Dehydrogenases and aldolase in the regenerating forelimb of the adult newt, <i>Diemictylus viridescens</i>

Schmidt, Anthony J.; Weidman, Thomas A.

doi:10.1002/jez.1401550304

Cited by 30 publications

(4 citation statements)

References 28 publications

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“…In general, prior to the formation of a blastema, lysosomal enzymes are thought to be required in the dedifferentiating tissues of the stump to catalyze the breakdown of proteins and extracellular matrix. Collagenase and several acid hydrolases have been detected in the limb blastema of the newt, Notophthalmus uiridescens (Schmidt and Weidman, 1964;Grill0 et al, 1968). Acid phosphatase belongs to the group of acid hydrolases which characterizes the lysosome in several types of vertebrate tissue and has been widely accepted as a primary marker of lysosomal activity.…”

Section: Effects Of Ra On Acid Phosphatase Activitymentioning

confidence: 99%

Pattern duplication by retinoic acid treatment in the regenerating limbs of Korean salamander larvae, Hynobius leechii, correlates well with the extent of dedifferentiation

Kim

1994

Developmental Dynamics

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In the regenerating limbs of Korean salamanders, Hynobius leechii, retinoic acid (RA) induces duplication of skeletal structures in the proximodistal (PD) axis and often in the transverse axes. In the present study, the stage-dependent effects of RA for the duplication of limb skeletal structures at two amputation levels, the distal stylopodium and the distal zeugopodium, were studied using larval limbs of Korean salamanders. The results showed that the mean level of proximalization (MLP) by RA treatment increased during the stages of dedifferentiation and early bud formation while the MLP declined thereafter in both amputation levels. The decline of the MLP at the later stages of regeneration was due to the high frequency of hypomorphic regeneration or blocked regeneration. When the effects of RA treatment at two amputation levels were compared, the overall trends were similar but the actual timing was delayed for 2-4 days in the proximal level of amputation. Furthermore, the peak level of proximalization was achieved earlier and the peak level remained longer in the distal stylopodial level of amputation compared to the distal zeugopodial level of amputation. Since the histological observations revealed that the dedifferentiation period was also extended up to 2-4 days in the proximal level of amputation, the acid phosphatase activity during the course of regeneration was measured to look for a quantitative relationship between the enzyme activity and the states of dedifferentiation. The results show that the level and the duration of acid phosphatase activity in the upper arm regenerates are both higher and longer than those in the lower arm regenerates. Furthermore, RA treatment caused an increase in acid phosphatase activity. Thus our results suggest that the state of dedifferentiation might be closely linked to the extent of proximalization of regenerating limbs by RA treatment.

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Section: Effects Of Ra On Acid Phosphatase Activitymentioning

confidence: 99%

Pattern duplication by retinoic acid treatment in the regenerating limbs of Korean salamander larvae, Hynobius leechii, correlates well with the extent of dedifferentiation

Kim

1994

Developmental Dynamics

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“…In this sense, certain histochemical studies during forelimb regeneration of the newt Notophthalmus viridescens, showed blastemal cells with a constant low response of the in situ enzymatic activity for succinate dehydrogenase and isocitrate dehydrogenase (Wolfe and Cohen, 1963;Johnson and Singer, 1964;Schmidt and Weidman, 1964). Likewise, it has been reported in the regeneration blastema high levels of lactic acid with a low respiratory quotient, as well as an increased glucose-6-phosphate dehydrogenase activity, suggesting a significant change in the metabolism of blastemal cells aimed at partially replacing the Krebs cycle by a glycolytic activity and/or the pentose phosphate pathway (Wolfe and Cohen, 1963;Johnson and Singer, 1964;Schmidt and Weidman, 1964). The induced overexpression of Lin28A in mouse neonatal tissues, it has also been shown that improves regeneration by a rewiring of the primary energetic metabolism, where the glycolysis is favored to increase intermediary metabolites of the Krebs cycle (Shyh-Chang et al, 2013).…”

Section: Introductionmentioning

confidence: 98%

“…Therefore, an adequate cell metabolic state is relevant for regeneration, since the AKT-mTOR pathway acts as an important mediator between anabolic and catabolic cell reactions (Altomare and Khaled, 2012;Saxton and Sabatini, 2017). In this sense, certain histochemical studies during forelimb regeneration of the newt Notophthalmus viridescens, showed blastemal cells with a constant low response of the in situ enzymatic activity for succinate dehydrogenase and isocitrate dehydrogenase (Wolfe and Cohen, 1963;Johnson and Singer, 1964;Schmidt and Weidman, 1964). Likewise, it has been reported in the regeneration blastema high levels of lactic acid with a low respiratory quotient, as well as an increased glucose-6-phosphate dehydrogenase activity, suggesting a significant change in the metabolism of blastemal cells aimed at partially replacing the Krebs cycle by a glycolytic activity and/or the pentose phosphate pathway (Wolfe and Cohen, 1963;Johnson and Singer, 1964;Schmidt and Weidman, 1964).…”

