Molecular and cellular regulatory roles of sirtuin protein.

Sirtuins (SIRT) are unique posttranslational modification enzymes that utilize NAD + as co-substrate to remove acyl groups from lysine residues. SIRT act on variety of substrates and impact major metabolic process. All seven members of SIRT family are unique and targets wide range of cellular proteins in nucleus, cytoplasm, and mitochondria for post-translational modification by acetylation (SIRT1, 2, 3, and 5) or ADP-ribosylation (SIRT4 and 6). Each member of SIRT family is distinct. SIRT2 was first to be discovered that incited research on mammalian SIRT. Enzymatic activities of SIRT 4 are yet to be elucidated while only SIRT7 is localized in nucleoli that govern the transcription of RNA polymerase I. SIRT 5 and 6 exhibit weakest deacetylase activity. Out of all SIRT analogs, SIRT1 is identified as nutrient sensor. Increased expression of only SIRT3 is linked with longevity in humans. Since SIRT is regulated by the bioenergetic state of the cell, nutrition impacts it but very few studies about diet-mediated effect on SIRT are reported. The present review elaborates distribution, specific biological role and prominent effect of all SIRT on vital human tissue along with highlighting need to trace molecular mechanisms and identifying foods that may augment it beneficially.

The Underexplored Dimensions of Nutritional Hormesis.

PURPOSE OF REVIEW: Hormesis is biphasic response wherein low and high doses of chemical and nutrient confer beneficial and toxic effects respectively, typically in a U-shaped manner. Hormesis is intricately related to bioenergetic state of a cell, and therefore, nutrition impacts it. Excessive nutrition can halt the endogenous antioxidant synthesis leading to cytotoxic effects. While low and optimum doses of the same bring about hormetic stimulation that can exalt the antioxidant response and reduce susceptibility towards degenerative diseases. The sirtuin family of proteins is triggered by mild stress of calorie restriction and exerts hormesis. Similarly, several phytochemicals and micronutrients are known to bring about health benefits at optimum dose and deleterious effects at high doses. Despite this attribute, nutritional hormesis is not very well researched upon because the magnitude of hormetic effect observed is generally quite modest. There is no precise regulation of optimal intake of certain foods to witness hormesis and no characterization of any biomarker that reports stress responses at various doses above or below optimal intakes. There is a major gap in research between nutrition and hormesis being affected by sirtuin family of proteins, phytochemicals, and micronutrients. RECENT FINDINGS: Mild stress of calorie restriction elevates sirtuin protein and effect of sirtuin protein on hormesis has been recently reported. More foods that enhance sirtuin protein, phytochemicals, and micronutrients need to be explored in relation to hormesis and associated health benefits.

Buckwheat-enriched diet alleviates bisphenol A mediated oxidative stress via modulation of sirtuin 1 and antioxidant status in experimental rats.

Present study investigated effect of dietary buckwheat in alleviating bisphenol A (BPA) mediated oxidative stress, concomitant sirtuin1 levels in serum, stomach, and liver of rats. Experimental group A and B ingested standard diet, C and D consumed buckwheat (30%); group A and C drank normal water, B and C had BPA contamination (10 mg L-1). Sirtuin1 mean B/A ratio nearing unity in all tissues reveals inertness of BPA towards sirtuin1. Dietary buckwheat improved sirtuin1 levels both in normal (mean C/A ratio of serum, 1.65; liver, 1.24; stomach, 1.78) and BPA fed state (mean D/B ratio of serum, 1.9; liver, 1.26; stomach, 1.75). Buckwheat augmented antioxidant status in BPA fed rats as seen in mean D/B ratio of serum (catalase, 2.4; glutathione reductase (GR), 1.33; Thiols, 1.2), liver (catalase, 2; GR, 2.5; Thiols, 1.36) and stomach (catalase, 1.31; GR, 1.5; Thiols, 1.33). Therefore, buckwheat counters BPA-led oxidative stress and modulates sirtuin1.

A noninvasive and qualitative bioluminescent assay for express diagnostics of athletes' responses to physical exertion.

