Biology subjects

GOMEZ MEJIBA, S. E.

Publications and source records attributed to GOMEZ MEJIBA, S. E..

3 recordsLinked to original sources

bioRxiv2024

VITAMIN A DEFICIENCY CAUSES APOPTOSIS IN THE MAMMARY GLAND OF RATS

Subchronic dietary vitamin A deficiency (VAD) causes severe abnormalities, including dysfunction of the epithelia of the mammary gland. However, the underlying mechanism of this process is partially known. Therefore, herein, we used a nulliparous-rat experimental model of dietary VAD for a total dieting regime of 3 and 6 months and intervened (refeed) with a vitamin A sufficient (VAS) diet for 0.5 or 1 month before the end of the diet regime and investigated the underlying molecular mechanism of mammary tissue dysfunction. Dietary vitamin A deficiency for 3 and 6 months caused increased inflammatory cell infiltration in the mammary gland parenchyma and glandular cells, with increased inflammation and apoptosis and reduced cell proliferation. These changes can be reversed with a VAS diet. Mammary gland dysfunction after a subchronic VAD is caused by an imbalance between NF{kappa}B and retinoic acid-triggered signaling. Inflammation, apoptosis, and impaired proliferation lead to dysfunction of the epithelia of the mammary gland of nulliparous rats fed a VAD diet.

biochemistry↗

bioRxiv2024

Trapping DNA-radicals with DMPO reduced hypochlorous acid-induced 8-oxo-7,8-dihydro-2'-deoxyguanosine and mutagenesis in lung epithelial cells

Irritation causes the recruitment and activation of neutrophils in the stressed airways. This process is known as neutrophilic inflammation. This process results in myeloperoxidase (MPO), an enzyme contained inside neutrophil azurophilic granules, being released as neutrophil extracellular traps (NETs), which also contain genomic DNA, modified histones, and other proteins. In the airways, released MPO can be taken up by bystander tissue epithelial cells. MPO is the only mammalian peroxidase enzyme that under physiological conditions produces hypochlorite (HOCl). Intracellularly produced HOCl may damage the cell genome, with the intermediacy of DNA-centered free radicals, which upon reaction with molecular oxygen decay to mutagenic end-oxidation products, such as 8-oxo-7,8-dihydro-2 -deoxyguanosine (8-oxo-dGuo). Herein, we aimed to test whether HOCl-induced DNA-centered radicals precede the oxidation of DNA and mutagenesis in A549 human lung epithelial cells as an in vitro model that resembles neutrophilic inflammation in irritated airways. Interestingly, by trapping HOCl-induced DNA-centered radicals, the nitrone spin trap 5,5-dimethyl-1-pyrroline N-oxide (DMPO) blocks the formation of 8-oxo-dGuo and possibly other end-oxidation products, forming DNA-DMPO nitrone adducts, thus reducing mutagenesis in the hypoxanthine phosphoribosyl transferase (hrpt) gene, one of the most sensitive genes to oxidative damage. P53 is a transcription factor known as the master regulator of the cell response to genomic damage. By trapping DNA-centered radicals, DMPO also blocks the translocation of p53 to the cell nucleus, suggesting that by trapping DNA-centered radicals with DMPO, end-oxidation products are prevented, and the cell response to genomic damage is not sensed. DMPO traps DNA-centered radicals, reduces 8-oxo-dGuo accumulation, and blocks hrpt gene mutation. Trapping DNA-centered radicals to reduce the accumulation of HOCl-induced mutagenic end-oxidation products in the genome of bystander cells, which have taken MPO from the inflammatory milieu, will provide new therapeutic avenues to reduce genotoxic damage at sites of neutrophilic inflammation, such as in the irritated airways.

biochemistry↗

bioRxiv2024

Exotoxins secreted by Clostridium septicum induce macrophage death: implications for bacterial immune evasion mechanisms at infection sites

The induction of macrophage death is regarded as a potential mechanism by which components secreted by Clostridium septicum are used to evade the innate immune response and cause tissue damage. This study aimed to determine the effect of partially purified fractions of extracellular proteins secreted by C. septicum on the death of mouse peritoneal macrophages. Elicited mouse peritoneal macrophages were incubated with partially purified fractions of proteins secreted by C. septicum into the culture medium. After incubation, we found that the protein fraction with a molecular weight [≥] 100 kDa caused significant cell death in macrophages, changed cell morphology, increased markers of apoptosis and autophagy, and increased the expression (protein and mRNA) of IL-10 and TNF Our data suggest that the proteins secreted by C. septicum (MW, [≥] kDa) induce cell death in macrophages by promoting autophagy- triggered apoptosis. This study may contribute to our understanding of the molecular mechanism of immune evasion by C. septicum at the infection site.

microbiology↗