Section: Introductionmentioning

confidence: 99%

Functional Characterization of the Lin28/let-7 Circuit During Forelimb Regeneration in Ambystoma mexicanum and Its Influence on Metabolic Reprogramming

Varela-Rodríguez

Abella-Quintana

Espinal-Centeno

et al. 2020

Front. Cell Dev. Biol.

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The axolotl (Ambystoma mexicanum) is a caudate amphibian, which has an extraordinary ability to restore a wide variety of damaged structures by a process denominated epimorphosis. While the origin and potentiality of progenitor cells that take part during epimorphic regeneration are known to some extent, the metabolic changes experienced and their associated implications, remain unexplored. However, a circuit with a potential role as a modulator of cellular metabolism along regeneration is that formed by Lin28/let-7. In this study, we report two Lin28 paralogs and eight mature let-7 microRNAs encoded in the axolotl genome. Particularly, in the proliferative blastema stage amxLin28B is more abundant in the nuclei of blastemal cells, while the microRNAs amx-let-7c and amx-let-7a are most downregulated. Functional inhibition of Lin28 factors increase the levels of most mature let-7 microRNAs, consistent with an increment of intermediary metabolites of the Krebs cycle, and phenotypic alterations in the outgrowth of the blastema. In summary, we describe the primary components of the Lin28/let-7 circuit and their function during axolotl regeneration, acting upstream of metabolic reprogramming events.

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“…Among the newly synthesized proteins some of them are certainly remodeling enzymes of the stump tissues. In fact, various lysosomal acid hydrolases such as acid phosphatase, cathepsins, carboxylic ester hydrolase, and 0-glucuronidase had been found in the dedifferentiating limbs of urodele (Dukiet and Niwelinski, 1960;Schmidt and Weidman, 1964;Schmidt and Norman, 1965;Slattery and Schmidt, 1975;Kim, 1994, 1998). Also, serine proteases (trypsin-and chymotrypsin-like enzymes) have been found to increase in the regenerating salamander limb (Lee and Kim, 1996), and the activities of MMPs (matrix metalloproteinases) and collagenases have also been noted to increase in the regenerating limbs of urodele (Grillo et al, 1968;Park and Kim, 1999) during dedifferentiation.…”

Section: Discussionmentioning

confidence: 99%

Protein synthesis pattern analysis in the regenerating salamander limb

Kim

2000

Korean Journal of Biological Sciences

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Retinoic acid (RA) evokes pattern duplication in the regenerating salamander limb. Interestingly, it also enhances dedifferentiation in the regenerate by the morphological, histological and biochemical criteria. To examine whether there is any correlation between the RA-evoked pattern duplication and de novo protein synthetic profile in the regenerating salamander limb, especially during dedifferentiation, we analyzed stage-specific protein synthesis pattern in the normal and RA-treated regenerating limbs by metabolic labeling followed by two-dimensional gel electrophoresis. In the regenerating limbs without RA treatment, a few hundred kinds of proteins were found to be synthesized at the stage of wound healing and the total number of protein synthesized increased greatly as regeneration proceeded. The same trend was also observed in the RA-treated regenerating limbs. Interestingly, some protein spots were noted to be either newly synthesized or highly expressed by the RA treatment especially at the stage of dedifferentiation. The results shows that the enhancement of dedifferentiation state after the RA treatment correlates well with the protein synthesis profile, and suggest that those proteins are important for the RA-evoked pattern duplication in the regenerating limbs of salamander.

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Dehydrogenases and aldolase in the regenerating forelimb of the adult newt, Diemictylus viridescens

Cited by 30 publications

References 28 publications

Pattern duplication by retinoic acid treatment in the regenerating limbs of Korean salamander larvae, Hynobius leechii, correlates well with the extent of dedifferentiation

Pattern duplication by retinoic acid treatment in the regenerating limbs of Korean salamander larvae, Hynobius leechii, correlates well with the extent of dedifferentiation

Functional Characterization of the Lin28/let-7 Circuit During Forelimb Regeneration in Ambystoma mexicanum and Its Influence on Metabolic Reprogramming

Protein synthesis pattern analysis in the regenerating salamander limb

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