Upcoming professional sports authorities seek rapid noninvasive biosensing tools for regular monitoring of athletes' physiological states. The analysis of saliva through luminescence-based biosensors has been perceived as a suitable candidate for such purposes. The present study reports a qualitative bioluminescence assay based on a coupled enzyme system that consists of bacterial luciferase (BLuc) and nicotinamide adenine dinucleotide (NADH):flavin mononucleotide (FMN) oxidoreductase (Red), BLuc-Red, for the express diagnostics of athletes' stress levels before and after physical exertion. The volunteers who participated in the study were grouped as freestyle wrestlers and students who adapted to different levels of physical activities. Under physical exertion modelling conditions, the influence of participant saliva on BLuc-Red catalyzed light emission was investigated. Results showed a significant increase in residual luminescence (Iexp , mean maximum bioluminescence intensity of the experimental measurement (Iexp ); Ic , luminescence intensity in control; Iexp /Ic , %) values for participants in the wrestler group while a decrease in the student group (P < 0.05). Such contrasting residual luminescence values in both groups were found to be dependent on the catalase activity of saliva. The proposed bioluminescence assay can be utilized as a potential nonspecific biosensing tool for determining the physical state of athletes under high loads.

Nutritional biomarkers: Current view and future perspectives.

There is a poor relationship between nutrient intake and existing nutritional biomarkers due to variety of factors affecting their sensitivity and specificity. To explore the impact of nutrients at molecular level and devising a sensitive biomarker, proteomics is a central technology with sirtuins as one of the most promising nutritional biomarker. Sirtuins (seven mammalian sirtuins reported so far) have been reported to perform protein deacetylases and ADP-ribosyltransferases activity. It is distributed in different cellular compartments thereby controlling several metabolic processes. Sirtuins are oxidized nicotinamide adenine dinucleotide dependent, which implicates a direct effect of the metabolic state of the cell on its activity. Calorie restriction upregulates the mammalian sirtuin protein levels in variety of tissues and organs where it acts upon both histone and nonhistone substrates. Sirtuin senses nutrient availability and impacts gluconeogenesis, glycolysis, and insulin sensitivity. It deacetylates and inhibits the nuclear receptor that activates fat synthesis and adipogenesis in the body, leading to fat loss and bringing favorable cellular and health changes. Sirtuins mediates intracellular response that promotes cell survival, DNA damage repair thereby increasing the cell longitivity. The activation of sirtuins brings a wide spectrum of other health benefits and its activity levels are indicative of nutritional status as well as disease progression in cancer, inflammation, obesity, cardiovascular diseases, and viral infections. There are several foods that activate sirtuin activity and offer significant health benefits by their consumption.

Status of iodine nutrition among pregnant mothers in selected districts of Uttarakhand, India.

BACKGROUND: Uttarakhand state is a known endemic area for iodine deficiency. OBJECTIVE: The present study was conducted with an objective to assess the iodine nutritional status amongst pregnant mothers (PMs) in districts: Pauri (P), Nainital (N) and Udham Singh Nagar (USN) of Uttarakhand state. MATERIALS AND METHODS: Thirty clusters from each district were selected by utilizing the population proportionate to size cluster sampling methodology. A total of 1727 PMs from P (481), N (614) and USN (632) were included. The clinical examination of the thyroid of each PM was conducted. Urine and salt samples were collected from a sub samples of PMs enlisted for thyroid clinical examination. RESULTS: The total Goiter rate was found to be 24.9 (P), 20.2 (N) and 16.1 (USN)%. The median urinary iodine concentration (UIC) levels were found to be 110 µg/L (P), 117.5 µg/L (N) and 124 µg/L (USN). The percentage of PMs consuming salt with iodine content of 15 ppm and more was found to be 57.9 (P), 67.0 (N) and 50.3 (USN). CONCLUSION: The findings of the present study revealed that the PMs in all three districts had low iodine nutritional status as revealed by UIC levels of less than 150 µg/L.

Iodine nutrition status amongst neonates in Kangra district, Himachal Pradesh.

Iodine deficiency (ID) is an endemic health problem in Kangra district, Himachal Pradesh (HP) state. ID leads to mental retardation, deaf mutism, squint, dwarfism, spastic diplegia, neurological defects and congenital anomalies. Iodine nutrition status amongst neonates can be assessed by estimating thyroid stimulating hormone (TSH). The present study was conducted with an objective to assess the iodine nutrition status amongst Neonates in Kangra district, HP. All of the hospitals in the district which provide obstetric services were enlisted, of which three were selected for this survey. A total of 613 umbilical cord blood samples of neonates were collected on filter paper and analyzed for TSH. WHO (2007) reported that that a <3% frequency of TSH concentrations above 5 mIU/L in samples collected 3-4 days after birth indicates iodine sufficiency in a population. In our study we found that 73.4% of the neonates had TSH levels of more than 5 mlU/l, thus indicating ID in the population studied. Iodine deficiency continues to be a public health problem in Kangra district, Himachal Pradesh.

