Nd(III)-induced rice mitochondrial dysfunction investigated by spectroscopic and microscopic methods.

The production capacity and yield of neodymium (Nd) in China have ranked the first in the world. Because of its unique biophysical and biochemical properties, Nd compounds have entered into the agricultural environment greatly to promote plant growth. Mitochondria play a crucial role in respiration and metabolism during the growth of plants. However, little is known about the mechanism by which Nd act at the mitochondrial level in plant cells. In this study, rice mitochondrial swelling, collapsed transmembrane potential and decreased membrane fluidity were examined to be important factors for mitochondria permeability transition pore (mPTP) opening induced by Nd(III). The protection of cyclosporin A (CsA) and dithiothreitol (DTT) could confirm that Nd(III) could trigger mPTP opening. Additionally, mitochondrial membrane breakdown observed by TEM and the release of cytochrome c (Cyt c) could also elucidate the mPTP opening from another point of view. At last, the study showed that Nd(III) could restrain the mitochondrial membrane lipid peroxide, so it might interact with anionic lipid too. This detection will be conductive to the safe application of Nd compounds in agriculture and food industry.

Synthesis and pharmacological characterization of glucopyranosyl-conjugated benzyl derivatives as novel selective cytotoxic agents against colon cancer.

Glucopyranosyl-conjugated benzyl derivatives containing a [1,2,3]-triazole linker were synthesized. Benzyl served as an important pharmacophore in anti-cancer compounds. Compound 8d inhibited the proliferation of colorectal cancer cells with the potency comparable to 5-fluorouracil (5-FU) with improved selectivity towards cancer cells. The antiproliferative activity of 8d is achieved through triggering apoptotic cell death.

Chitosan quaternary ammonium salt induced mitochondrial membrane permeability transition pore opening study in a spectroscopic perspective.

Chitosan is non-toxic, biodegradable and biocompatible. However, it is insoluble in water, which limits its applications in biomedical areas. Hydroxypropyltrimethyl ammonium chloride chitosan (HACC), a chitosan derivative, can be dissolved in physiological condition and has been widely used in the field of biomedicine and bioengineering. The biological effect of HACC has been extensively studied. However, it is rarely investigated at the subcellular level. To study the biological effect of HACC, mitochondria, energy-producing organelles in eukaryotes, were chosen as a model. The investigation mainly focused on the changes of mitochondrial membrane property in the presence of HACC. Results showed that HACC can induce the collapse of mitochondrial transmembrane potential (∆Ψm), the increase in mitochondrial membrane swelling and the decrease of mitochondrial membrane fluidity, demonstrating that mitochondrial membrane permeability transition pore (mPTP) opening happened. Possible mechanism of mPTP opening investigation indicated that it was occurred in a typical model. In addition, HACC can induce the release of cytochrome C (Cyt c) and affect the respiratory activity of mitochondria. The study will provide a lot of important information on biosafety evaluation of HACC.

Microcalorimetric and microscopic studies of the effect of chitosan quaternary ammonium salt on mitochondria.

Chitosan quaternary ammonium salt (HACC) has been regarded as an effective biomedical carrier with good application because of its good water-solubility, high cationic potential and strong cell adhesion. Mitochondria are important organelle involved in ATP production and are the center of energy metabolism. In this work, we firstly investigated the effect of HACC on the thermogenic curve of isolated mitochondrial metabolism by microcalorimetry. The results showed that different concentration of HACC had great influence on the mitochondrial energy metabolism. Specifically, low level of HACC stimulated the metabolic activity of mitochondria and the inhibition was found with high concentration of HACC. Then, the effect of HACC on mitochondrial respiratory chain was studied, which was consistent with the results of microcalorimetry. Finally, the alteration of mitochondrial structure induced by HACC was observed and it showed that the membrane of mitochondria was dramatically damaged. These new findings can help us deeply understand the influence and action mechanism of HACC in the metabolic process and provide theoretical and practical foundation for the biosafety of HACC as a medical carrier.

Effect of orally administered hydroxypropyl chitosan on the levels of iron, copper, zinc and calcium in mice.

