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Bioessays
2014 Jan 01;361:27-33. doi: 10.1002/bies.201300110.
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Carbohydrate metabolism during vertebrate appendage regeneration: what is its role? How is it regulated?: A postulation that regenerating vertebrate appendages facilitate glycolytic and pentose phosphate pathways to fuel macromolecule biosynthesis.
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We recently examined gene expression during Xenopus tadpoletailappendage regeneration and found that carbohydrate regulatory genes were dramatically altered during the regeneration process. In this essay, we speculate that these changes in gene expression play an essential role during regeneration by stimulating the anabolic pathways required for the reconstruction of a new appendage. We hypothesize that during regeneration, cells use leptin, slc2a3, proinsulin, g6pd, hif1α expression, receptor tyrosine kinase (RTK) signaling, and the production of reactive oxygen species (ROS) to promote glucose entry into glycolysis and the pentose phosphate pathway (PPP), thus stimulating macromolecular biosynthesis. We suggest that this metabolic shift is integral to the appendage regeneration program and that the Xenopus model is a powerful experimental system to further explore this phenomenon. Also watch the Video Abstract.
Figure 1. Tissue regrowth during Xenopus tadpoletailappendage regeneration. A: Xenopus laevis tadpole. Scale bar represents 500 µm. B: Schematic diagram of a transverse section of the tadpoletail. C: Transillumination and fluorescence images showing the recruitment of inflammatory cells to the amputation site by 3 hours post-amputation (hpa). Blue arrow shows blood and other cellular debris that spilled from the wound site by 1 minute post-amputation (mpa). Fluorescence signal detects inflammatory cells using a Xenopus laevis transgenic line 42. Scale bar represents 500 µm and is applicable to the panels in D and E. D: Transillumination and immunofluorescence (anti-phosphohistone H3) images showing proliferating cells at two different time periods during Xenopus laevis tail regeneration. Open red arrow shows regenerative bud tissue. E: Transillumination and immunofluorescence images showing the regeneration of neuronal tissue (anti-N-acetylated tubulin), vascular tissue (Flk-1: eGFP X. laevis transgenic line 45, and skeletal muscle (anti-12/101, 46).
Figure 2. Production of biosynthetic precursors during glycolytic metabolism and their putative regulation during Xenopus tailappendage regeneration. A: Pathways demonstrating how glucose or its derivatives can contribute to biosynthetic processes as well as how glucose metabolism may be regulated during appendage regeneration as outlined in the essay. Diagram adapted from 13,16,24. Colors indicate conceptually different pathways or interactions: glycolysis toward glucose combustion (black); pentose phosphate pathway (PPP, shown in red); molecular contributions of biosynthetic pathways (blue); NAD/H, NADP/H, ATD/P reactions shown in green; reintroduction of PPP products into glycolysis (gray); putative inhibitory mechanisms during Xenopus tadpoletail regeneration (yellow); putative activation mechanisms during Xenopus tadpoletail regeneration (purple); putative activity of PI3/Akt given its previously characterized interactions with leptin/insulin/RTK activity 9,15. Asterisk (*) indicates that the PK inhibition by ROS and tyrosine kinase activity have been reported for the PKM2 version of the PK enzyme 19,20. Acronyms are as follows: HK, hexokinase; G6PD, glucose-6-phosphate dehydrogenase; 6PGL, 6-phosphogluconolactonase; 6PGDH, 6-phosphogluconate dehydrogenase; PPEI, phosphopentoseisomerase; PPE, phosphopentose epimerase; PFK, phosphofructokinase; TK, transketolase; TA, transaldolase; PGI, phosphoglucose isomerase; ALDO, aldolase; TPI, triosephosphate isomerase; GAPDH, glyceraldehyde phosphate dehydrogenase; PGK, phosphoglycerate kinase; PGAM, phosphoglycerate mutase; ENO, enolase; PK, pyruvate kinase. B: In situ hybridization showing expression of g6pd following amputation and during the regeneration of Xenopus tropicalis tadpole tails. Solid red arrow shows a portion of the notochord that has exited the wound site. Open red arrow shows regenerative bud tissue. C: Transillumination (trans) and HyperYFP ([H2O2]) images showing the detection of the reactive oxygen species (ROS) hydrogen peroxide (H2O2) following Xenopus laevis tail amputation using the H2O2 sensitive HyPerYFP probe 21,42. Relative levels of H2O2 levels shown in the scale found to the right of the images. Solid red arrow shows a portion of the notochord that has exited the wound site.
Agathocleous,
Metabolic differentiation in the embryonic retina.
2012, Pubmed,
Xenbase
Agathocleous,
Metabolic differentiation in the embryonic retina.
2012,
Pubmed
,
Xenbase
Agathocleous,
Metabolism in physiological cell proliferation and differentiation.
2013,
Pubmed
Altenberg,
Genes of glycolysis are ubiquitously overexpressed in 24 cancer classes.
2004,
Pubmed
Amaya,
Xenomics.
2005,
Pubmed
,
Xenbase
Anastasiou,
Inhibition of pyruvate kinase M2 by reactive oxygen species contributes to cellular antioxidant responses.
