Biology subjects

Jaramillo Ortiz, S.

Publications and source records attributed to Jaramillo Ortiz, S..

4 recordsLinked to original sources

bioRxiv2026

KDM6B interacts with nucleo-adhesome components CSRP2 and TGFB1I1 to regulate EMT

The methyltransferase EZH2 (Enhancer of Zest Homolog 2) and the demethylase KDM6B (Lysine Demethylase 6B) have been associated with epithelial to mesenchymal transition (EMT) and poor prognosis in various cancers. These enzymes methylate and demethylate H3K27me3 and regulate distinct sets of genes controlling EMT induction, despite having opposite catalytic activities. This could be due to their recruitment or the modulation of their activity by partner proteins on specific loci. This work sought to identify proteins associated with chromatin and interacting with EZH2 or with KDM6B during EMT. To do so, co-immunoprecipitation and mass spectroscopy was used under TGF{beta} (Tumor growth factor {beta}) and TNF (Tumor necrosis factor ) treatment to induce EMT in A549 lung cancer cells. Surprisingly, numerous proteins related to focal adhesions were identified to interact with EZH2 or KDM6B. These proteins are part of a nuclear protein interaction network previously described as nucleo-adhesome. Among these proteins, TGFB1I1 (transforming growth factor induced peptide 1) and CSRP2 (cysteine and glycine rich protein 2) were further confirmed to interact with KDM6B in the nucleus and even more so during EMT. The target genes of these complexes were then sought by knocking down KDM6B, TGFB1I1 or CSRP2. Three genes (coding Integrin alpha 5, Laminin y2 and Matrix Metalloproteinase 9) were confirmed to be regulated by KDM6B, TGFB1I1 and CSRP2. These findings may have clinical relevance, as immunohistochemistry analyses performed on a cohort of lung cancer patients revealed increased nuclear localization of TGFB1I1 and CSRP2 in cells undergoing EMT.

cell biology↗

bioRxiv2026

Decoupling glycation from mortality: glucose, but not methylglyoxal, reduces survival in zebra finches

Birds provide a unique model for ageing research, with greater longevity and slower senescence compared to mammals of similar body size, despite a higher mass-adjusted metabolic rate and blood glucose levels than other vertebrate groups. While the effects of glucose, glycation, and advanced glycation end-products (AGE) on ageing are well-documented in biomedical research, their impact on avian physiology and ageing remains poorly understood. Although birds may possess adaptations mitigating the potential detrimental effects of glucose, elevated glucose still predicts reduced lifespan, and protein glycation varies with age and can influence survival and some fitness-related traits, implying that glycation or AGE accumulation may have relevant effects on avian longevity. In this study, we experimentally investigated how one year of dietary supplementation with glucose or methylglyoxal affects survival and physiology (metabolic rate, flying performance, and beak coloration) in captive zebra finches (Taeniopygia guttata). We reveal a significant increase in mortality exclusively in glucose-supplemented birds, with also an elevated albumin glycation rate and AGE formation. However, these variables did not directly explain the increased mortality, which was also absent in methylglyoxal-treated individuals, despite similar AGE accumulation. Additionally, we observed some other effects, like an age-related constraint on seasonal metabolic adjustment, a treatment-influenced age decline in secondary sexual traits expression, and a decline in flight performance during the peak mortality period, suggesting a broader deterioration of health. Thus, although we demonstrate glucose supplementation to be more deleterious than methylglyoxal, the underlying mechanisms for the increase in mortality induced by the treatment remain unresolved.

physiology↗

bioRxiv2024

Glycaemia and albumin glycation rates as fitness mediators in the wild: the case of a long-lived bird

Glucose is a vital metabolic component in the functioning of organisms, but it can also bind to biomolecules through non-enzymatic glycation reactions that result in loss of functions. While the effects of glycation on health have been well demonstrated in biomedical research, little is known about the effects of glycation in wild animals. Here, we studied how plasma glucose levels and albumin glycation rates vary with age and are related to fitness in a relatively hyperglycaemic long-lived bird, the Alpine swift (Tachymarptis melba). We measured plasma glucose and albumin glycation levels before and after reproduction in adult females of known age (2-14 years), showing that, while glucose levels increased in parallel with body mass, albumin glycation rates decreased within this period. Albumin glycation, but not glucose, varies with age, peaking at 5 years, consistently with other age-related parameters previously reported in this species. Interestingly, higher plasma glucose levels before reproduction were related to increased fledging success up to a certain threshold. In addition, in terms of dynamics, females gaining more mass lowered more their glycation levels, while those gaining less mass and lowering the more their glycation levels laid more eggs. Finally, higher body mass and plasma glucose levels after reproduction predicted a higher survival probability to the next season, whereas higher albumin glycation predicted lower survival, although in an age-dependent manner. Our study highlights adult plasma glucose and glycated albumin levels as new potential markers of ageing and fitness that should be further explored in this species.

evolutionary biology↗

bioRxiv2024

Understanding glycaemia and glycation levels in birds: diet and life history traits associations

The pace of life syndrome hypothesis (POLS) suggests that organisms life history, physiological and behavioural traits should co-evolve. In this framework, how glycaemia (i.e., blood glucose levels) and its reaction with proteins and other compounds (i.e. glycation) covary with life history traits remain relatively under-investigated, despite the well documented consequences of glucose and glycation on ageing, and therefore potentially on life history evolution. Birds are particularly relevant in this context given that they have the highest blood glucose levels within vertebrates and still higher mass-adjusted longevity when compared to organisms with similar physiology as mammals. We thus performed a comparative analysis on glucose and albumin glycation rates of 88 bird species from 22 orders, in relation to life history traits (body mass, clutch mass, maximum lifespan and developmental time) and diet. Glucose levels correlated positively with albumin glycation rates in a non-linear fashion, suggesting resistance to glycation in species with higher glucose levels. Plasma glucose levels decreased with increasing body mass but, contrary to what is predicted to the POLS hypothesis, glucose levels increased with maximum lifespan before reaching a plateau. Finally, terrestrial carnivores showed higher albumin glycation compared to omnivores despite not showing higher glucose, which we discuss may be related to additional factors as differential antioxidant levels or dietary composition in terms of fibres or polyunsaturated fatty acids. These results increase our knowledge about the diversity of glycaemia and glycation patterns across birds, pointing towards the existence of glycation resistance mechanisms within comparatively high glycaemic birds.

evolutionary biology↗