SIRT1 Attenuates Oxyhemoglobin-Induced Oxidative Stress, Mitochondrial Dysfunction, and Apoptosis in Neuronal Cells
Year: 2026
Type: article
Abstract: Early brain injury after aneurysmal subarachnoid hemorrhage (SAH) is driven by exposure of cortical neurons to oxyhemoglobin (OxyHb) released from lysed blood in the subarachnoid space, triggering oxidative stress, mitochondrial dysfunction, inflammation, and apoptosis that contribute to poor neurological outcomes. Sirtuin-1 (SIRT1) is a NAD⁺-dependent deacetylase with antioxidant and anti-apoptotic properties, but its role in OxyHb-mediated neuronal injury remains incompletely defined. An in vitro early brain injury model was established by exposing SH-SY5Y neuronal cells to OxyHb. SIRT1 activity was pharmacologically enhanced with resveratrol or inhibited with EX-527. Neuronal viability, mitochondrial ATP content, reactive oxygen species generation, and expression of SIRT1, Nrf2/HO-1, NF-κB p65, Bax, Bcl-2, cleaved caspase-3, and inflammatory cytokines (TNF-α, IL-6) were assessed using MTT assay, ATP luminescence, DCFDA fluorescence, Western blotting, quantitative PCR, and microscopy. OxyHb exposure significantly reduced neuronal viability and ATP levels, increased oxidative stress, activated NF-κB signaling, and promoted pro-inflammatory and pro-apoptotic pathways while suppressing SIRT1 and Nrf2/HO-1 expression. Pharmacological activation of SIRT1 with resveratrol partially reversed these effects by restoring mitochondrial bioenergetics, enhancing antioxidant defenses, reducing ROS accumulation, suppressing NF-κB–dependent cytokine expression, and shifting apoptotic signaling toward cell survival. In contrast, SIRT1 inhibition with EX-527 aggravated OxyHb-induced oxidative, mitochondrial, inflammatory, and apoptotic injury. Overall, these findings demonstrate that SIRT1 is a central regulator of neuronal responses to OxyHb and that SIRT1 activation confers protection against key pathological processes underlying early brain injury after SAH, supporting its potential as an adjunctive therapeutic target. Further validation in vivo may clarify translational relevance for clinical application.
Institution: Baoding No.1 Central Hospital
Language: English
Subfield: Geriatrics and Gerontology
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W7162241981