Revisiting the role of phospholipases in alzheimer's: crosstalk with processed food.

Phospholipases such as phospholipase-A, phospholipase-B, phospholipase-C and phospholipase-D are important functional enzymes of the cell membrane responsible for a variety of functions such as signal transduction, production of lipid mediators, metabolite digestion and playing a pathological role in central nervous system diseases. Phospholipases have shown an association with Alzheimer's disease and these enzymes have found a correlation with several metabolic pathways that can lead to the activation of inflammatory signals via astrocytes and microglial cells. We also highlighted unhealthy practices like smoking and consuming processed foods, rich in nitroso compounds and phosphatidic acid, which contribute to neuronal damage in AD through phospholipases. A few therapeutic approaches such as the use of inhibitors of phospholipase-D,phospholipase A2 as well as autophagy-mediated inhibition have been discussed to control the onset of AD. This paper serves as a crosstalk between phospholipases and their role in neurodegenerative pathways as well as their influence on other biomolecules of lipid membranes, which are acquired through unhealthy diets and possible methods to treat these anomalies occurring due to their metabolic disorder involving phospholipases acting as major signaling molecules.

Crataegus songarica methanolic extract accelerates enzymatic status in kidney and heart tissue damage in albino rats and its in vitro cytotoxic activity.

CONTEXT: Crataegus songarica K. Koch (Rosaceae) has been used in folk medicine to treat various diseases. OBJECTIVE: This study evaluates the effect of C. songarica methanol extract on the kidney and heart tissue damage of albino rats, and to determine cytotoxic activity of various extracts of songarica on various human cancer cell lines. MATERIALS AND METHODS: Rats were divided into six groups, Group I received water only; Group II received CCl4 (1 mL/kg b wt) intraperitoneal; C. songarica extract (at doses of 100, 200 and 300 mg/kg b wt) orally for 15 days. Cytotoxic activity was determined by SRB method using MCF-7, HeLa, HepG2, SF-295, SW480 and IMR-32 cell lines. RESULTS: Compared with CCl4 group, administration of C. songarica extract at the dose of 300 mg/kg b wt, significantly decreases serum creatinine (59.74%), urea (40.23%) and cholesterol (54 mg/dL), MDA (0.007 nmol/mg protein) in kidney and (0.025 nmol/mg protein) in heart tissue, along with evaluation of GSH (209.79 ± 54.6), GR (111.45 ± 2.84), GPx (94.01 ± 14.80), GST (201.71) in kidney tissue and GSH (51.47 ± 1.47), GR (45.42 ± 6.69), GPx (77.19 ± 10.94), GST (49.89) in heart tissue. In addition, methanol, ethanol and ethyl acetate extracts exhibited potent anticancer activity on six cancer cell lines with IC50 values ranging from 28.57 to 85.106 µg/mL. DISCUSSION AND CONCLUSION: Crataegus songarica methanol extract has a potential antioxidant effect as it protects the kidney and heart tissue against CCl4-induced toxicity, prevents DNA damage and showed strong anticancer activity.

A new method for determining the constant-pressure heat capacity change associated with the protein denaturation induced by guanidinium chloride (or urea).

Differential scanning calorimetry (DSC) provides authentic and accurate value of DeltaC(p)(X), the constant-pressure heat capacity change associated with the N (native state)<-->X (heat denatured state), the heat-induced denaturation equilibrium of the protein in the absence of a chemical denaturant. If X retains native-like buried hydrophobic interaction, DeltaC(p)(X) must be less than DeltaC(p)(D), the constant-pressure heat capacity change associated with the transition, N<-->D, where the state D is not only more unfolded than X but it also has its all groups exposed to water. One problem is that for most proteins D is observed only in the presence of chemical denaturants such as guanidinium chloride (GdmCl) and urea. Another problem is that DSC cannot yield authentic DeltaC(p)(D), for its measurement invokes the existence of putative specific binding sites for the chemical denaturants on N and D. We have developed a non-calorimetric method for the measurements of DeltaC(p)(D), which uses thermodynamic data obtained from the isothermal GdmCl (or urea)-induced denaturation and heat-induced denaturation in the presence of the chemical denaturant concentration at which significant concentrations of both N and D exist. We show that for each of the proteins (ribonuclease-A, lysozyme, alpha-lactalbumin and chymotrypsinogen) DeltaC(p)(D) is significantly higher than DeltaC(p)(X). DeltaC(p)(D) of the protein is also compared with that estimated using the known heat capacities of amino acid residues and their fractional area exposed on denaturation.

Testing the paradigm that the denaturing effect of urea on protein stability is offset by methylamines at the physiological concentration ratio of 2:1 (urea:methylamines).

The intra- and extracellular urea concentration in many organisms is sufficiently high to destabilize (inhibit) many proteins, yet organisms survive and function. The generally accepted explanation is the counteracting hypothesis, which holds that methylamines stabilize proteins and oppose the deleterious effect of urea. The two osmolytes are typically found at 2:1 concentration ratio (urea:methylamine) under physiological conditions. Does this mean that this ratio holds for all proteins in a cell? The present study tests the counteracting hypothesis by determining the effects of urea and methylamines (trimethylamine N-oxide and sarcosine), singly and in combination at a concentration ratio of 2:1 (urea:methylamine) on the thermal denaturation equilibrium, native state<-->denatured state of three different proteins (alpha-lactalbumin, lysozyme and Ribonuclease-A). We show here that the molar concentration of a methylamine required to offset the denaturing effect of urea at a given concentration is different for different proteins.