1.Drug Resistance of Endocardial Endothelial Cells is Related to Higher Endogenous ABCG2.
Ajithkumar GS1, Vinitha A2, Binil Raj SS2, Kartha CC3. Cardiovasc Toxicol. 2015 Dec 11. [Epub ahead of print]
Endocardial endothelial cells (EECs), when compared with endothelial cells of arteries and veins, possess higher resistance to apoptosis-inducing anticancer agents. The mechanism of this resistance property is unknown. We have investigated the molecular mechanism, which contributes to increased cell survival capacity in EECs. We explored whether the resistance to apoptosis is associated with the cellular expression of ATP-binding cassette transporters such as P-glycoprotein, MRP-1, and ABCG2. We used primary and immortalized porcine endocardial endothelial cells (PEECs and hTERT PEECs) and compared the results with that in porcine aortic endothelial cells (PAECs), left atrioventricular valve endothelial cells (PVECs), and human umbilical vein endothelial cell line (EA.hy926). FACS and immunoblot analysis revealed a significantly higher expression of ABCG2 in PEECs and hTERT PEECs compared to PAECs, PVECs, and EA.hy926. Using apoptosis-inducing anticancer agents such as doxorubicin and camptothecin, through chromatin condensation assay and immunoblot analysis, we demonstrated a higher resistance to apoptosis in EECs compared to PAECs, PVECs, and EA.
2.Involvement of a Putative Bipartite Transit Peptide in Targeting Rice Pheophorbide a Oxygenase into Chloroplasts for Chlorophyll Degradation during Leaf Senescence.
Xie Q1, Liang Y2, Zhang J2, Zheng H3, Dong G4, Qian Q5, Zuo J6. J Genet Genomics. 2016 Mar 20;43(3):145-54. doi: 10.1016/j.jgg.2015.09.012. Epub 2016 Jan 8.
Leaf senescence is one of the major factors contributing to the productivity and the grain quality in crops. The regulatory mechanism of leaf senescence remains largely unknown. Here, we report the identification and characterization of a rice early senescence 1 (eas1) mutant, which displayed an early leaf senescence phenotype, accompanying by dwarfism and reduced tiller number, eventually leading to the reduction of grain yield. Map-based cloning revealed that the nuclear gene EAS1 encodes a pheophorbide a oxygenase (PaO), a key enzyme for chlorophyll breakdown. A highly conserved Thr residue of PaO was mutated into Ile in the eas1 mutant. Phylogenetic analysis indicates that PaO is an evolutionarily conserved protein, and EAS1 is 68% identical to the Arabidopsis ACCERLERATED CELL DEATH (ACD1) protein. Unlike ACD1 that contains a single transit peptide, EAS1 contains two putative transit peptides at its N-terminus, which are essential for its functionality, suggesting that targeting of EAS1 to the chloroplast is likely mediated by a putative bipartite transit peptide.
3.Cloning and characterization of the pepper CaPAO gene for defense responses to salt-induced leaf senescence.
Xiao HJ1,2, Liu KK3, Li DW4, Arisha MH5,6, Chai WG7, Gong ZH8. BMC Biotechnol. 2015 Oct 24;15:100. doi: 10.1186/s12896-015-0213-1.
BACKGROUND: Pheophorbide a oxygenase (PAO) is an important enzyme in the chlorophyll catabolism pathway and is involved in leaf senescence. It opens the porphyrin macrocycle of pheophorbide a and finally forms the primary fluorescent chlorophyll catabolite. Previous studies have demonstrated the function of PAO during cell death. However, the characterizaton of PAO during leaf senescence induced by environmental factors is not well understood.
4.A highly tumor-specific light-triggerable drug carrier responds to hypoxic tumor conditions for effective tumor treatment.
Park W1, Bae BC1, Na K2. Biomaterials. 2016 Jan;77:227-34. doi: 10.1016/j.biomaterials.2015.11.014. Epub 2015 Nov 11.
Light-triggered drug delivery is among the most investigated stimulus-response strategies and has been widely explored in cancer treatment. However, the limited specificity of light-triggered drug delivery reduces the therapeutic efficacy and causes considerable undesirable side effects. In this work, we demonstrate a highly tumor-specific light-triggerable drug carrier (H-LTDC) induced by a combination of internal (i.e., tumor hypoxia) and external stimuli (i.e., light). The doxorubicin (DOX)-loaded H-LTDC was self-assembled from type-1-reactive oxygen species (ROStype1)-mediated degradable chondroitin sulfate (CS) conjugated with a photosensitizer (PS), Pheophorbide-a, which has a spherical shape and a uniform size distribution. Under hypoxic conditions, ROSType1 was mainly generated due to the electron-rich sulfate groups in the polysaccharide backbone. The ROStype1 generated by H-LTDC allowed laser-triggered drug release at low oxygen concentrations.