Amar Singh - Academia.edu (original) (raw)

Papers by Amar Singh

Studies were taken up to monitor the population of sucking pests as well as boll damage in commer... more Studies were taken up to monitor the population of sucking pests as well as boll damage in commercially released Bt cotton entries. In the present study it was found that the jassid population was almost negligible (< one per three leaves) both in Bt as well as non Bt cotton hybrids. In five Bt cotton hybrids (JKCH 1947, RCH 317, NCEH 6, Ankur 2534 and MRC 6301) it was less than that of non Bt cotton hybrid. However, whitefly incidence was more in all Bt cotton hybrids than that of the non Bt cotton hybrid, which may be due to reduction in the spray of chemical insecticides or the negligible infestation of bollworms. The bollworm damage in the current experiments revealed almost nil damage to the bolls in Bt cotton compared to non Bt cotton hybrid. The seed cotton yield in 12 out of 13 Bt cotton hybrids were more than that of non Bt cotton hybrid. This reveals the superiority of Bt cotton hybrids in terms of yield.

Background and Aims. The db/þ mice, which represent the heterozygous counterpart of diabetic db/d... more Background and Aims. The db/þ mice, which represent the heterozygous counterpart of diabetic db/db mice, are carriers of the mutated gene of the leptin receptor but do not become diabetic at any stage during their lifespan. These mice are being used only for the production of db/db mice. Attempts were made to develop these mice as an alternate in vivo model for antidiabetic drug screening. Methods. Diabetes was induced by injecting streptozotocin, and establishment of diabetic condition was confirmed by measuring blood glucose level, insulin level, body weight, lipid profile, and activity of the key enzymes of carbohydrate metabolism. Results. Animals showed the characteristics of diabetes throughout the study period and also showed the beneficial effect of the treatment of the gold standard antidiabetic drug metformin that validates these mice as a screening model. Conclusions. Results showed that streptozotocin-treated db/þ mice can be used as an alternate model in antidiabetic drug discovery research. Ó 2009 IMSS. Published by Elsevier Inc.

The hybrid congeners 62−90 of 6-and 7hydroxyflavones with aminopropanol have been synthesized and... more The hybrid congeners 62−90 of 6-and 7hydroxyflavones with aminopropanol have been synthesized and evaluated for their antidiabetic activity in sucrose-challenged low-dosed streptozotocin (STZ)-induced diabetic rats and db/db mice. The optical enantiomers 70a, 70b, 90a, and 90b of two congeners 70 and 90 exhibiting consistent antidiabetic and antidyslipidemic activities were also prepared, and their antidiabetic activity results indicate its association mainly with S isomers. These compounds also lower cholesterol and TG profiles while improving high-density lipoprotein cholesterol to CHOL ratio in db/db mice. The bioavailability of compound 70 and its isomer varies between 27 and 29% whereas that of the more polar compound 90a is poor as determined in rat by oral and intraperitoneal administrations.

Diabetic cardiomyopathy (DCM) is a significant contributor to the morbidity and mortality associa... more Diabetic cardiomyopathy (DCM) is a significant contributor to the morbidity and mortality associated with diabetes and metabolic syndrome. Retinoids, through activation of retinoic acid receptor (RAR) and retinoid x receptor (RXR), have been linked to control glucose and lipid homeostasis, with effects on obesity and diabetes. However, the functional role of RAR and RXR in the development of DCM remains unclear. Zucker diabetic fatty (ZDF) and lean rats were treated with Am580 (RARα agonist) or LGD1069 (RXR agonist) for 16 weeks, and cardiac function and metabolic alterations were determined. Hyperglycemia, hyperlipidemia and insulin resistance were observed in ZDF rats. Diabetic cardiomyopathy was characterized in ZDF rats by increased oxidative stress, apoptosis, fibrosis, inflammation, activation of MAP kinases and NF-κB signaling and diminished Akt phosphorylation, along with decreased glucose transport and increased cardiac lipid accumulation, and ultimately diastolic dysfunction. Am580 and LGD1069 attenuated diabetes-induced cardiac dysfunction and the pathological alterations, by improving glucose tolerance and insulin resistance; facilitating Akt activation and glucose utilization, and attenuating oxidative stress and interrelated MAP kinase and NF-κB signaling pathways. Am580 inhibited body weight gain, attenuated the increased cardiac fatty acid uptake, β-oxidation and lipid accumulation in the hearts of ZDF rats. However, LGD1069 promoted body weight gain, hyperlipidemia and cardiac lipid accumulation. In conclusion, our data suggest that activation of RAR and RXR may have therapeutic potential in the treatment of diabetic cardiomyopathy. However, further studies are necessary to clarify the role of RAR and RXR in the regulation of lipid metabolism and homeostasis.

