The advanced glycation end product Nϵ -carboxymethyllysine and its precursor glyoxal increase serotonin release from Caco-2 cells.
Ann-Katrin HolikBarbara LiederNicole KretschyMark M SomozaJakob P LeyJoachim HansVeronika SomozaPublished in: Journal of cellular biochemistry (2017)
Advanced glycation end products (AGEs), comprising a highly diverse class of Maillard reaction compounds formed in vivo and during heating processes of foods, have been described in the progression of several degenerative conditions such as Alzheimer's disease and diabetes mellitus. Nϵ -Carboxymethyllysine (CML) represents a well-characterized AGE, which is frequently encountered in a Western diet and is known to mediate its cellular effects through binding to the receptor for AGEs (RAGE). As very little is known about the impact of exogenous CML and its precursor, glyoxal, on intestinal cells, a genome-wide screening using a customized microarray was conducted in fully differentiated Caco-2 cells. After verification of gene regulation by qPCR, functional assays on fatty acid uptake, glucose uptake, and serotonin release were performed. While only treatment with glyoxal showed a slight impact on fatty acid uptake (P < 0.05), both compounds reduced glucose uptake significantly, leading to values of 81.3% ± 22.8% (500 μM CML, control set to 100%) and 68.3% ± 20.9% (0.3 μM glyoxal). Treatment with 500 μM CML or 0.3 μM glyoxal increased serotonin release (P < 0.05) to 236% ± 111% and 264% ± 66%, respectively. Co-incubation with the RAGE antagonist FPS-ZM1 reduced CML-induced serotonin release by 34%, suggesting a RAGE-mediated mechanism. Similarly, co-incubation with the SGLT-1 inhibitor phloridzin attenuated serotonin release after CML treatment by 32%, hinting at a connection between CML-stimulated serotonin release and glucose uptake. Future studies need to elucidate whether the CML/glyoxal-induced serotonin release in enterocytes might stimulate serotonin-mediated intestinal motility.
Keyphrases
- chronic myeloid leukemia
- induced apoptosis
- fatty acid
- cell cycle arrest
- genome wide
- blood glucose
- type diabetes
- gene expression
- physical activity
- high glucose
- signaling pathway
- blood pressure
- metabolic syndrome
- endoplasmic reticulum stress
- oxidative stress
- drug induced
- cognitive decline
- weight loss
- current status
- staphylococcus aureus
- high throughput
- skeletal muscle
- south africa
- pi k akt
- smoking cessation
- insulin resistance
- replacement therapy