Apoptosis in pre-Bilaterians: Hydra as a model

Lasi, Margherita; David, Charles N.; Böttger, Angelika

doi:10.1007/s10495-009-0442-7

Cited by 64 publications

(93 citation statements)

References 66 publications

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“…Lasi et al . (2010) showed that transient expression of FoxO‐GFP protein induced an apoptosis rate of 20–60% in Hydra epithelial cells. Conversely, co‐expression of one of the Hydra insulin‐like genes with the FoxO‐GFP protein was shown to decrease the rate of apoptosis in these cells.…”

Section: Animal Modelsmentioning

confidence: 99%

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Long live FOXO: unraveling the role of FOXO proteins in aging and longevity

2015

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SummaryAging constitutes the key risk factor for age‐related diseases such as cancer and cardiovascular and neurodegenerative disorders. Human longevity and healthy aging are complex phenotypes influenced by both environmental and genetic factors. The fact that genetic contribution to lifespan strongly increases with greater age provides basis for research on which “protective genes” are carried by long‐lived individuals. Studies have consistently revealed FOXO (Forkhead box O) transcription factors as important determinants in aging and longevity. FOXO proteins represent a subfamily of transcription factors conserved from Caenorhabditis elegans to mammals that act as key regulators of longevity downstream of insulin and insulin‐like growth factor signaling. Invertebrate genomes have one FOXO gene, while mammals have four FOXO genes: FOXO1, FOXO3, FOXO4, and FOXO6. In mammals, this subfamily is involved in a wide range of crucial cellular processes regulating stress resistance, metabolism, cell cycle arrest, and apoptosis. Their role in longevity determination is complex and remains to be fully elucidated. Throughout this review, the mechanisms by which FOXO factors contribute to longevity will be discussed in diverse animal models, from Hydra to mammals. Moreover, compelling evidence of FOXOs as contributors for extreme longevity and health span in humans will be addressed.

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Section: Animal Modelsmentioning

confidence: 99%

“…Conversely, co‐expression of one of the Hydra insulin‐like genes with the FoxO‐GFP protein was shown to decrease the rate of apoptosis in these cells. As the IIS acts through the PI3K/AKT/SGK pathway, one can hypothesize that the IIS reduces Hydra ′s FoxO activity (Lasi et al ., 2010). …”

Section: Animal Modelsmentioning

confidence: 99%

Long live FOXO: unraveling the role of FOXO proteins in aging and longevity

2015

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“…In the colonial hydrozoan Hydractinia echinata, it is necessary for metamorphosis [11,12]. Recent genome sequencing projects have indicated the presence of large families of apoptotic proteins, including caspases, Bcl-2 family proteins and APAF-1 in cnidarians [13][14][15]. However, their functional interactions and the roles they have in apoptosis are unknown.…”

Section: Introductionmentioning

confidence: 99%

The molecular cell death machinery in the simple cnidarian Hydra includes an expanded caspase family and pro- and anti-apoptotic Bcl-2 proteins

et al. 2010

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The fresh water polyp Hydra belongs to the phylum Cnidaria, which diverged from the metazoan lineage before the appearance of bilaterians. In order to understand the evolution of apoptosis in metazoans, we have begun to elucidate the molecular cell death machinery in this model organism. Based on ESTs and the whole Hydra genome assembly, we have identified 15 caspases. We show that one is activated during apoptosis, four have characteristics of initiator caspases with N-terminal DED, CARD or DD domain and two undergo autoprocessing in vitro. In addition, we describe seven Bcl-2-like and two Bak-like proteins. For most of the Bcl-2 family proteins, we have observed mitochondrial localization. When expressed in mammalian cells, HyBak-like 1 and 2 strongly induced apoptosis. Six of the Bcl-2 family members inhibited apoptosis induced by camptothecin in mammalian cells with HyBcl-2-like 4 showing an especially strong protective effect. This protein also interacted with HyBak-like 1 in a yeast two-hybrid assay. Mutation of the conserved leucine in its BH3 domain abolished both the interaction with HyBak-like 1 and the anti-apoptotic effect. Moreover, we describe novel Hydra BH-3-only proteins. One of these interacted with Bcl-2-like 4 and induced apoptosis in mammalian cells. Our data indicate that the evolution of a complex network for cell death regulation arose at the earliest and simplest level of multicellular organization, where it exhibited a substantially higher level of complexity than in the protostome model organisms Caenorhabditis and Drosophila.

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“…The first and most direct way to inhibit cell death was to prevent caspase activity in regenerating Hydra: for this purpose animals were treated for a short period of time (90 minutes before amputation and up to 90 minutes after) with the Z-VAD-fmk pan-caspase inhibitor (Graczyk 2002). Previous studies performed by the group of Charlie David and Angelika Boettger in Munich had proven that the genetic circuitry supporting apoptosis is well conserved across eumetazoans, and that indeed caspase inhibitors significantly reduce caspase activity in Hydra (Cikala et al 1999;Lasi et al 2010). This short exposure to Z-VAD-fmk was sufficient to efficiently inhibit apoptosis: 75% of the bisected animals exposed to Z-VAD-fmk no longer regenerate their head and actually die within the next days.…”

Section: Injury-induced Apoptosis Is Necessary For Head Regenerationmentioning

confidence: 99%

Injury-induced asymmetric cell death as a driving force for head regeneration in Hydra

Galliot

2012

Dev Genes Evol

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The freshwater Hydra polyp provides a unique model system to decipher the mechanisms underlying adult regeneration. Indeed a single cut initiates two distinct regenerative processes, foot regeneration on one side, head regeneration on the other side, the latter relying on the rapid formation of a local head organizer. Two aspects are discussed here, the asymmetric cellular remodeling induced by mid-gastric bisection and the signaling events that trigger head organizer formation. In head-regenerating tips (but not in foot ones) a wave of cell death takes place immediately, leading the apoptotic cells to transiently release Wnt3 and activate the β-catenin pathway in the neighboring cycling cells to push them through mitosis. This process, which mimics the apoptosis-induced compensatory proliferation process deciphered in Drosophila larvae regenerating their discs likely corresponds to an evolutionarily-conserved mechanism, also at work in Xenopus tadpoles regenerating their tale or mice regenerating their skin or liver. How is this process generated in Hydra? Several studies pointed to the necessary activation of the ERK 1-2 and MAPK pathways during early head regeneration and indeed ERK 1-2 inhibition or RSK, CREB, CBP knockdown prevent injury-induced apoptosis and head regeneration. The current scenario involves an asymmetric activation of the MAPK/CREB pathway to trigger injury-induced apoptosis in the interstitial cells, and, in the epithelial cells a CREB/CBP-dependent transcriptional activation of early genes essential for head organizing activity as wnt3, HyBra1, prdl-a. The question now is how bisection in the rather uniform central region of the polyp can generate this immediately asymmetric signaling.

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Apoptosis in pre-Bilaterians: Hydra as a model

Cited by 64 publications

References 66 publications

Long live FOXO: unraveling the role of FOXO proteins in aging and longevity

Long live FOXO: unraveling the role of FOXO proteins in aging and longevity

The molecular cell death machinery in the simple cnidarian Hydra includes an expanded caspase family and pro- and anti-apoptotic Bcl-2 proteins

Injury-induced asymmetric cell death as a driving force for head regeneration in Hydra

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