organism under different nutritional environments. This adaptation requires major changes in the ... more organism under different nutritional environments. This adaptation requires major changes in the hepatic metabolic gene program. One gene family, long-chain acyl-CoA synthetase (ACSL), encodes enzymes that play key roles in lipid metabolism in liver, as well as other metabolic tissues . ACSL catalyzes the formation of fatty acyl-CoA from ATP, CoA, and long-chain fatty acids (FAs). This reaction is the fi rst step in FA metabolism following transport of nonesterifi ed FA into mammalian cells. This activation process is essential for cellular utilization of FA via different metabolic pathways, including the cellular ␤ -oxidation system responsible for FA oxidation (catabolism) and the anabolic pathways for the synthesis of phospholipids, cholesterol esters, and triglycerides (TG). To date, fi ve isoforms of ACSL (ACSL1, ACSL3, ACSL4, ACSL5, and ACSL6) have been characterized in humans, mice, and rats ( 3 ). These isoforms differ considerably in their characteristics, including substrate specifi city, enzyme kinetics, and tissue and subcellular distribution. These individual characteristics contribute to their different cellular functions and metabolic outcomes ( 6-14 ). Because each isoform of the ACSL family has a distinct function in directing acyl-CoA to one or more specifi c downstream pathways, the level of expression/activity of individual ACSL isozymes could directly infl uence FA metabolic fates in liver tissue.

The article reveals the antihyperglycaemic activity of the alpha-amyrin acetate (alpha-AA) isolat... more The article reveals the antihyperglycaemic activity of the alpha-amyrin acetate (alpha-AA) isolated from the aerial roots of the Ficus bengalensis in normal and diabetic rats and model of type-2 diabetes, i.e. db/db mice. The oral administration of alpha-AA significantly improved the diabetic condition in streptozotocin-induced diabetic rats and in diabetic db/db mice at 50 mg kg(-1) dose level.

Biochimica et biophysica acta, Jan 31, 2015

a b s t r a c t The arachidonic acid preferred long-chain acyl-CoA synthetase 4 (ACSL4) is a key ... more a b s t r a c t The arachidonic acid preferred long-chain acyl-CoA synthetase 4 (ACSL4) is a key enzyme for fatty acid metabo-20 lism in various metabolic tissues. In this study, we utilized hamsters fed a normal chow diet, a high-fat diet or a 21 high cholesterol and high fat diet (HCHFD) as animal models to explore novel transcriptional regulatory mecha-22 nisms for ACSL4 expression under hyperlipidemic conditions. Through cloning hamster ACSL4 homolog and tis-23 sue profiling ACSL4 mRNA and protein expressions we observed a selective upregulation of ACSL4 in testis and 24 liver of HCHFD fed animals. Examination of transcriptional activators of the ACSL family revealed an increased he-25 patic expression of PPARδ but not PPARα in HCHFD fed hamsters. To explore a role of PPARδ in dietary 26 cholesterol-mediated upregulation of ACSL4, we administered a PPARδ specific agonist L165041 to normolipide-27 mic and dyslipidemic hamsters. We observed significant increases of hepatic ACSL4 mRNA and protein levels in 28 all L165041-treated hamsters as compared to control animals. The induction of ACSL4 expression by L165041 in 29 liver tissue in vivo was recapitulated in human primary hepatocytes and hepatocytes isolated from hamster and 30 mouse. Moreover, employing the approach of adenovirus-mediated gene knockdown, we showed that depletion 31 of PPARδ in hamster hepatocytes specifically reduced ACSL4 expression. Finally, utilizing HepG2 as a model sys-32 tem, we demonstrate that PPARδ activation leads to increased ACSL4 promoter activity, mRNA and protein ex-33 pression, and consequently higher arachidonoyl-CoA synthetase activity. Taken together, we have discovered a 34 novel PPARδ-mediated regulatory mechanism for ACSL4 expression in liver tissue and cultured hepatic cells. 35 © 2015 Published by Elsevier B.V. 36 37 38 39 40 65 of ACSL4 in rat smooth muscle cell inhibited IL-1β induced PGE2 secre-66 tion [14]. In breast cancer cells exogenous expression of ACSL4 promot-67 ed the cell invasiveness by regulating AA availability for enzymes such 68 as COX, LOX and CYP450s to generate eicosanoids [15]. In pancreatic 69 cell lines, diminished ACSL4 expression by siRNA mediated knockdown 70 reduces glucose-stimulated insulin secretion [16]. Studies also have 71 shown ACSL4 being capable of channeling fatty acid towards phos-72

