The Basic Biology of Apoptosis and its Implications for Pediatric Surgery

Abstract

Apoptosis, or programmed cell death, is an evolutionarily conserved and highly regulated process of nonfunctional cell death. Through this process, the body disposes of unwanted cells by self-destruction: it is our final defense against damaged cells. In the last decades, many of the essential pathways that control this phenomenon have been elucidated. Apoptosis plays an important role in developmental processes, as well as in cellular homeostasis. This process is known to be accelerated or diminished in many pathologic states. Therefore the understanding of apoptotic regulation has significant clinical ramifications. This article reviews the basic understanding of programmed cell death with respect to areas of interest to pediatric surgeons, including: Hirschsprung disease, intestinal atresias, testicular disorders, short bowel syndrome, ischemia-reperfusion injury and pediatric oncology. Pro or antiapoptotic interventions may become a future target for cell and organ protection in patients suffering from these diseases.

Résumé

Buts: L'apoptose ou la mort cellulaire programmée est un processus très important et précisément régulé de la mort des cellules non fonctionnelles. Par ce processus, le corps dispose de moyens d'autodestruction des cellules non désirées et c'est notre plus grande défense contre les cellules endommagées. Dans les dernières décades, nombre des mécanismes qui contrôlent ce phénomène ont été expliqués. L'apoptose jour un rôle important dans les processus de développement comme dans l'homéostasie cellulaire. Ce processus est connu pour être accéléré ou diminué dans de nombreux états pathologiques. Néanmoins, la compréhension de la régulation de l'apoptose a de multiples ramifications. Cet article revoit la compréhension basique de la mort cellulaire programmée avec des points particuliers d'intérêt pour le chirurgien-pédiatre incluant la Maladie de Hirschsprung, l'atrésie intestinale, les désordres testiculaires, le grêle court, le traumatisme de l'ischémie reperfusion et l'oncologie pédiatrique. Le traitement pour ou anti apoptose peuvent devenir les futures cibles pour protéger les cellules et l'organe chez les patients souffrant de ces maladies.

Resumen

La apoptosis o muerte celular programada es un proceso conservado evolutivamente y altamente regulado de muerte de células no funcionales. Así elimina el cuerpo por autodestrucción células indeseadas siendo el mejor mecanismo de defensa contra las células dañadas. En las últimas décadas han sido elucidadas muchas de las vías que controlan este fenómeno. La apoptosis juega un papel importante en procesos de desarrollo así como en homeostasis celular. Se sabe que está aumentada o disminuida en muchas condiciones patológicas. Por lo tanto la comprensión de la regulación de la apoptosis tiene repercusiones clínicas significativas. Este artículo revisa el conocimiento básico de la muerte celular programada con respecto a áreas de interés para cirujanos pediatras que incluyen la enfermedad de Hirschsprung, las atresias intestinales, trastornos testiculares, intestino corto, isquemia-reperfusión y oncología. Intervenciones pro o anti-apoptóticas pueden constituir objetivos futuros para la protección de células y órganos en pacientes que sufren estas enfermedades.

Zusammenfassung

Die Apoptosis oder der programmierte Zelltod ist ein evolutionärer, erhaltender und hoch regulierter Prozess des nicht funktionellen Zelltods. Durch diesen Prozess stößt der Körper unerwünschte Zellen durch Selbstzerstörung ab. Die Apoptosis ist somit eine der wichtigsten Abwehrmaßnahmen gegen Zellschäden. In den letzten Jahrzehnten wurden viele der wichtigsten Verfahrensweisen dieses Phänomens aufgeklärt. Dabei zeigte es sich, dass die Apoptose eine zentrale Rolle bei Entwicklungsprozessen und der zellulären Homeostase spielt. Es ist bekannt, dass der Prozess viele pathologische Stadien beschleunigen oder verlangsamen kann. Deshalb hat das Verständnis der apoptotischen Regulationsmechanismen eine entscheidende klinische Bedeutung. In der vorliegenden Arbeit werden die Grundlagen des programmierten Zelltodes im Hinblick auf kinderchirurgische Aspekte dargelegt. Insbesondere die Hirschsprungsche Erkrankung, intestinale Atresien, Hodenerkrankungen, das Kurzdarmsyndrom, der Ischämie-Reperfusionsschaden und die pädiatrische Onkologie werden angesprochen. Pro- oder antiapoptotische Maßnahmen werden in Zukunft das Ziel sein, um organschützend bei Patienten, die an diesen Erkrankungen leiden, vorgehen zu können.

Key words

Apoptosis - cell death - diseases - pediatric surgery

Mots-clés

Apoptose - mort cellulaire - maladies - chirurgie pédiatrique

Palabras clave

Apoptosis - muerte celular - enfermedades - cirugía pediátrica

Schlüsselwörter

Apoptosis - Zelltod - Kinderchirurgie - Regulationsmechanismen

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