Advanced Glycation End-Products Sensitize Human Sensory-Like Neuron Cells to Capsaicin-Induced Calcium Influx

Author(s)

Silva, Gessica Sabrina de Assis ; Bufalo, Michelle Cristiane ; Souza, Marcelo Medina de ; DeOcesano-Pereira, Carlos ; Chudzinski-Tavassi, Ana Marisa ; Zambelli, Vanessa Olzon

• Document type: Journal article
• Source: JOVE-JOURNAL OF VISUALIZED EXPERIMENTS; v. N/A, n. 219, p. 13-pg., 2025-05-01.

Abstract

Increased collagen-derived advanced glycation end products (AGEs) are consistently linked to painful diseases, including osteoarthritis, diabetic neuropathy, and neurodegenerative disorders. Human sensory-like neurons differentiated from the SH-SY5Y cell line gain pro-nociceptive functions when exposed to AGEs by releasing substance P and upregulating the transient receptor potential vanilloid 1 (TRPV1) expression. Here, we investigated whether this receptor was functionally active and whether the glycation process sensitizes sensory neurons to capsaicin excitation. Sensory-like neuron cells were obtained from the differentiation of SH-SY5Y cells with all-trans-retinoic acid and brain-derived neurotrophic factor. Incubation with glycated collagen extracellular matrix (ECM-GC) simulated a pro-nociceptive stimulus. Control cells were incubated with a non-glycated extracellular collagen matrix (ECM-NC). Fluo-8 Calcium Flux Assay Kit was used to assess calcium influx, which was stimulated by capsaicin. The results show that glycation increases calcium influx compared with cells treated with normal collagen, suggesting that sensory-like neurons express functional TRPV1 channels and that glycation increases capsaicin excitation. These data indicate AGEs hypersensitive sensory-like neuron cells, triggering pro-nociceptive signaling. Together, our results suggest that we established a functional model responsive to capsaicin that can be useful for screening candidates for managing painful conditions. (AU)

• FAPESP's process: 15/50040-4 - Rational approach for searching molecular targets involved in inflammatory events and cell survival
• Grantee: Ana Marisa Chudzinski-Tavassi
• Support Opportunities: Research Grants - Applied Research Centers Program
• FAPESP's process: 22/08417-7 - Role of Advanced Glycation Endproducts on Neuronal Degeneration and their Contribution to the Development of Peripheral Neuropathy
• Grantee: Gessica Sabrina de Assis Silva
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 20/13139-0 - Centre of Excellence in New Target Discovery
• Grantee: Ana Marisa Chudzinski-Tavassi
• Support Opportunities: Research Grants - Applied Research Centers Program
• FAPESP's process: 24/04023-0 - Aldehyde Dehydrogenase-2 Involvement in the Alcoholic Neuropathic Pain Developing in Mice
• Grantee: Vanessa Olzon Zambelli
• Support Opportunities: Regular Research Grants