Journal of experimental botany, 2015

Brassinosteroid activity controls plant growth and development, often in a seemingly opposing or ... more Brassinosteroid activity controls plant growth and development, often in a seemingly opposing or complex manner. Differential impact of the hormone and its signalling components, acting both as promoters and inhibitors of organ growth, is exemplified by meristem differentiation and cell expansion in above-and below-ground organs. Complex brassinosteroid-based control of stomata count and lateral root development has also been demonstrated. Here, mechanisms underlying these phenotypic outputs are examined. Among these, studies uncovering core brassinosteroid signalling components, which integrate with distinct peptide, hormone, and environmental pathways, are reviewed. Finally, the differential spatiotemporal context of brassinosteroid activity within the organ, as an important determinant of controlled growth, is discussed.

Atherosclerosis, Jan 30, 2015

Please cite this article as: Dong B, Singh AB, Azhar S, Seidah NG, Liu J, High-fructose feeding p... more Please cite this article as: Dong B, Singh AB, Azhar S, Seidah NG, Liu J, High-fructose feeding promotes accelerated degradation of hepatic LDL receptor and hypercholesterolemia in hamsters via elevated circulating PCSK9 levels, Atherosclerosis , PCSK9 Normal diet High furctose diet β-actin LDLR Normal diet High furctose diet Plasma Liver High fructose diet consumption led to increased circulating PCSK9 levels and reduced liver LDL receptor protein abundance in hamsters M Abstract Background: High fructose diet (HFD) induces dyslipidemia and insulin resistance in experimental animals and humans with incomplete mechanistic understanding. By utilizing mice and hamsters as in vivo models, we investigated whether high fructose consumption affects serum PCSK9 and liver LDL receptor (LDLR) protein levels.

Journal of Experimental Botany, 2009

Cysteine proteases play an important role in several developmental processes in plants, particula... more Cysteine proteases play an important role in several developmental processes in plants, particularly those related to senescence and cell death. A cysteine protease gene, RbCP1, has been identified that encodes a putative protein of 357 amino acids and is expressed in the abscission zone (AZ) of petals in rose. The gene was responsive to ethylene in petals, petal abscission zones, leaves, and thalamus. The expression of RbCP1 increased during both ethyleneinduced as well as natural abscission and was inhibited by 1-MCP. Transcript accumulation of RbCP1 was accompanied by the appearance of a 37 kDa cysteine protease, a concomitant increase in protease activity and a substantial decrease in total protein content in the AZ of petals. Agro-injection of rose petals with a 2.0 kb region upstream of the RbCP1 gene could drive GUS expression in an abscission zone-specific manner and was blocked by 1-MCP. It is concluded that petal abscission is associated with a decrease in total protein content resulting from rapid transcription of RbCP1 and the expression of a 37 kDa protease.