Two hydroxypropyl chitosan HPCS samples (HPCS1 Mw 1.6 × 10(5), HPCS2 Mw 3.5 × 10(4)) were prepared by the reaction of chitosan with propylene oxide under alkali conditions. The median lethal dose of the hydroxypropyl chitosan was greater than 10 g/kg for the laboratory mice. HPCS1 at the 0.1%, 1.0%, 1.5% and HPCS2 at the 1.0% level in diets were used to feed the mice for 90 days respectively. No pathological symptoms, clinical signs or deaths were observed for all mice. The weights of the mice in HPCS groups and control group had no significant difference. The levels of Fe, Cu, Zn and Ca in the mice were measured by atomic absorption spectrophotometry. HPCS had no significant effect on the levels of Fe, Cu, Zn and Ca in the tested mice's livers and hearts. However, hydroxypropyl chitosan at high dose exhibited inhibitory effects on the levels of Fe, Zn and Ca in some organizations.

Antibacterial evaluation of novel organoarsenic compounds by the microcalorimetric method.

Antibacterial activities of novel organoarsenic compounds As(III)-containing Schiff bases on Escherichia coli (CCTCCAB91112) were investigated by microcalorimetry in this study. The experimental result showed that the arsenic(III)-containing Schiff bases at micromolar concentration exhibit strong inhibition on the E. coli. Specifically, the growth rate constant k decreased, and the generation time t G and the inhibitory ratio I (percentage) increased with the increased dose of the arsenicals as inhibitors. All of the arsenicals display the feature of considerable lag phase inhibition on the cell growth. The compound 4-(4-bromobenzaliminyl)phenylarsenoxide makes the lag phase of E. coli cell growth cycles to reach 650 min at 5 µmol/L. The compounds with donating electron groups at aromatic ring B have lower IC50 to present higher antibacterial activity. The compound 4-(4-hydroxyl-3-methoxylbenzaliminyl)phenylarsenoxide has the lowest IC50 (1.82 µmol/L) to show the strongest antibacterial activity among them.

High concentration of gadolinium ion modifying isolated rice mitochondrial biogenesis.

Mitochondria play an important role in plant growth and development, cooperating with the endoplasmic reticulum and nucleus. Gadolinium, one of the rare earth elements, is an inhibitor of stretch-activated calcium channels located on the endoplasmic reticulum and plasma membrane and has no effect on nuclear calcium variation in plant cells. We analyzed the effects of Gd3+ on mitochondria function by monitoring mitochondrial swelling, changes of membrane fluidity, and transmembrane potential collapse and by observing mitochondrial ultrastructure. We found that high concentration of Gd3+ induces rice mitochondrial dysfunction through mitochondrial permeability transition (MPT). The protection of DTT and EDTA demonstrate that Gd3+ blocks the inner membrane ion channel through thiol chelation.

Microcalorimetric studies of the effect of cerium (Ш) on isolated rice mitochondria fed by pyruvate.

Mitochondria were isolated from the hybrid rice Xiangzaoxian 31, then the effects of low and high concentrations of Ce (Ш) on metabolism of mitochondria fed by pyruvate were investigated respectively, by microcalorimetry and oxygen electrode method The thermogenic curve of mitochondria without Ce (Ш) could be divided into three parts: activity recovery phase, stationary phase and decline phase. And the thermokinetic parameters have been calculated through the metabolic thermogenic curves. With addition of different concentrations of Ce (Ш), the results demonstrated that low levels of cerium ion stimulated the metabolic activity of energized mitochondria and the inhibition was discovered with high concentrations of Ce (Ш). At the same time, it is shown that the effect in respiration correspond to the effect on mitochondrial metabolism on addition of different concentrations of Ce (Ш). Moreover, the addition of low and high concentrations of Ce (Ш) had no obvious effect on the total heat output (Q). The concentration-dependent effect of Ce (Ш) on metabolism of mitochondria is similar to plant growth response to rare earth elements (Hormesis effect).

Ce(III)-induced rice mitochondrial permeability transition investigated by spectroscopic and microscopic studies.

Cerium has been widely used as fertilizer and feed additives in agriculture, but it might finally impair human health by food chain accumulation with its dosage increased in environmental and crops samples. To resolve the conflict, we investigated the effects of Ce(III) on isolated rice mitochondrial permeability transition (MPT) by examining mitochondrial swelling, transmembrane potential, membrane fluidity with spectroscopy, and observing the mitochondrial ultrastructure, meanwhile, the interaction site(s) and mechanism between Ce(III) and mitochondria were also studied. The results showed that the low level of Ce(III) had little effect on rice MPT, however, the higher level of Ce(III) could induce rice MPT, and the thiol (-SH) groups of membrane proteins (defined as "S" site) matched by Ce(III)-triggered rice MPT pore opening.