Objective(s): 4-Phenyl butyric acid (4-PBA) is a Chaperone-mediated autophagy (CMA) inducer, which eliminates unnecessary and damaged cellular components through lysosomal enzymes. It could reduce misfolded and unfolded proteins produced after myocardial infarction (MI) and can improve cardiac function. We aimed to investigate the effect of 4-PBA on isoproterenol-induced MI in rats. Materials and Methods: Isoproterenol (100 mg/kg) was injected subcutaneously for two consecutive days simultaneous with an intraperitoneal (IP) injection of 4-PBA at 20, 40, or 80 mg/kg at 24-hr intervals for five days. On day 6, hemodynamic parameters, histopathological changes, peripheral neutrophil count, and total anti-oxidant capacity (TAC) were evaluated. The expression of autophagy proteins was measured by using western blotting. 4-PBA significantly improved post-MI changes in hemodynamic parameters. Results: Histological improvement was found in 4-PBA 40 mg/kg (P<0. 05). The neutrophil count in the peripheral blood significantly decreased in the treatment groups compared with isoproterenol. Furthermore, 4-PBA at 80 mg/kg significantly increased the serum TAC compared with isoproterenol (P<0. 001). Western blotting showed a significant decrease in the P62 level (P<0. 05) of 40 and 80 mg/kg 4-PBA treated groups. Conclusion: This study demonstrated that 4-PBA could have a cardio-protective effect against isoproterenol-induced MI, which can be due to autophagy modulation and oxidative stress inhibition. Obtaining effective results in different doses shows the need for an optimum degree of cell autophagic activity.

Epigenetic alterations, including DNA acetylation, hypermethylation and hypomethylation, and the associated transcriptional changes of the affected genes are central to the evolution and progression of various human cancers, including pancreatic cancer. Cancer-associated epigenetic alterations are attractive therapeutic targets because such epigenetic alterations, unlike genetic changes, are potentially reversible. Several drugs that target epigenetic alterations, including inhibitors of histone deacetylase (HDAC) and DNA methyltransferase (DNMT), are currently approved for treatment of hematological malignancies and are available for clinical investigation in solid tumors. Histone deacetylases (HDACs) is well known to be associated with tumorigenesis through epigenetic regulation. HDACs comprise an ancient family of enzymes that play crucial roles in numerous biological processes and HDACs are found to be over expressed in many tumor types. Its inhibitors (HDACIs) induce differentiation and apoptosis of tumor cells. In addition, the activity of heat shock proteins (Hsps) can be regulated by HDACs. Hsps exist in many types of cells and these proteins can prevent aggregation and formation of toxic inclusion. Hsps are major molecular Chaperones in prokaryotic and eukaryotic cells. This review summarizes mechanisms of histone deacetylase inhibitors action on Hsps and will describe the regulation of major cellular Chaperones and heat shock factors by HDACmediated deacetylation.

Protein aggregation and precipitation is associated with many debilitating diseases including Alzheimer's, Parkinson's, and light-chain amyloidosis. b-Casein, a member of the casein family, has been demonstrated to exhibit Chaperone-like activity to protect protein form aggregation. Hofmeister salts (lyotropice series) are a class of ions which have an effect on the solubility and also the stability of proteins. In this study, using a range of Hofmeister salts (Na2SO4, NaCl and KSCN) altered the rate of aggregation and precipitation of a- lactalbumin. The rate of aggregation of a-lactalbumin increased in the presence of all the added salts. However, Na2SO4 had the greatest effect on the rate of aggregation of a-lactalbumin. b-Casein effectively prevented the aggregation of a-lactalbumin but not as well as in the presence of the salt. Interestingly, in the presence of Na2SO4, b-casein was the poorer Chaperone toward aggregation of a-lactalbumin compare to in the presence of NaCl and KSCN. Our result showed that all salts had structural effects on the b-casein which affects its Chaperone ability. In summary, structural change and kinetic factors maybe be determinant the poorer Chaperone ability of b-casein in the presence of salts.

Overexpression of recombinant proteins in Escherichia coli results in inclusion body formation, and consequently decreased production yield and increased production cost. Co-expression of Chaperon systems accompanied by recombinant protein is a general method to increase the production yield. However, it has not been successful enough due to imposed intense stress to the host cells. The aim of this study was to balance the rate of protein production and the imposed cellular stresses using a two-step expression system. For this purpose, in the first step, green fluorescent protein (GFP) was expressed as a recombinant protein model under control of the T7-TetO artificial promoter-operator, accompanied by Dnak/J/GrpE Chaperon system. Then, in the next step, TetR repressor was activated automatically under the control of the stress promoter ibpAB and suppressed the GFP production after accumulation of inclusion bodies. Thus in this step incorrect folded proteins and inclusion bodies are refolded causing increased yield and solubility of the recombinant protein and restarting GFP expression again. Total GFP, soluble and insoluble GFP fractions, were measured by Synergy H1 multiple reader. Results showed that expression yield and soluble/insoluble ratio of GFP have been increased 5 and 2. 5 times using this system in comparison with the single step process, respectively. The efficiency of this system in increasing solubility and production yield of recombinant proteins was confirmed. The two-step system must be evaluated for expression of various proteins to further confirm its applicability in the field of recombinant protein production.

Background: Analysis of many proteins produced during the transition into the stationary phase and under stress conditions (including starvation stress) demonstrated that a number of novel proteins were induced in common to each stress and could be the reason for cross-protection in bacterial cells. It is necessary to investigate the synthesis of these proteins during different stress conditions. Methods: The changes in protein profile of Flexibacter chinensis at various stages of the starvation process and the other stresses were investigated using two-dimensional gel electrophoresis which has proven to be a powerful tool for investigation of the changes in protein profiles under such conditions. Results: Most starvation proteins were synthesized during the early stationary phase and many of these proteins remained during long-term starvation. Some of these proteins were transiently synthesized. The sequencing result of one of the proteins showed that there was a 62.5% identity in 8 amino acids overlapped with the 5’ residue of a 10 kDa Chaperon protein which is known to be involved in the starvation stress response in other organisms. Conclusion: There are many proteins synthesized in common with many stresses in Flexibacter chinensis. Some of these proteins must play a major role in the stability of the cell under different stresses.