Injury Prevention, 2010

IntroductionDelhi government operationalised 5.8 km, phase-1 length of (14.8 km long) bus rapid t... more IntroductionDelhi government operationalised 5.8 km, phase-1 length of (14.8 km long) bus rapid transit system corridor in April 2008. First 6 months of operations witnessed six fatal accidents as against an annual average of nine during the preconstruction period; prompting this study to find reasons and measure efficacy of interventions.MethodThe corridor operator, Delhi Integrated Multi-Modal Transit System, introduced monitoring processes,

Studies were taken up to monitor the population of sucking pests as well as boll damage in commer... more Studies were taken up to monitor the population of sucking pests as well as boll damage in commercially released Bt cotton entries. In the present study it was found that the jassid population was almost negligible (< one per three leaves) both in Bt as well as non Bt cotton hybrids. In five Bt cotton hybrids (JKCH 1947, RCH 317, NCEH 6, Ankur 2534 and MRC 6301) it was less than that of non Bt cotton hybrid. However, whitefly incidence was more in all Bt cotton hybrids than that of the non Bt cotton hybrid, which may be due to reduction in the spray of chemical insecticides or the negligible infestation of bollworms. The bollworm damage in the current experiments revealed almost nil damage to the bolls in Bt cotton compared to non Bt cotton hybrid. The seed cotton yield in 12 out of 13 Bt cotton hybrids were more than that of non Bt cotton hybrid. This reveals the superiority of Bt cotton hybrids in terms of yield.

Background and Aims. The db/þ mice, which represent the heterozygous counterpart of diabetic db/d... more Background and Aims. The db/þ mice, which represent the heterozygous counterpart of diabetic db/db mice, are carriers of the mutated gene of the leptin receptor but do not become diabetic at any stage during their lifespan. These mice are being used only for the production of db/db mice. Attempts were made to develop these mice as an alternate in vivo model for antidiabetic drug screening. Methods. Diabetes was induced by injecting streptozotocin, and establishment of diabetic condition was confirmed by measuring blood glucose level, insulin level, body weight, lipid profile, and activity of the key enzymes of carbohydrate metabolism. Results. Animals showed the characteristics of diabetes throughout the study period and also showed the beneficial effect of the treatment of the gold standard antidiabetic drug metformin that validates these mice as a screening model. Conclusions. Results showed that streptozotocin-treated db/þ mice can be used as an alternate model in antidiabetic drug discovery research. Ó 2009 IMSS. Published by Elsevier Inc.

The hybrid congeners 62−90 of 6-and 7hydroxyflavones with aminopropanol have been synthesized and... more The hybrid congeners 62−90 of 6-and 7hydroxyflavones with aminopropanol have been synthesized and evaluated for their antidiabetic activity in sucrose-challenged low-dosed streptozotocin (STZ)-induced diabetic rats and db/db mice. The optical enantiomers 70a, 70b, 90a, and 90b of two congeners 70 and 90 exhibiting consistent antidiabetic and antidyslipidemic activities were also prepared, and their antidiabetic activity results indicate its association mainly with S isomers. These compounds also lower cholesterol and TG profiles while improving high-density lipoprotein cholesterol to CHOL ratio in db/db mice. The bioavailability of compound 70 and its isomer varies between 27 and 29% whereas that of the more polar compound 90a is poor as determined in rat by oral and intraperitoneal administrations.

Diabetic cardiomyopathy (DCM) is a significant contributor to the morbidity and mortality associa... more Diabetic cardiomyopathy (DCM) is a significant contributor to the morbidity and mortality associated with diabetes and metabolic syndrome. Retinoids, through activation of retinoic acid receptor (RAR) and retinoid x receptor (RXR), have been linked to control glucose and lipid homeostasis, with effects on obesity and diabetes. However, the functional role of RAR and RXR in the development of DCM remains unclear. Zucker diabetic fatty (ZDF) and lean rats were treated with Am580 (RARα agonist) or LGD1069 (RXR agonist) for 16 weeks, and cardiac function and metabolic alterations were determined. Hyperglycemia, hyperlipidemia and insulin resistance were observed in ZDF rats. Diabetic cardiomyopathy was characterized in ZDF rats by increased oxidative stress, apoptosis, fibrosis, inflammation, activation of MAP kinases and NF-κB signaling and diminished Akt phosphorylation, along with decreased glucose transport and increased cardiac lipid accumulation, and ultimately diastolic dysfunction. Am580 and LGD1069 attenuated diabetes-induced cardiac dysfunction and the pathological alterations, by improving glucose tolerance and insulin resistance; facilitating Akt activation and glucose utilization, and attenuating oxidative stress and interrelated MAP kinase and NF-κB signaling pathways. Am580 inhibited body weight gain, attenuated the increased cardiac fatty acid uptake, β-oxidation and lipid accumulation in the hearts of ZDF rats. However, LGD1069 promoted body weight gain, hyperlipidemia and cardiac lipid accumulation. In conclusion, our data suggest that activation of RAR and RXR may have therapeutic potential in the treatment of diabetic cardiomyopathy. However, further studies are necessary to clarify the role of RAR and RXR in the regulation of lipid metabolism and homeostasis.

