Search Results (3)

Distinct paradigms, such as the “enzymic latch” and “iron gate” theories, have been proposed to elucidate SOC loss or accumulation, but their relative significance and whether they are mutually exclusive in permafrost peatlands remain unclear. To address this, we evaluated their relative importance and identified the dominant factors controlling SOC stability. Therefore, we employed a space-for-time substitution approach across a permafrost gradient (continuous, discontinuous, and isolated) by systematically quantifying extracellular enzyme activities, iron (Fe) phases, and iron-bound soil organic carbon (Fe-SOC) at various depths (0–10, 10–30, and 30–50 cm) in peatlands. Our results did not support the “enzymic latch” theory, with hydrolytic enzyme activities (β-glucosidase (BG), cellobiohydrolase (CBH), and β-N-acetylglucosaminidase (NAG)) showing positive correlations with phenolics but negative correlations with phenol oxidase (PHO) activity. However, ferrous iron (Fe(II)) was significantly positively correlated with PHO activity, and ferric iron (Fe(III)) stabilized SOC through co-precipitation with it to form Fe-SOC, supporting the “iron gate” theory. Moreover, Fe-SOC decreased from the continuous to the isolated permafrost zone, and with soil depth from 0–10 cm to 30–50 cm. Partial least squares path modeling (PLS-PM) analysis indicated that Fe(III) directly and indirectly (via Fe-SOC and phenolics) affected SOC. Our study demonstrated the primacy of the “iron gate” mechanism in controlling carbon stability in the Great Hing’an Mountains permafrost peatlands, providing new insights for projecting carbon-climate feedback. Full article

SET and MYND Domain-Containing 2 (Smyd-2), a specific protein lysine methyltransferase (PKMT), influences both histones and non-histones. Its role in cerebral ischemia/reperfusion (CIR), particularly in ferroptosis—a regulated form of cell death driven by lipid peroxidation—remains poorly understood. This study identifies the expression of Smyd-2 in the brain and investigates its relationship with neuronal programmed cell death (PCD). We specifically investigated how Smyd-2 regulates ferroptosis in CIR through its interaction with the Nuclear Factor Erythroid-2-related Factor-2 (Nrf-2)/Kelch-like ECH-associated protein (Keap-1) pathway. Smyd-2 knockout protects HT-22 cells from Erastin-induced ferroptosis but not TNF-α + Smac-mimetic-induced apoptosis/necroptosis. This neuroprotective effect of Smyd-2 knockout in HT-22 cells after Oxygen–Glucose Deprivation/Reperfusion (OGD/R) was reversed by Erastin. Smyd-2 knockout in HT-22 cells shows neuroprotection primarily via the Nuclear Factor Erythroid-2-related Factor-2 (Nrf-2)/Kelch-like ECH-associated protein (Keap-1) pathway, despite the concurrent upregulation of Smyd-2 and Nrf-2 observed in both the middle cerebral artery occlusion (MCAO) and OGD/R models. Interestingly, vivo experiments demonstrated that Smyd-2 knockout significantly reduced ferroptosis and lipid peroxidation in hippocampal neurons following CIR. Moreover, the Nrf-2 inhibitor ML-385 abolished the neuroprotective effects of Smyd-2 knockout, confirming the pivotal role of Nrf-2 in ferroptosis regulation. Cycloheximide (CHX) fails to reduce Nrf-2 expression in Smyd-2 knockout HT-22 cells. Smyd-2 knockout suppresses Nrf-2 lysine methylation, thereby promoting the Nrf-2/Keap-1 pathway without affecting the PKC-δ/Nrf-2 pathway. Conversely, Smyd-2 overexpression disrupts Nrf-2 nuclear translocation, exacerbating ferroptosis and oxidative stress, highlighting its dual regulatory role. This study underscores Smyd-2’s potential for ischemic stroke treatment by disrupting the Smyd-2/Nrf-2-driven antioxidant capacity, leading to hippocampal neuronal ferroptosis. By clarifying the intricate interplay between ferroptosis and oxidative stress via the Nrf-2/Keap-1 pathway, our findings provide new insights into the molecular mechanisms of CIR and identify Smyd-2 as a promising therapeutic target. Full article

Ischemic stroke is a devastating condition that occurs due to the interruption of blood flow to the brain, resulting in a range of cellular and molecular changes. In recent years, there has been growing interest in the role of ferroptosis, a newly identified form of regulated cell death, in ischemic stroke. Ferroptosis is driven by the accumulation of lipid peroxides and is characterized by the loss of membrane integrity. Additionally, oxidative stress, which refers to an imbalance between prooxidants and antioxidants, is a hallmark of ischemic stroke and significantly contributes to the pathogenesis of the disease. In this review, we explore the interactions between ferroptosis and oxidative stress in ischemic stroke. We examine the underlying mechanisms through which oxidative stress induces ferroptosis and how ferroptosis, in turn, exacerbates oxidative stress. Furthermore, we discuss potential therapeutic strategies that target both ferroptosis and oxidative stress in the treatment of ischemic stroke. Overall, this review highlights the complex interplay between ferroptosis and oxidative stress in ischemic stroke and underscores the need for further research to identify novel therapeutic targets for this condition. Full article