminergic receptors.

Originally, apomorphine was a broad-spectrum dopamine agonist with an affinity for all subtypes of the Dopamine D1 receptor to the D5 receptor. We previously identified apomorphine as a potential therapeutic agent for mitochondrial diseases by screening a chemical library of fibroblasts from patients with mitochondrial diseases. In this study, we showed that apomorphine prevented ferroptosis in fibroblasts from various types of mitochondrial diseases as well as in normal controls. Well-known biomarkers of ferroptosis include protein markers such as prostaglandin endoperoxide synthase 2 (PTGS2), a key gene for ferroptosis-related inflammation PTGS2, lipid peroxidation, and reactive oxygen species. Our findings that apomorphine induced significant downregulation of PTSG2 and suppressed lipid peroxide to the same extent as other inhibitors of ferroptosis also indicate that apomorphine suppresses ferroptosis. To our knowledge, this is the first study to report that the anti-ferroptosis effect of apomorphine is not related to dopamine receptor agonist action and that apomorphine is a potent inhibitor of ferroptotic cell death independent of dopaminergic receptors.

Involvement of Auxin Biosynthesis and Transport in the Antheridium and Prothalli Formation in Lygodium japonicum.

The spores of Lygodium japonicum, cultured in the dark, form a filamentous structure called protonema. Earlier studies have shown that gibberellin (GA) induces protonema elongation, along with antheridium formation, on the protonema. In this study, we have performed detailed morphological analyses to investigate the roles of multiple phytohormones in antheridium formation, protonema elongation, and prothallus formation in L. japonicum. GA4 methyl ester is a potent GA that stimulates both protonema elongation and antheridium formation. We found that these effects were inhibited by simultaneous application of abscisic acid (ABA). On the other hand, IAA (indole-3-acetic acid) promoted protonema elongation but reduced antheridium formation, while these effects were partially recovered by transferring to an IAA-free medium. An auxin biosynthesis inhibitor, PPBo (4-phenoxyphenylboronic acid), and a transport inhibitor, TIBA (2,3,5-triiodobenzoic acid), both inhibited protonema elongation and antheridium formation. L. japonicum prothalli are induced from germinating spores under continuous white light. Such development was negatively affected by PPBo, which induced smaller-sized prothalli, and TIBA, which induced aberrantly shaped prothalli. The evidence suggests that the crosstalk between these plant hormones might regulate protonema elongation and antheridium formation in L. japonicum. Furthermore, the possible involvement of auxin in the prothalli development of L. japonicum is suggested.