organism under different nutritional environments. This adaptation requires major changes in the ... more organism under different nutritional environments. This adaptation requires major changes in the hepatic metabolic gene program. One gene family, long-chain acyl-CoA synthetase (ACSL), encodes enzymes that play key roles in lipid metabolism in liver, as well as other metabolic tissues . ACSL catalyzes the formation of fatty acyl-CoA from ATP, CoA, and long-chain fatty acids (FAs). This reaction is the fi rst step in FA metabolism following transport of nonesterifi ed FA into mammalian cells. This activation process is essential for cellular utilization of FA via different metabolic pathways, including the cellular ␤ -oxidation system responsible for FA oxidation (catabolism) and the anabolic pathways for the synthesis of phospholipids, cholesterol esters, and triglycerides (TG). To date, fi ve isoforms of ACSL (ACSL1, ACSL3, ACSL4, ACSL5, and ACSL6) have been characterized in humans, mice, and rats ( 3 ). These isoforms differ considerably in their characteristics, including substrate specifi city, enzyme kinetics, and tissue and subcellular distribution. These individual characteristics contribute to their different cellular functions and metabolic outcomes ( 6-14 ). Because each isoform of the ACSL family has a distinct function in directing acyl-CoA to one or more specifi c downstream pathways, the level of expression/activity of individual ACSL isozymes could directly infl uence FA metabolic fates in liver tissue.

The article reveals the antihyperglycaemic activity of the alpha-amyrin acetate (alpha-AA) isolat... more The article reveals the antihyperglycaemic activity of the alpha-amyrin acetate (alpha-AA) isolated from the aerial roots of the Ficus bengalensis in normal and diabetic rats and model of type-2 diabetes, i.e. db/db mice. The oral administration of alpha-AA significantly improved the diabetic condition in streptozotocin-induced diabetic rats and in diabetic db/db mice at 50 mg kg(-1) dose level.

Biochimica et biophysica acta, Jan 31, 2015

a b s t r a c t The arachidonic acid preferred long-chain acyl-CoA synthetase 4 (ACSL4) is a key ... more a b s t r a c t The arachidonic acid preferred long-chain acyl-CoA synthetase 4 (ACSL4) is a key enzyme for fatty acid metabo-20 lism in various metabolic tissues. In this study, we utilized hamsters fed a normal chow diet, a high-fat diet or a 21 high cholesterol and high fat diet (HCHFD) as animal models to explore novel transcriptional regulatory mecha-22 nisms for ACSL4 expression under hyperlipidemic conditions. Through cloning hamster ACSL4 homolog and tis-23 sue profiling ACSL4 mRNA and protein expressions we observed a selective upregulation of ACSL4 in testis and 24 liver of HCHFD fed animals. Examination of transcriptional activators of the ACSL family revealed an increased he-25 patic expression of PPARδ but not PPARα in HCHFD fed hamsters. To explore a role of PPARδ in dietary 26 cholesterol-mediated upregulation of ACSL4, we administered a PPARδ specific agonist L165041 to normolipide-27 mic and dyslipidemic hamsters. We observed significant increases of hepatic ACSL4 mRNA and protein levels in 28 all L165041-treated hamsters as compared to control animals. The induction of ACSL4 expression by L165041 in 29 liver tissue in vivo was recapitulated in human primary hepatocytes and hepatocytes isolated from hamster and 30 mouse. Moreover, employing the approach of adenovirus-mediated gene knockdown, we showed that depletion 31 of PPARδ in hamster hepatocytes specifically reduced ACSL4 expression. Finally, utilizing HepG2 as a model sys-32 tem, we demonstrate that PPARδ activation leads to increased ACSL4 promoter activity, mRNA and protein ex-33 pression, and consequently higher arachidonoyl-CoA synthetase activity. Taken together, we have discovered a 34 novel PPARδ-mediated regulatory mechanism for ACSL4 expression in liver tissue and cultured hepatic cells. 35 © 2015 Published by Elsevier B.V. 36 37 38 39 40 65 of ACSL4 in rat smooth muscle cell inhibited IL-1β induced PGE2 secre-66 tion [14]. In breast cancer cells exogenous expression of ACSL4 promot-67 ed the cell invasiveness by regulating AA availability for enzymes such 68 as COX, LOX and CYP450s to generate eicosanoids [15]. In pancreatic 69 cell lines, diminished ACSL4 expression by siRNA mediated knockdown 70 reduces glucose-stimulated insulin secretion [16]. Studies also have 71 shown ACSL4 being capable of channeling fatty acid towards phos-72

