Iron Availability Modulates the Response of Endosymbiotic Dinoflagellates to Heat Stress.

Warming and nutrient limitation are stressors known to weaken the health of microalgae. In situations of stress, access to energy reserves can minimize physiological damage. Because of its widespread requirements in biochemical processes, iron is an important trace metal, especially for photosynthetic organisms. Lowered iron availability in oceans experiencing rising temperatures may contribute to the thermal sensitivity of reef-building corals, which rely on mutualisms with dinoflagellates to survive. To test the influence of iron concentration on thermal sensitivity, the physiological responses of cultured symbiotic dinoflagellates (genus Breviolum; family Symbiodiniaceae) were evaluated when exposed to increasing temperatures (26 to 30°C) and iron concentrations ranging from replete (500 pM Fe') to limiting (50 pM Fe') under a diurnal light cycle with saturating radiance. Declines in photosynthetic efficiency at elevated temperatures indicated sensitivity to heat stress. Furthermore, five times the amount of iron was needed to reach exponential growth during heat stress (50 pM Fe' at 26-28°C vs. 250 pM Fe' at 30°C). In treatments where exponential growth was reached, Breviolum psygmophilum grew faster than B.minutum, possibly due to greater cellular contents of iron and other trace metals. The metal composition of B.psygmophilum shifted only at the highest temperature (30°C), whereas changes in B.minutum were observed at lower temperatures (28°C). The influence of iron availability in modulating each alga's response to thermal stress suggests the importance of trace metals to the health of coral-algal mutualisms. Ultimately, a greater ability to acquire scarce metals may improve the tolerance of corals to physiological stressors and contribute to the differences in performance associated with hosting one symbiont species over another.

Osteoclastogenesis Inhibitory Polyketides from the Sponge-Associated Fungus Xylaria feejeensis.

A new ten-membered macrolide (1) and a new α-pyrone derivative, (-)-annularin C (2), together with 14 known analogs (3-16) were isolated from the AcOEt extract of the fungus Xylaria feejeensis isolated from the South China Sea sponge Stylissa massa. The structures of the new compounds were elucidated by the spectroscopic analysis and by comparison with reported data. The absolute configuration was determined by the optical rotation and ECD experiments. In an in vitro test, compounds 1, 5 and 9 exhibited significant down-regulating activity of osteoclast cell differentiation at 0.5 and 1 µm. This is the first report of the fungus X. feejeensis from a marine sponge and of osteoclastogenesis inhibitory activity for the metabolites of these kinds.

Immunomodulatory Polyketides from a Phoma-like Fungus Isolated from a Soft Coral.

Fourteen new polyketides with a trans-fused decalin ring system, libertalides A-N (3-16), together with two known analogues, aspermytin A and its acetate (1, 2), were isolated from the fermentation extract of a coral-derived Libertasomyces sp. fungus. Their relative configurations were elucidated on the basis of detailed spectroscopic analysis, and the absolute configurations were determined by TDDFT-ECD and optical rotation (OR) calculations. The OR of 1 and 2 were found to have opposite signs in CH3CN and CHCl3, which was in agreement with the OR calculations producing alternating signs for the optical rotation depending on the applied conditions. Because the signs of the OR for 1 and 2 showed high solvent dependence, they may not be used alone to correlate the absolute configurations. Compound 16 displayed structural novelty characterized by an α-enol ether bridge conjugated with an aldehyde group. In in vitro immunomodulatory screening, compounds 1, 4, and 10 significantly induced the proliferation of CD3+ T cells, while compounds 2, 7, 11, and 14 significantly increased the CD4+/CD8+ ratio at 3 µM. A preliminary structure-activity analysis revealed a crucial role of Δ7 and a terminal OH group in the regulation of CD3+ T cell proliferation. This is the first report of immunoregulatory activity for metabolites of this kind.

Towards the small and the beautiful: a small dibromotyrosine derivative from Pseudoceratina sp. sponge exhibits potent apoptotic effect through targeting IKK/NFκB signaling pathway.

A dibromotyrosine derivative, (1'R,5'S,6'S)-2-(3',5'-dibromo-1',6'-dihydroxy-4'-oxocyclohex-2'-enyl) acetonitrile (DT), was isolated from the sponge Pseudoceratina sp., and was found to exhibit a significant cytotoxic activity against leukemia K562 cells. Despite the large number of the isolated bromotyrosine derivatives, studies focusing on their biological mechanism of action are scarce. In the current study we designed a set of experiments to reveal the underlying mechanism of DT cytotoxic activity against K562 cells. First, the results of MTT cytotoxic and the annexin V-FITC/PI apoptotic assays, indicated that the DT cytotoxic activity is mediated through induction of apoptosis. This effect was also supported by caspases-3 and -9 activation as well as PARP cleavage. DT induced generation of reactive oxygen species (ROS) and the disruption of mitochondrial membrane potential (MMP) as indicated by flow cytometric assay. The involvement of ROS generation in the apoptotic activity of DT was further corroborated by the pretreatment of K562 cells with N-acetyl-cysteine (NAC), a ROS scavenger, which prevented apoptosis and the disruption of MMP induced by DT. Results of cell-free system assay suggested that DT can act as a topoisomerase II catalytic inhibitor, unlike the clinical anticancer drug, etoposide, which acts as a topoisomerase poison. Additionally, we found that DT treatment can block IKK/NFκB pathway and activate PI3K/Akt pathway. These findings suggest that the cytotoxic effect of DT is associated with mitochondrial dysfunction-dependent apoptosis which is mediated through oxidative stress. Therefore, DT represents an interesting reference point for the development of new cytotoxic agent targeting IKK/NFκB pathway.

Cytotoxic sesterterpenoids from a sponge Hippospongia sp.

One new pentacyclic sesterterpene, hippospongide A (1), and one new scalarane sesterterpenoid, hippospongide B (2), along with six previously reported known scalarane-type sesterterpenes (3-8), were isolated from a sponge Hippospongia sp. The structures of these compounds were elucidated on the basis of their spectroscopic data and comparison of the NMR data with those of known analogues. These metabolites are the first pentacyclic sesterterpene and scalarane-type sesterterpenes to be reported from this genus. Compounds 3-5 exhibited significant cytotoxicity against DLD-1, HCT-116, T-47D and K562 cancer cell lines.

Cytotoxic C21 and C22 terpenoid-derived metabolites from the sponge Ircinia sp.

One novel C21 terpenoidal natural product, ircinolin A (2), two new C22 furanoterpene metabolites, 15-acetylirciformonin B (3) and 10-acetylirciformonin B (4), and two known compounds, irciformonin B (1) and irciformonin F (5), were isolated from the sponge Ircinia sp. The structures of these compounds were elucidated on the basis of their spectroscopic data. Moreover, the absolute configuration of 1 was determined by Mosher's method. Among these metabolites, 2 is the first C21 terpenoid-derived metabolite to be reported from this genus. Compounds 1 and 3-5 exhibited significant cytotoxic activity against K562, DLD-1, HepG2, and Hep3B cancer cell lines.