Simulated microgravity induces DNA damage concurrent with impairment of DNA repair and activation of cell-type specific DNA damage response in microglial and glioblastoma cells.

Long-term spaceflights affect the structural changes in brain, alter motor or cognitive function and associated development of neuro-optic syndrome in astronauts. Studies addressing the impact of microgravity on brain cells are very limited. Herein, we employed microglial (CHME3) and glioblastoma (U87MG and A172) cells to study their molecular and functional adaptations under simulated microgravity (SMG) exposure. A reduction in cell viability and proliferation with decreased levels of PCNA were observed in these cells. SMG caused extensive DNA damage with an increase in γH2A.X (ser139) phosphorylation and differential activation/expression of DNA damage response (DDR) proteins including ATM, ATR, Chk1, Chk2 and p53 in all the three cell lines. Unlike CHME3, the ATM/Chk2-dependent DDR pathway was activated in glioblastoma cells suggesting a marked difference in the adaptation between normal and cancer cells to SMG. Five different classes of DNA repair pathways including BER, NER, MMR, NHEJ and HR were suppressed in both cell lines with the notable exception of NHEJ (Ku70/80 and DNA-PK) activation in U87MG cells. SMG induced mitochondrial apoptosis with increased expression of Bax, cleaved caspase-3 and cleaved poly-(ADP-ribose) polymerase, and reduced Bcl-2 level. SMG triggered apoptosis simultaneously via ERK1/2 and AKT activation, and inhibition of GSK3ß activity which was reversed by MEK1 and PI3K inhibitors. Taken together, our study revealed that microgravity is a strong stressor to trigger DNA damage and apoptosis through activation of ERK1/2 and AKT, and impairment of DNA repair capacity, albeit with a cell-type difference in DDR and NHEJ regulation, in microglial and glioblastoma cells.

Maximising the bioaccessibility of iron and zinc of a complementary food mix through multiple strategies.

The investigation was undertaken to maximise the bioaccessibility of iron and zinc of a complementary food mix by multiple approaches of dephytinisation and addition of organic acids. A wheat, pulse and oilseed protein flour mix was dephytinized by phytase activation and different thermal treatments. As the mineral content of the mix was low, the spray dried mix was fortified with different iron and zinc salts to identify the salt with the highest bioaccessibility in this matrix. Based on the percent bioaccessibility, the mix with sodium iron EDTA and zinc oxide was chosen for fortification. Bioaccessibility was enhanced by the addition of fruit powders and pure organic acids. Fruit powders showed a significant increase, but citric acid at a higher dose was beneficial in enhancing bioaccessible iron. The strategy of dephytinisation followed by fortification and the addition of fruit powders or organic acids is promising in alleviating iron and zinc deficiencies.