Biology subjects

Suresh, G.

Publications and source records attributed to Suresh, G..

3 recordsLinked to original sources

bioRxiv2026

Hyperglycemia transcriptionally regulates the paranodal protein (Caspr1) in retinal neurons and modulates neurite extension

Hyperglycemia is a hallmark of diabetes, affecting neuronal structure and function by altering molecular signalling pathways. Here, we explore the role of hyperglycemia in regulating Caspr1 expression and its downstream effects on neurite outgrowth. Caspr1, a critical protein implicated in neurodegenerative diseases, was found to be significantly downregulated in N2a and 661W cell lines cultured under hyperglycemic conditions (25mM glucose) and, as a result, promoted neurite outgrowth. Knockout of Caspr1 using CRISPR-Cas9 further confirmed its inhibitory role on neurite outgrowth, as Caspr1-deficient cells exhibited enhanced neurite elongation. Caspr1 downregulation was mediated by decreased expression of C/EBP, a key transcription factor with a binding site on the Caspr1 promoter. Overexpression of C/EBP restored Caspr1 promoter activity and mRNA levels, establishing C/EBP as a critical regulator. Additionally, hyperglycemia was observed to inhibit Akt phosphorylation, which further contributed to Caspr1 downregulation. Adding insulin to the culture medium under hyperglycemic conditions shows inhibition of Akt phosphorylation and downregulation of Caspr1, resulting in a shorter length of neurites in retinal neurons. In vivo, studies in diabetic mouse models and diabetic patient samples demonstrated reduced expression of Caspr1 in retinal tissues. These results suggest that hyperglycemia regulates Caspr1 expression through Akt and C/EBP pathways, promoting neurite outgrowth in retinal neurons. In contrast, adding insulin to the medium under hyperglycemia downregulates the Caspr1 expression and reduces neurite length in retinal neurons. Targeting this pathway may offer new therapeutic approaches to mitigate neurodegeneration in diabetic retinopathy.

cell biology↗

bioRxiv2025

Novel function of Contactin associated protein 1 (Caspr 1)/ Paranodin in embryonic cortical neurons: hypoxia modulated neurite development.

Hypoxia, a condition of inadequate oxygen supply, is a common phenomenon affecting neurons and brain tissue, leading to significant implications for neuronal health and function. The prevalence of hypoxia in the brain is associated with various neurological conditions, making it a critical area of study. Neuritogenesis, the process of neurite outgrowth, is an essential aspect of neuronal development and connectivity and is particularly sensitive to hypoxic stress. Investigating how hypoxia affects neurite outgrowth is vital for understanding neuronal response and adaptation under low oxygen conditions. This study explores how hypoxic stress affects neurite regulation mediated by Contactin Associated Protein-1 (Caspr1) in primary mouse embryonic cortical neurons. Hypoxia, induced by culturing neurons in a 2% oxygen environment, significantly reduced neurite length and induced notable changes in growth cone morphology. Concurrently, we observed an upregulation in the expression of Caspr1 and its transcriptional regulator C/EBP, suggesting a compensatory role for Caspr1 in neurite extension under low oxygen conditions. Shorter hypoxia exposure periods revealed a dynamic biphasic response in Caspr1 levels, with an initial decrease followed by a substantial increase, correlating with corresponding changes in neurite length. This pattern emphasizes the critical involvement of Caspr1 in adapting neurite growth to fluctuating hypoxia duration. Furthermore, comparative analyses using wild-type and Caspr1 knockout Neuro2a cells demonstrated that the absence of Caspr1 mitigates hypoxia-induced neurite shortening, indicating a potential protective role against hypoxic stress. Additionally, hypoxia profoundly impacted mitochondrial morphology and function. Under hypoxic conditions, mitochondria transitioned to a more spherical shape. Mitochondrial respiration analysis revealed significant reductions in oxygen consumption rates (OCR), highlighting compromised mitochondrial function during hypoxia. These findings underscore the multifaceted role of Caspr1 in neurite regulation and mitochondrial adaptation to hypoxic stress. The study provides insights into the molecular mechanisms underpinning hypoxia-induced changes in neuronal morphology and function. Understanding these processes opens avenues for therapeutic strategies targeting Caspr1 in treating neurological disorders characterized by hypoxic stress. Future research will benefit from extending these investigations to more complex models, such as brain organoids, to further elucidate the metabolic and structural changes under hypoxia and their implications for neurodegenerative diseases.

neuroscience↗

bioRxiv2017

Supplement comprising of laccase and citric acid as an alternative for antibiotics - in vitro triggers of melanin production

An indiscriminate use of antibiotics in humans and animals has led to a widespread selection of antibiotic-resistant bacterial strains. A possible solution to counter this problem could be to develop alternatives that may boost the host immunity, thus reducing in the quantity and frequency of antibiotic use. In this work, for the first time, citric acid and laccase were used as extracellular inducers of melanin production in yeast cells and human cell lines. It is proposed that the formulation of laccase and citric acid together could further promote melatonin stimulated melanocyte derived melanin production. Melanization test as a probe of immunity, described in this study, is an easy and a quicker test than the other immunity tests and is statistically significant. The results showed the synergistic effect of citric acid and laccase on melanin production by the yeast cells, with significant statistical differences compared to all other tested conditions (P: 0.0005- 0.005). Laccase and citric acid together boosted melanin production after 8 days of incubation. An increase in melanin production by two colon human cells lines (Cacao-2/15 and HT-29) was observed when both laccase and citric acid were present in cell growth medium. A formulation with citric acid and laccase may prove to be an excellent alternative to reduce the antibiotic load in human and animal subjects.\n\nSummary statementThis study shows, for the first time, that production of melanin in yeast and human intestinal cells is induced by extracellular addition of laccase and citric acid.

immunology↗