α‑enolase and γ‑enolase expression in enriched S- and N-type SH-SY5Y cells : regulatory role of cathepsin X

Horvat, Selena (avtor), Zidar, Nace (avtor), Kos, Janko (avtor), Pišlar, Anja (avtor)

Enolase is well-known for its role in glycolysis but also plays other roles in the central nervous system, including neuronal survival, differentiation, and axonal regeneration. Here, we investigated α- and γ-enolase expression patterns and their association with cathepsin X in distinct SH-SY5Y cell phenotypes. Enriched substrate-adherent S-type cells are characterized by large, flat morphology with extensive cytoplasm and higher expression of vimentin, while neuroblastic N-type are recognized by neurite extensions and higher expression of B-cell lymphoma 2 (Bcl-2) and growth-associated protein-43. We demonstrated that γ-enolase expression was specific to N-type cells, whereas α-enolase expression was not phenotype-specific. Moreover, a shift from ubiquitously expressed α-enolase to neuron-specific γ-enolase was observed during the enrichment and differentiation. Additionally, cathepsin X exhibited higher proteolytic activity in S-type cells. Inhibition of cathepsin X with AMS36 promoted differentiated cell morphology and increased expression of the active form of γ-enolase. Furthermore, AMS36 altered the expression of vimentin and Bcl-2, indicating a regulatory role in neuronal differentiation. Furthermore, AMS36 activated extracellular signal-regulated kinase 1/2 in N-type cells and enhanced the association between γ-enolase and tyrosine receptor kinase in both, suggesting a link between cathepsin X/γ-enolase and the key signaling pathways of differentiation. Our findings underscore the multifaceted role of enolase isoforms in SH-SY5Y cell differentiation, with α-enolase and γ-enolase showing distinct expression patterns in S- and N-type cells. The expression and activity of cathepsin X in S-type cells, along with its regulatory impact on γ-enolase in N-type cells, highlight the importance of these proteins in neuronal differentiation.

• Jezik: Angleški jezik
• Ključne besede: neuron-like cells, neuronal diferentiation, SH-SY5Y cell phenotypes, enolase isoforms, cathepsin X inhibition
• Vrsta gradiva: Članek v reviji
• Tipologija: 1.01 - Izvirni znanstveni članek
• Organizacija: FFA - Fakulteta za farmacijo
• Status publikacije: Objavljeno
• Različica publikacije: Objavljena publikacija
• Leto izida: 2025
• Št. strani: Str. 10006–10019
• Številčenje: Vol. 62, iss. 8
• PID: 20.500.12556/RUL-178431
• UDK: 577.152.34
• ISSN pri članku: 1559-1182
• DOI: 10.1007/s12035-025-04898-2
• COBISS.SI-ID: 231412483
• Datum objave v RUL: 27.01.2026

Gradivo je del revije

• Naslov: Molecular neurobiology
• Skrajšan naslov: Mol. neurobiol.
• Založnik: Springer Nature
• ISSN: 1559-1182
• COBISS.SI-ID: 513709593

Licence

• Licenca: CC BY 4.0, Creative Commons Priznanje avtorstva 4.0 Mednarodna
• Povezava: http://creativecommons.org/licenses/by/4.0/deed.sl
• Opis: To je standardna licenca Creative Commons, ki daje uporabnikom največ možnosti za nadaljnjo uporabo dela, pri čemer morajo navesti avtorja.

Sekundarni jezik

• Jezik: Slovenski jezik
• Ključne besede: nevronom podobne celice, nevronska diferenciacija, fenotipi celic SH-SY5Y, izoforme enolaze, katepsin X zaviralci, katepsin

Projekti

• Financer: ARRS - Agencija za raziskovalno dejavnost Republike Slovenije
• Številka projekta: P4-0127
• Naslov: Farmacevtska biotehnologija: znanost za zdravje

• Financer: ARRS - Agencija za raziskovalno dejavnost Republike Slovenije
• Številka projekta: P1-0208
• Naslov: Farmacevtska kemija: načrtovanje, sinteza in vrednotenje učinkovin