Differential crosstalk between global DNA methylation and metabolomics associated with cell type specific stress response by pristine and functionalized MWCNT.

The present study endeavored to evaluate the comprehensive mechanisms of MWCNT-induced toxicity with particular emphasis on understanding cell specificity in relation to surface functionalization of MWCNT. Following treatment with differentially functionalized (hydroxylation/carboxylation) MWCNT on human bronchial epithelial (BEAS-2B) and human hepatoma (HepG2) cell lines, intracellular uptake, various toxicological end points, global metabolomics profiling and DNA methylation were evaluated. Herein, the comparative in vitro studies ascertained that surface functionalization diminished the toxic potentiality of MWCNT in respect of their pristine counterpart. The surface enhanced Raman scattering with dark-field microscopy attested the intracellular uptake of functionalized-MWCNT, but not the pristine one. The MWCNT's exposure caused alterations in stress responses (oxidative stress, inflammation, profibrosis, DNA damage-repair), differential mode of gene expressions, global metabolomics and DNA methylation status (DNMT3B dependent hypo-methylation in BEAS-2B cells and hyper-methylation in HepG2 cells) in a cell type specific and surface functionalization dependent manner. The alterations in particular metabolites (choline, betaine, succinate etc.) and distinct DNA methylation crosstalk patterns are the possible underlying mechanisms of differential mode of gene expressions and cell type specificity of MWCNT. This study provides preliminary evidence of epigenetic modifications and global metabolomics profiling which might be translated for risk assessment of MWCNT.

Crosstalk between Fas and JNK determines lymphocyte apoptosis after ionizing radiation.

Radiation simultaneously activate Fas and JNK pathway in lymphocytes but their precise interaction is not clearly understood. Activation of Fas pathway is required for radiation induced apoptosis, however induction of JNK pathway may or may not contribute in apoptosis. Here we report that Fas, Fas associated death domain and total JNK are activated in a dose- and time-dependent radiation exposure. A biphasic pattern of phospho-JNK was found at lower doses (1 and 2 Gy), however at higher doses of radiation phospho-JNK was continuously activated. Interestingly, Fas ligand expression remained biphasic at all the doses of radiation. Our results suggest that the Fas pathway is the major player in radiation-induced apoptosis, with JNK playing a contributory role. We also observed that Fas ligand expression by radiation is dependent on JNK activation. We also propose that radiation activates JNK pathway, but sustained activation is required for maximal induction of apoptosis at later times. Our findings define a mechanism for crosstalk between JNK and Fas pathway in radiation-induced apoptosis, which may lead to the development of new therapeutic strategies.

Light signals, phytochromes and cross-talk with other environmental cues.

Plants have evolved highly complex sensory mechanisms to monitor their surroundings and adapt their growth and development to the prevailing environmental conditions. The integration of information from multiple environmental cues enables the co-ordination of development with favourable seasonal conditions and, ultimately, determines plant form. Light signals, perceived via the phytochrome, cryptochrome and phototropin photoreceptor families, are especially important environmental signals. Redundancy of function among phytochromes and their interaction with blue light photoreceptors enhance sensitivity to light signals, facilitating the accurate detection of, and response to, environmental fluctuations. In this review, current understanding of Arabidopsis phytochrome functions will be summarized, in particular, the interactions among the phytochromes and the integration of light signals with directional and temperature sensing mechanisms.