Journal of experimental botany, 2015

Brassinosteroid activity controls plant growth and development, often in a seemingly opposing or ... more Brassinosteroid activity controls plant growth and development, often in a seemingly opposing or complex manner. Differential impact of the hormone and its signalling components, acting both as promoters and inhibitors of organ growth, is exemplified by meristem differentiation and cell expansion in above-and below-ground organs. Complex brassinosteroid-based control of stomata count and lateral root development has also been demonstrated. Here, mechanisms underlying these phenotypic outputs are examined. Among these, studies uncovering core brassinosteroid signalling components, which integrate with distinct peptide, hormone, and environmental pathways, are reviewed. Finally, the differential spatiotemporal context of brassinosteroid activity within the organ, as an important determinant of controlled growth, is discussed.

Atherosclerosis, Jan 30, 2015

Please cite this article as: Dong B, Singh AB, Azhar S, Seidah NG, Liu J, High-fructose feeding p... more Please cite this article as: Dong B, Singh AB, Azhar S, Seidah NG, Liu J, High-fructose feeding promotes accelerated degradation of hepatic LDL receptor and hypercholesterolemia in hamsters via elevated circulating PCSK9 levels, Atherosclerosis , PCSK9 Normal diet High furctose diet β-actin LDLR Normal diet High furctose diet Plasma Liver High fructose diet consumption led to increased circulating PCSK9 levels and reduced liver LDL receptor protein abundance in hamsters M Abstract Background: High fructose diet (HFD) induces dyslipidemia and insulin resistance in experimental animals and humans with incomplete mechanistic understanding. By utilizing mice and hamsters as in vivo models, we investigated whether high fructose consumption affects serum PCSK9 and liver LDL receptor (LDLR) protein levels.

Journal of Experimental Botany, 2009

Cysteine proteases play an important role in several developmental processes in plants, particula... more Cysteine proteases play an important role in several developmental processes in plants, particularly those related to senescence and cell death. A cysteine protease gene, RbCP1, has been identified that encodes a putative protein of 357 amino acids and is expressed in the abscission zone (AZ) of petals in rose. The gene was responsive to ethylene in petals, petal abscission zones, leaves, and thalamus. The expression of RbCP1 increased during both ethyleneinduced as well as natural abscission and was inhibited by 1-MCP. Transcript accumulation of RbCP1 was accompanied by the appearance of a 37 kDa cysteine protease, a concomitant increase in protease activity and a substantial decrease in total protein content in the AZ of petals. Agro-injection of rose petals with a 2.0 kb region upstream of the RbCP1 gene could drive GUS expression in an abscission zone-specific manner and was blocked by 1-MCP. It is concluded that petal abscission is associated with a decrease in total protein content resulting from rapid transcription of RbCP1 and the expression of a 37 kDa protease.

Injury Prevention, 2010

IntroductionDelhi government operationalised 5.8 km, phase-1 length of (14.8 km long) bus rapid t... more IntroductionDelhi government operationalised 5.8 km, phase-1 length of (14.8 km long) bus rapid transit system corridor in April 2008. First 6 months of operations witnessed six fatal accidents as against an annual average of nine during the preconstruction period; prompting this study to find reasons and measure efficacy of interventions.MethodThe corridor operator, Delhi Integrated Multi-Modal Transit System, introduced monitoring processes,