Elevated levels of protein phosphatase 1 and phosphatase 2A may contribute to cardiac dysfunction in diabetes

AbstractAlthough protein phosphorylation and dephosphorylation are known to regulate the activities of different enzymes, sufficient information on the role of dephosphorylation in cardiac function is not available. Since protein phosphatases mediate dephosphorylation, it is possible that cardiac dysfunction induced by diabetes may be due to alterations in the activities of these enzymes. We therefore determined cardiac protein phosphatase activity as well as protein contents of phosphatase 1 and phosphatase 2A in diabetic animals. For this purpose, rats were made diabetic by administering a single intravenous injection of streptozotocin (65 mg/kg body weight) and hearts were examined after 1, 2, 3, 4 and 8 weeks. Some of the 4-week diabetic animals received subcutaneous injections of insulin (3 U/day) for a further period of 4 weeks. Cardiac dysfunction was evident after 2 weeks of inducing diabetes and deteriorated further with time. A significant increase in protein phosphatase activity appeared after 1 week and persisted until 8 weeks. Increased protein phosphatase activity in the diabetic heart was associated with a corresponding increase in the protein contents of both phosphatase 1 and phosphatase 2A. Insulin treatment partly prevented the changes observed in diabetic animals. The results suggest that increased protein phosphatase activities and subsequent enhanced protein dephosphorylation may play a role in diabetes-induced cardiac dysfunction

Signaling interactions in the adrenal cortex

The major physiological stimuli of aldosterone secretion are angiotensin II (AII) and extracellular K+ whereas cortisol production is primarily regulated by corticotrophin (ACTH) in fasciculata cells. AII triggers Ca2+ release from internal stores that is followed by store-operated and voltage-dependent Ca2+ entry whereas K+-evoked depolarisation activates voltage-dependent Ca2+ channels. ACTH acts primarily through the formation of cAMP and subsequent protein phosphorylation by protein kinase A. Both Ca2+ and cAMP facilitate the transfer of cholesterol to mitochondrial inner membrane. The cytosolic Ca2+ signal is transferred into the mitochondrial matrix and enhances pyridine nucleotide reduction. Increased formation of NADH results in increased ATP production whereas that of NADPH supports steroid production. In reality, the control of adrenocortical function is a lot more sophisticated with second messengers crosstalking and mutually modifying each other’s pathways. Cytosolic Ca2+ and cGMP are both capable of modifying cAMP metabolism whilst cAMP may enhance Ca2+ release and voltage-activated Ca2+ channel activity. Besides, mitochondrial Ca2+ signal brings about cAMP formation within the organelle and this further enhances aldosterone production. Maintained aldosterone and cortisol secretion are optimized by the concurrent actions of Ca2+ and cAMP, as exemplified by the apparent synergism of Ca2+ influx (inducing cAMP formation) and Ca2+ release during response to AII. Thus, cross-actions of parallel signal transducing pathways are not mere intracellular curiosities but rather substantial phenomena which fine-tune the biological response. Our review focuses on these functionally relevant interactions between the Ca2+ and the cyclic nucleotide signal transducing pathways hitherto described in the adrenal cortex

Characterisation of the canine cardiac sarcolemma in experimental myocardial ischemia

The cardiac sarcolemma was characterized in 13 normal and 11 ischemic dog hearts by enzyme analysis and compositional assays. Significant decreases in the activities of the sodium-potassium and calcium pumps and structural compositional disturbances were observed in ischemia. High concentrations of oleic acid, a fatty acid and palmitoyl carnitine, a fatty acid intermediate caused inhibition of the enzyme pump activities of the normal sarcolemma. Thus, ischemia results in the functional impairment of the sarcolemma. Accumulation of fatty acid and fatty acid intermediates, occurring in myocardial ischemia, could be an underlying mechanism

