XB-ART-47652Bioessays January 1, 2014; 36 (1): 27-33.
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.
We recently examined gene expression during Xenopus tadpole tail appendage 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.
PubMed ID: 24264888
PMC ID: PMC3992846
Article link: Bioessays
Species referenced: Xenopus
Genes referenced: akt1 bgn g6pd hpse kdr lep pfkm prkg1 slc2a3 tkt tpi1 ubl4a
Article Images: [+] show captions
|Figure 1. Tissue regrowth during Xenopus tadpole tail appendage regeneration. A: Xenopus laevis tadpole. Scale bar represents 500 µm. B: Schematic diagram of a transverse section of the tadpole tail. 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 tail appendage 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 tadpole tail regeneration (yellow); putative activation mechanisms during Xenopus tadpole tail 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.|
References [+] :
Agathocleous, Metabolism in physiological cell proliferation and differentiation. 2013, Pubmed