Summary
The normal senescent fibroblasts in culture accumulate a significantly high proportion of altered enzymes, and the alterations are considered to be the manifestation of ageing in molecular terms. To detect the possible molecular alterations in patients with De Sanctis-Cacchione syndrome, the severest form of xeroderma pigmentosum, in which repair processes to UV light-damaged DNA are defective and the neurologic abnormalities are considered to reflect accelerated ageing, we studied the heat stability of glucose-6-phosphate dehydrogenase (G6PD) in crude extracts of cultured skin fibroblasts. Three patients with the syndrome were the center of our investigation. Even at early passage in culture the heat-labile portion of G6PD was increased in the cells from patients in comparison to normal controls.
The life span of the cells in culture from patients was not reduced below normal age-matched controls, and no appreciable senescent appearance was observed. The increase in the heat-labile portion of G6PD from cells of De Sanctis-Cacchione syndrome patients to reflect that defective repair of DNA damage occurs, rather than being a direct result of ageing of cultured cells.
Zusammenfassung
Die normalen gealterten Fibroblasten zeigen einen signifikanten hohen Anteil veränderter Enzyme. Diese Veränderungen werden als molekularbiologische Zeichen des Alterns betrachtet. Um die möglichen moleckularen Veränderungen mit De Sanctis-Cacchione-Syndrom, der schwersten Form des Xeroderma pigmentosum, bei dem Repair-Mechanismen auf UV der DNA defekt sind und die neurologischen Abnormalitäten offenbar einen beschleunigten Altersvorgang belegen, wurde die Hitzestabilität der Glucose-6-Phosphat-Dehydrogenase in rohen Extrakten von Hautfibroblastenkulturen untersucht. Es standen drei Patienten zur Untersuchung zur Verfügung. Bei den frühesten kulturellen Passagen zeigte sich der hitzelabile Anteil der Glucose-6-Phosphat-Dehydrogenase in den Zellen der Patienten vermehrt im Vergleich mit den normalen Kontrollen. Die Überlebenszeit der Zellkulturen zeigten keinen Unterschied zu den der Kontrollen. Es wurden keine bemerkenswerte Alterserscheinungen beobachtet. Der Anstieg der hitzelabilen Glucose-6-Phosphat-Dehydrogenase in Zellen der Patienten mit De Sanctis-Cacchione-Syndrom scheinen mehr direkt auf einen defekten Repair-Mechanismus der DNA hinzuweisen als sich aus dem Altern der Zellkulturen ableiten zu lassen.
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Okada, N., Kitano, Y. Heat-labile glucose-6-phosphate dehydrogenase in cultured fibroblasts from patients with De Sanctis-Cacchione syndrome. Arch Dermatol Res 271, 341–346 (1981). https://doi.org/10.1007/BF00409462
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DOI: https://doi.org/10.1007/BF00409462