Potentiation of antioxidant effect of dietary tender cluster beans (Cyamopsis tetragonoloba) by garlic (Allium sativum) in high-cholesterol-fed rats.

The antioxidant role of tender cluster beans (Cyamopsis tetragonoloba, CB), a rich source of soluble fibre, was investigated in a hypercholesterolemia-induced oxidative stress situation in rats. In the context of dietary garlic (Allium sativa) potentiating the hypocholesterolemic influence of CB, we also examined if dietary garlic enhances the antioxidant potential of CB. Groups of Wistar rats were rendered hypercholesterolemic by feeding them a 0.5% cholesterol diet for 8 weeks. Dietary interventions were made by inclusion of 15% tender CB powder or 1% garlic powder or their combination in a high-cholesterol diet. Concentrations of antioxidant molecules and activities of antioxidant enzymes in blood and liver were examined. Dietary CB displayed an antioxidant influence in terms of elevating ascorbic acid and glutathione concentrations and stimulating the activities of antioxidant enzymes both in blood and liver. The antioxidant effect of dietary CB was generally potentiated by co-administration of garlic. Thus, consumption of tender CB and garlic together could form a strategy for improving the body's antioxidant status.

Protective effect of dietary tender cluster beans (Cyamopsis tetragonoloba) in the gastrointestinal tract of experimental rats.

In this study, the gastrointestinal protective effect of soluble, dietary fiber-rich tender cluster beans, with respect to the activities of antioxidant enzymes and the concentration of antioxidant molecules, was examined in Wistar rats. Dietary intervention with tender cluster beans (15% freeze-dried powder in the diet for 8 weeks) significantly enhanced the activities of antioxidant enzymes (superoxide dismutase, catalase, glutathione reductase, glutathione-S-transferase, and GPX) and the concentrations of antioxidant molecules in both gastric and intestinal mucosa. Further, in combination with capsaicin (0.01%), the beneficial effect was even higher. There is a strong indication that tender cluster beans offer a significant gastroprotective effect, and a much greater effect when combined with capsaicin in terms of increased antioxidant status. In a separate study, these dietary components were found to alleviate the diminished activities of antioxidant enzymes and antioxidant molecules in gastric and intestinal mucosa under conditions of ethanol-induced oxidative stress. The gastroprotective effect of the cluster bean was also reflected in its positive effect on gastric mucosal glycoproteins, resulting in a lowering of mucosal injury. Incidentally, the serum and liver also showed an elevated antioxidant status, thus suggesting desirable lowered oxidative stress results when tender cluster beans are consumed.

Potentiation of hypolipidemic and weight-reducing influence of dietary tender cluster bean (Cyamopsis tetragonoloba) when combined with capsaicin in high-fat-fed rats.

Soluble fiber-rich tender cluster bean pod (Cyamopsis tetragonoloba) (CB) and a combination of CB and capsaicin, a thermogenic spice compound, were evaluated for weight-reducing effect in high-fat-fed Wistar rats. Freeze-dried CB and capsaicin were included at 15 and 0.015%, respectively, in the high-fat (30%) diet for 8 weeks. Excretion of dietary fat, fat deposition in adipose, and activities of enzymes involved in lipolysis and lipogenesis were examined. CB and capsaicin additively decreased weight gain in high-fat-fed rats, without affecting feed intake. The antiobesity potential of CB was through impeding fat accumulation in adipose and enhancing fat excretion. Decrease in adipose triglyceride by the combination was higher than their individual effects and was accompanied by enhanced activity of hormone-sensitive lipase-facilitating mobilization of depot fat. Increased fecal excretion of triglycerides by the combination of CB and capsaicin was additive. Whereas the hypolipidemic effect of the combination was higher than their individual effects, the decrease in hepatic cholesterol and triglycerides produced by the combination was additve. Thus, dietary CB significantly checked weight gain and adverse changes in lipid profile in high-fat-fed condition amounting to a cardioprotective effect. These beneficial effects were potentiated by coadministration of capsaicin.