Aldose metabolism in developing human fetal brain and liver

Samanta, Bimal; Chandra, Naresh; Mukherjee, Krishnendu

doi:10.1007/bf01951922

Cited by 7 publications

(5 citation statements)

References 16 publications

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“…However, these data are inconsistent with data showing that sheep placenta expresses high levels of aldose reductase, but not sorbitol dehydrogenase [ 31 , 32 ]. Regardless, given that sorbitol dehydrogenase is known to be present in human fetal liver and brain [ 33 ], our findings raise the intriguing possibility that the sorbitol generated by the placenta could still be a substrate for fetal fructose production, which may have important ramifications for the developing fetal brain. Furthermore, because our samples were collected in the absence of labor, they may be a more accurate reflection of fetal exposure as it has been shown that stress from labor induces higher cord blood levels of glucose and fructose compared to levels obtained in the absence of labor [ 34 ].…”

Section: Discussionmentioning

confidence: 86%

Fructose Levels Are Markedly Elevated in Cerebrospinal Fluid Compared to Plasma in Pregnant Women

et al. 2015

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BackgroundFructose, unlike glucose, promotes feeding behavior in rodents and its ingestion exerts differential effects in the human brain. However, plasma fructose is typically 1/1000th of glucose levels and it is unclear to what extent fructose crosses the blood-brain barrier. We investigated whether local endogenous central nervous system (CNS) fructose production from glucose via the polyol pathway (glucose→sorbitol→fructose) contributes to brain exposure to fructose.MethodsIn this observational study, fasting glucose, sorbitol and fructose concentrations were measured using gas-chromatography-liquid mass spectroscopy in cerebrospinal fluid (CSF), maternal plasma, and venous cord blood collected from 25 pregnant women (6 lean, 10 overweight/obese, and 9 T2DM/gestational DM) undergoing spinal anesthesia and elective cesarean section.ResultsAs expected, CSF glucose was ~60% of plasma glucose levels. In contrast, fructose was nearly 20-fold higher in CSF than in plasma (p < 0.001), and CSF sorbitol was ~9-times higher than plasma levels (p < 0.001). Moreover, CSF fructose correlated positively with CSF glucose (ρ 0.45, p = 0.02) and sorbitol levels (ρ 0.75, p < 0.001). Cord blood sorbitol was also ~7-fold higher than maternal plasma sorbitol levels (p = 0.001). There were no differences in plasma, CSF, and cord blood glucose, fructose, or sorbitol levels between groups.ConclusionsThese data raise the possibility that fructose may be produced endogenously in the human brain and that the effects of fructose in the human brain and placenta may extend beyond its dietary consumption.

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Section: Discussionmentioning

confidence: 86%

Fructose Levels Are Markedly Elevated in Cerebrospinal Fluid Compared to Plasma in Pregnant Women

et al. 2015

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“…During embryonic development AR plays an important role in the liver to reduce carbohydrates. Increased expression of AR in the fetal liver up to 16 th week of gestation and disappearance at later stages suggests that in normal adult liver AR is not required [82]. However, AR is reexpressed with functionally active enzyme in response to the loss or reduction of activity of various glycolytic enzymes and increased proliferative activity during hepatocarcinogenesis [83].…”

Section: Role Of Ar In Carcinogenesismentioning

confidence: 99%

Targeting Aldose Reductase for the Treatment of Cancer

Tammali

Srivastava²,

Ramana³

2011

CCDT

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It is strongly established by numerous studies that oxidative stress-induced inflammation is one of the major causative agents in a variety of cancers. Various factors such as bacterial, viral, parasitic infections, chemical irritants, carcinogens are involved in the initiation of oxidative stress-mediated inflammation. Chronic and persistent inflammation promotes the formation of cancerous tumors. Recent investigations strongly suggest that aldose reductase [AR; AKR1B1], a member of aldo-keto reductase superfamily of proteins, is the mediator of inflammatory signals induced by growth factors, cytokines, chemokines, carcinogens etc. Further, AR reduced product(s) of lipid derived aldehydes and their metabolites such as glutathionyl 1,4-dihydroxynonanol (GS-DHN) have been shown to be involved in the activation of transcription factors such as NF-κB and AP-1 which transcribe the genes of inflammatory cytokines. The increased inflammatory cytokines and growth factors promote cell proliferation, a main feature involved in the tumorigenesis process. Inhibition of AR has been shown to prevent cancer cell growth in vitro and in vivo models. In this review, we have described the possible association between AR with oxidative stress- and inflammation- initiated carcinogenesis. A thorough understanding of the role of AR in the inflammation – associated cancers could lead to the use of AR inhibitors as novel chemotherapeutic agents against cancer.

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“…In the liver, AR was found to be transiently expressed during embryogenesis [ 3 ]. In adult animals, hepatic AR expression or activity is barely detectable or absent [ 3 , 4 ].…”

Section: Introductionmentioning

confidence: 99%

“…In the liver, AR was found to be transiently expressed during embryogenesis [ 3 ]. In adult animals, hepatic AR expression or activity is barely detectable or absent [ 3 , 4 ]. A number of recent studies, nonetheless, have shown that hepatic AR can be significantly induced and activated under a variety of stress conditions or in diseased livers.…”

Section: Introductionmentioning

confidence: 99%

Aldose reductase interacts with AKT1 to augment hepatic AKT/mTOR signaling and promote hepatocarcinogenesis

et al. 2017

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Marked up-regulation of aldose reductase (AR) is reportedly associated with the development of hepatocellular carcinoma (HCC). We investigated how aberrantly overexpressed AR might promote oncogenic transformation in liver cells and tissues. We found that overexpressed AR interacted with the kinase domain of AKT1 to increase AKT/mTOR signaling. In both cultured liver cancer cells and liver tissues in DEN-induced transgenic HCC model mice, we observed that AR overexpression-induced AKT/mTOR signaling tended to enhance lactate formation and hepatic inflammation to enhance hepatocarcinogenesis. Conversely, AR knockdown suppressed lactate formation and inflammation. Using cultured liver cancer cells, we also demonstrated that AKT1 was essential for AR-induced dysregulation of AKT/mTOR signaling, metabolic reprogramming, antioxidant defense, and inflammatory responses. These findings suggest that aberrantly overexpressed/over-activated hepatic AR promotes HCC development at least in part by interacting with oncogenic AKT1 to augment AKT/mTOR signaling. Inhibition of AR and/or AKT1 might serve as an effective strategy for the prevention and therapy of liver cancer.

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Aldose metabolism in developing human fetal brain and liver

Cited by 7 publications

References 16 publications

Fructose Levels Are Markedly Elevated in Cerebrospinal Fluid Compared to Plasma in Pregnant Women

Fructose Levels Are Markedly Elevated in Cerebrospinal Fluid Compared to Plasma in Pregnant Women

Targeting Aldose Reductase for the Treatment of Cancer

Aldose reductase interacts with AKT1 to augment hepatic AKT/mTOR signaling and promote hepatocarcinogenesis

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