2011,
Pubmed
Beck,
Beyond early development: Xenopus as an emerging model for the study of regenerative mechanisms.
2009,
Pubmed
,
Xenbase
Beck,
Molecular pathways needed for regeneration of spinal cord and muscle in a vertebrate.
2003,
Pubmed
,
Xenbase
Belousov,
Genetically encoded fluorescent indicator for intracellular hydrogen peroxide.
2006,
Pubmed
Brockes,
Comparative aspects of animal regeneration.
2008,
Pubmed
Ceddia,
Comparing effects of leptin and insulin on glucose metabolism in skeletal muscle: evidence for an effect of leptin on glucose uptake and decarboxylation.
1999,
Pubmed
Chiarugi,
The NAD metabolome--a key determinant of cancer cell biology.
2012,
Pubmed
Christofk,
The M2 splice isoform of pyruvate kinase is important for cancer metabolism and tumour growth.
2008,
Pubmed
Curtin,
Enzymic retrodifferentiation during hepatocarcinogenesis and liver regeneration in rats in vivo.
1983,
Pubmed
DeBerardinis,
The biology of cancer: metabolic reprogramming fuels cell growth and proliferation.
2008,
Pubmed
DeNicola,
Oncogene-induced Nrf2 transcription promotes ROS detoxification and tumorigenesis.
2011,
Pubmed
Denko,
Hypoxia, HIF1 and glucose metabolism in the solid tumour.
2008,
Pubmed
Doherty,
A flk-1 promoter/enhancer reporter transgenic Xenopus laevis generated using the Sleeping Beauty transposon system: an in vivo model for vascular studies.
2007,
Pubmed
,
Xenbase
Gambhir,
Molecular imaging of cancer with positron emission tomography.
2002,
Pubmed
Gargioli,
Cell lineage tracing during Xenopus tail regeneration.
2004,
Pubmed
,
Xenbase
Gilchrist,
Defining a large set of full-length clones from a Xenopus tropicalis EST project.
2004,
Pubmed
,
Xenbase
Hamanaka,
Targeting glucose metabolism for cancer therapy.
2012,
Pubmed
Hellsten,
The genome of the Western clawed frog Xenopus tropicalis.
2010,
Pubmed
,
Xenbase
Hitosugi,
Tyrosine phosphorylation inhibits PKM2 to promote the Warburg effect and tumor growth.
2009,
Pubmed
Ho,
TGF-beta signaling is required for multiple processes during Xenopus tail regeneration.
2008,
Pubmed
,
Xenbase
Hung,
Imaging cytosolic NADH-NAD(+) redox state with a genetically encoded fluorescent biosensor.
2011,
Pubmed
Ishibashi,
Highly efficient bi-allelic mutation rates using TALENs in Xenopus tropicalis.
2012,
Pubmed
,
Xenbase
Kintner,
Monoclonal antibodies identify blastemal cells derived from dedifferentiating limb regeneration.
,
Pubmed
,
Xenbase
Koppenol,
Otto Warburg's contributions to current concepts of cancer metabolism.
2011,
Pubmed
Krisher,
A role for the Warburg effect in preimplantation embryo development: metabolic modification to support rapid cell proliferation.
2012,
Pubmed
Lin,
Requirement for Wnt and FGF signaling in Xenopus tadpole tail regeneration.
2008,
Pubmed
,
Xenbase
Liu,
Targeting the phosphoinositide 3-kinase pathway in cancer.
2009,
Pubmed
Love,
Genome-wide analysis of gene expression during Xenopus tropicalis tadpole tail regeneration.
2011,
Pubmed
,
Xenbase
Love,
pTransgenesis: a cross-species, modular transgenesis resource.
2011,
Pubmed
,
Xenbase
Love,
Amputation-induced reactive oxygen species are required for successful Xenopus tadpole tail regeneration.
2013,
Pubmed
,
Xenbase
Morris,
Recent advances in understanding leptin signaling and leptin resistance.
2009,
Pubmed
Panopoulos,
The metabolome of induced pluripotent stem cells reveals metabolic changes occurring in somatic cell reprogramming.
2012,
Pubmed
Redel,
Glycolysis in preimplantation development is partially controlled by the Warburg Effect.
2012,
Pubmed
Roos,
Changes in the carbohydrate metabolism of mitogenically stimulated human peripheral lymphocytes. II. Relative importance of glycolysis and oxidative phosphorylation on phytohaemagglutinin stimulation.
1973,
Pubmed
Sánchez Alvarado,
Bridging the regeneration gap: genetic insights from diverse animal models.
2006,
Pubmed
Shyh-Chang,
Stem cell metabolism in tissue development and aging.
2013,
Pubmed
Sierra-Honigmann,
Biological action of leptin as an angiogenic factor.
1998,
Pubmed
Suh,
Cell transformation by the superoxide-generating oxidase Mox1.
1999,
Pubmed
Thorens,
Glucose transporters in the 21st Century.
2010,
Pubmed
Tian,
Importance of glucose-6-phosphate dehydrogenase activity for cell growth.
1998,
Pubmed
Vander Heiden,
Understanding the Warburg effect: the metabolic requirements of cell proliferation.
2009,
Pubmed
