MARCKS mediates vascular contractility through regulating interactions between voltage-gated Ca2+ channels and PIP2.

Phosphatidylinositol 4,5-bisphosphate (PIP2) acts as substrate and unmodified ligand for Gq-protein-coupled receptor signalling in vascular smooth muscle cells (VSMCs) that is central for initiating contractility. The present work investigated how PIP2 might perform these two potentially conflicting roles by studying the effect of myristoylated alanine-rich C kinase substrate (MARCKS), a PIP2-binding protein, on vascular contractility in rat and mouse mesenteric arteries. Using wire myography, MANS peptide (MANS), a MARCKS inhibitor, produced robust contractions with a pharmacological profile suggesting a predominantly role for L-type (CaV1.2) voltage-gated Ca2+ channels (VGCC). Knockdown of MARCKS using morpholino oligonucleotides reduced contractions induced by MANS and stimulation of α1-adrenoceptors and thromboxane receptors with methoxamine (MO) and U46619 respectively. Immunocytochemistry and proximity ligation assays demonstrated that MARCKS and CaV1.2 proteins co-localise at the plasma membrane in unstimulated tissue, and that MANS and MO reduced these interactions and induced translocation of MARCKS from the plasma membrane to the cytosol. Dot-blots revealed greater PIP2 binding to MARCKS than CaV1.2 in unstimulated tissue, with this binding profile reversed following stimulation by MANS and MO. MANS evoked an increase in peak amplitude and shifted the activation curve to more negative membrane potentials of whole-cell voltage-gated Ca2+ currents, which were prevented by depleting PIP2 levels with wortmannin. This present study indicates for the first time that MARCKS is important regulating vascular contractility and suggests that disinhibition of MARCKS by MANS or vasoconstrictors may induce contraction through releasing PIP2 into the local environment where it increases voltage-gated Ca2+ channel activity

Recent Advances in Sugarcane Industry Solid By-Products Valorization

Sugarcane is among the leading agricultural crop cultivated in tropical regions of the world. Industrial processing of sugarcane generates sugar; as well as various solid wastes (i.e. sugarcane bagasse, pressmud). Improvement of biotechnology in industrial level, offers opportunities for economic utilization of these solid residues. In the last few decades, sugarcane bagasse and pressmud have been explored in the theme of lignocellulosic bioconversion. The recalcitrance of biomass is a major drawback towards successful exploitation of lignocellulosic residues. Pretreatment by suitable/efficient processes can overcome this limitation. In this regards; physical, chemical and biological treatment systems are brought into our perspective. Chemical and physicochemical methods are capital-intensive but not environment-friendly, in contrast, method like biological treatment is eco-friendly but extremely slow. There are still major technological and economic challenges need to be addressed; e.g. bioprospecting, established more reliable genetically modified microorganisms, upgrade gene cloning and sequencing processes, yield improvement at large scale etc. Productions of value-added products from these solid wastes are discussed in such a way that pinpoints the most recent trends and the future directions. Biofuels, enzymes, organic acids and bio-sorbents production draw a clear sketch of the current and future bio-based products. Nano-biotechnology and genetic engineering could be future trends to improved processes and products. This review serves as a valuable reference material for a wide range of scientists and technologists in the relevant fields