Modern Approaches to the Assessment of Biological Markers of Autophagy and Apoptosis in Acute Ischemic Stroke

Autoimmune thyroiditis (AIT) is a chronic thyroid disorder wherein overstimulated CD4+T lymphocytes activate CD8+ cytotoxic T lymphocytes, thereby inducing Fas-mediated apoptosis of thyrocytes and reducing the hormonal activity of the thyroid gland. Recent studies suggest that autophagy, a process vital for maintaining cellular homeostasis through the degradation of damaged proteins and organelles in autolysosomes, is involved in the pathogenesis of autoimmune diseases. This article examines autophagy in peripheral blood mononuclear cells and the expression of key autophagy proteins (Vps34, p62, and LC3) in patients with AIT. The number of autophagosomes in the cells was tracked and assessed using flow cytometry. The expression of the protein markers was measured by western blotting. It was demonstrated that the levels of Vps34, LC3-II, and p62 increased significantly in the lymphocytes of all patients with AIT. The high level of the autophagosome protein LC3-II correlated with that of the ubiquitin-binding protein p62, which may indicate a disruption in the late stage of autophagy, i.e., in the fusion of autophagosomes with lysosomes. Impaired autophagy promotes excessive accumulation of autophagosomes in the cytoplasm, which, in turn, triggers apoptotic or necrotic cell death. Therefore, understanding the mechanisms of impaired autophagy in lymphocytes could be a promising avenue for slowing and limiting the damage associated with the onset and development of AIT.

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Intranasal Insulin Decreases Autophagic and Apoptotic Death of Neurons in the Rat Hippocampal C1 Region and Frontal Cortex Under Forebrain Ischemia–reperfusion

Fokina,

Zakharova,

Bayunova

et al. 2023

Žurnal èvolûcionnoj biohimii i fiziologii

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The development of approaches to therapy of ischemic brain injuries requires a better insight into the mechanisms that regulate both apoptotic and autophagic death of neurons. Under a strong ischemic (or other pathological) exposure, neurons can die from the activation of both apoptosis and autophagy. This work was aimed to assess the contribution of autophagy and apoptosis activation to neuronal cell death in the hippocampal CA1 region and frontal cortex using the rat two-vessel occlusion/hypotension model of global forebrain ischemia with subsequent long-term reperfusion, as well as to study the ability of intranasal insulin to prevent autophagic and apoptotic death of neurons. The inhibitors of autophagy (3-methyladenine), apoptosis (Ac-DEVD-CHO), or phosphate buffer (for control) were administered to rats intracerebroventricularly before ischemia and reperfusion. To count viable neurons, brain sections were stained with a Nissl stain. During ischemia–reperfusion, the number of viable neurons in the hippocampal CA1 region decreased by 58.3 ± 1.5% of their count in sham-operated rats (control taken as 100%). The administration of autophagy or apoptosis inhibitors increased the number of viable neurons in the hippocampal CA1 region from 58.3 ± 1.5% to 90.4 ± 2.2% (p 0.001) and 71.6 ± 1.8% (p 0.001) vs. control, respectively. Intranasal insulin administration at a dose of 0.5 IU (before ischemia and at a daily basis for 7 days during reperfusion) normalized the number of viable neurons in the hippocampal CA1 region up to 100.2 ± 1.95% vs. control. In the frontal cortex, the viability of neurons also decreased under ischemia–reperfusion, while the number of viable neurons increased after the administration of autophagy or apoptosis inhibitors, and even to a greater extent after intranasal insulin administration. The main difference was a lower sensitivity of cortical vs. hippocampal neurons to ischemia–reperfusion. These data indicate that intranasal insulin is able to decrease the death of brain neurons caused by the activation of autophagy and apoptosis due to ischemia–reperfusion.

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Modern Approaches to the Assessment of Biological Markers of Autophagy and Apoptosis in Acute Ischemic Stroke

Cited by 3 publications

References 10 publications

Intranasal Insulin Decreases Autophagic and Apoptotic Death of Neurons in the Rat Hippocampal C1 Region and Frontal Cortex under Forebrain Ischemia–Reperfusion

Intranasal Insulin Decreases Autophagic and Apoptotic Death of Neurons in the Rat Hippocampal C1 Region and Frontal Cortex under Forebrain Ischemia–Reperfusion

Autophagy in Mononuclear Cells from Patients with Autoimmune Thyroiditis

Intranasal Insulin Decreases Autophagic and Apoptotic Death of Neurons in the Rat Hippocampal C1 Region and Frontal Cortex Under Forebrain Ischemia–reperfusion

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