Phosphorylated ATM and H2AX in T and B lymphocytes from rats with moderate and severe malnutrition

• Published in: DNA repair 2019-11, Vol.83, p.102640-102640, Article 102640
• Main Authors: González-Gutiérrez, Ana María, Ortiz-Muñiz, Rocío, García-Rodríguez, María del Carmen, Cortés-Barberena, Edith
• Format: Article
• Language: English
• Subjects: Animals; Ataxia Telangiectasia Mutated Proteins - metabolism; ATM; B-Lymphocytes - metabolism; Body Weight; DNA damage; Flow cytometry; H2AX; Histones - metabolism; Malnutrition; Malnutrition - immunology; Malnutrition - metabolism; Phosphoproteins - metabolism; Phosphorylation; Rats; Rats, Wistar; Spleen - immunology; T-Lymphocytes - metabolism
• ISSN: 1568-7864; 1568-7856
• DOI: 10.1016/j.dnarep.2019.102640

Fig. 1. Background and gH2AX assay by flow cytometry. DNA in humans and experimental animals is damaged as a result of malnutrition. In this work, we used flow cytometry to determine whether the ability to recognize double-strand breaks (DSBs) is affected by protein calorie malnutrition (PCM). The results showed increased cellular percentages that pATM (ataxia telangiectasia mutated, phosphorylated at Ser1981) and the histone variant H2AX phosphorylated at serine 139 (gH2AX); pATM is responsible for phosphorylating gH2AX, which indicates DSBs. [Display omitted] •The percentages of pATM + and gH2AX + B and T lymphocytes were measured in rats.•UNM and UNS increased the percentage of pATM + cells in the spleen.•Splenic T and B cells in UNM and UNS rats had the capacity to recognize DNA damage.•The percentage of peripheral blood gH2AX + cells showed an increasing tendency.•Continuity of DNA damage response appears compromised by a deficient nutrient status. Protein calorie malnutrition (PCM) occurs when insufficient nutrients are consumed to satisfy the biological needs of an organism. The literature supports the relationship between malnutrition and DNA damage, and among the injuries to genetic material, DNA double-strand breaks (DSBs) are the most dangerous. This study aimed to determine whether the ability of splenic and peripheral blood T and B lymphocytes from nursing rats to recognize DSB-induced DNA damage is affected by PCM. Wistar strain rats were used, and experimental malnutrition was induced by creating food competition during lactation by increasing the number of offspring per wet nurse. Due to its high specificity, the phosphorylated H2AX variant histone assay associated with pATM (Ser1981) combined with flow cytometry was herein used to demonstrate the impact of malnutrition on the DNA damage response. Flow cytometry data indicated that splenic T and B lymphocytes from rats with severe PCM have the capacity to detect genetic material damage, as shown by an increased number of pATM + cells and altered signaling pathway continuity. Collectively, these data suggest that severe malnutrition compromises the continuity of the DNA damage response.