Health Benefits of Cereal Grain- and Pulse-Derived Proteins

Pulses and whole grains are considered staple foods that provide a significant amount of calories, fibre and protein, making them key food sources in a nutritionally balanced diet. Additionally, pulses and whole grains contain many bioactive compounds such as dietary fibre, resistant starch, phenolic compounds and mono- and polyunsaturated fatty acids that are known to combat chronic disease. Notably, recent research has demonstrated that protein derived from pulse and whole grain sources contains bioactive peptides that also possess disease-fighting properties. Mechanisms of action include inhibition or alteration of enzyme activities, vasodilatation, modulation of lipid metabolism and gut microbiome and oxidative stress reduction. Consumer demand for plant-based proteins has skyrocketed primarily based on the perceived health benefits and lower carbon footprint of consuming foods from plant sources versus animal. Therefore, more research should be invested in discovering the health-promoting effects that pulse and whole grain proteins have to offer

Analyses of Fatty Acids, Proteins, Ascorbic Acid, Bioactive Phenolic Compounds and Antioxidant Activity of Canadian Barley Cultivars and Elite Germplasm

Barley (Hordeum vulgare L.) grain is rich in fiber and antioxidant phytochemicals, including fatty acids, proteins, phenolic compounds, vitamins, and minerals, that offer various health benefits. Research on identifying different barley genotypes based on their health attributes is very limited. In this study, we performed an analysis of fatty acids, proteins, ascorbic acid, phenolic compounds, and antioxidant activity of several Canadian barley cultivars and elite breeding lines. Linoleic acid (C18:2) was the predominant fatty acid present in the tested barley cultivars. The cultivar CDC Bold contained the highest amount of ascorbic acid, while the highest protein content was in CDC Mindon. An assessment of the free and bound phenolic compounds of barley grains showed quantitative changes among different genotypes of Canadian barley. Catechin is the most abundant molecule in free phenolics, while ferulic acid and para-coumeric acid are the most abundant in bound phenolics. Ferulic acid and vanillic acid were molecules detected in the soluble free fraction of all genotypes. Para-coumeric acid was detected only in genotypes such as CDC Copeland, CDC Bold, Lowe, and elite breeding Line 5 of both free and bound fractions of barley. Breeding Line 5 had the lowest antioxidant activity. An analysis of the above molecules and parameters of Canadian barley would help to uncover potential biomarkers in order to distinguish individual barley genotypes

Comparative and Combinatorial Effects of Resveratrol and Sacubitril/Valsartan alongside Valsartan on Cardiac Remodeling and Dysfunction in MI-Induced Rats

The development and progression of heart failure (HF) due to myocardial infarction (MI) is a major concern even with current optimal therapy. Resveratrol is a plant polyphenol with cardioprotective properties. Sacubitril/valsartan is known to be beneficial in chronic HF patients. In this study, we investigated the comparative and combinatorial benefits of resveratrol with sacubitril/valsartan alongside an active comparator valsartan in MI-induced male Sprague Dawley rats. MI-induced and sham-operated animals received vehicle, resveratrol, sacubitril/valsartan, valsartan alone or sacubitril/valsartan + resveratrol for 8 weeks. Echocardiography was performed at the endpoint to assess cardiac structure and function. Cardiac oxidative stress, inflammation, fibrosis, brain natriuretic peptide (BNP), creatinine and neutrophil gelatinase associated lipocalin were measured. Treatment with resveratrol, sacubitril/valsartan, valsartan and sacubitril/valsartan + resveratrol significantly prevented left ventricular (LV) dilatation and improved LV ejection fraction in MI-induced rats. All treatments also significantly reduced myocardial tissue oxidative stress, inflammation and fibrosis, as well as BNP. Treatment with the combination of sacubitril/valsartan and resveratrol did not show additive effects. In conclusion, resveratrol, sacubitril/valsartan, and valsartan significantly prevented cardiac remodeling and dysfunction in MI-induced rats. The reduction in cardiac remodeling and dysfunction in MI-induced rats was mediated by a reduction in cardiac oxidative stress, inflammation and fibrosis