RESUMEN
OBJECTIVE: Cerebral ischemia (CI) is a condition in which metabolic stress increases when blood flow is interrupted in a part of the brain, resulting in oxygen and glucose deprivation. It is known that asprosin (Asp), secreted from adipose tissue during fasting, has an effect on some metabolic processes such as apoptosis, autophagy, and glucose metabolism. This study aimed to explain which of the cell death/survival Asp induces in the CI/reperfusion model. MATERIALS AND METHODS: In the study, 48 male Wistar Albino rats were divided into 6 groups: Sham, CI, Asp+CI, CI+Asp, CI+Asp+3-MA, and Asp+CI+3-MA (n=48). CI was created using the intraluminal filament technique for 60 minutes, autophagy inhibitor 3-MA (15 mg/kg/day) and Asp (1 µg/kg/day) injections were administered 3 days before or 3 days during reperfusion. Beclin-1, ATG5, ATG7, p62, Bcl-2, Bax, active-caspase-3, and active-caspase-9 protein levels from brain tissues were determined by the Western-Blot method. The infarct area was determined by triphenyl tetrazolium chloride (TTC) staining. The Kruskal-Wallis' test was used to compare differences between groups. p<0.05 was considered statistically significant. RESULTS: Compared to the Sham group, the increase in ischemic area and the decrease in Beclin-1, ATG-5, ATG-7, Bcl-2, Bax, active-caspase-3 and active-caspase-9 levels in the CI groups are statistically significant (p<0.05). The increase of Beclin-1, ATG-7, Bcl-2, and Bax levels in the Asp groups is statistically significant compared to the CI group (p<0.05). When Asp+CI groups and CI+Asp groups are compared, an increase in Beclin-1 levels in the Asp+CI group and the increase in Bcl-2, Bax, active-caspase-3/9 and ATG-5 levels in the CI+Asp groups are statistically significant (p<0.05). CONCLUSIONS: Asp has protective and therapeutic effects against CI/R damage. While applying Asp before ischemia activates the autophagy pathway more, applying it after ischemia protects the neuronal death/survival balance by activating the apoptosis pathway more.
Asunto(s)
Lesiones Encefálicas , Infarto Cerebral , Masculino , Ratas , Animales , Caspasa 3 , Caspasa 9 , Beclina-1 , Proteína X Asociada a bcl-2 , Ratas Wistar , Apoptosis , AutofagiaRESUMEN
OBJECTIVE: Diabetes mellitus (DM)-mediated impaired glucose metabolism increase in the glioblastoma (GB) risk by inducing hyperglycemia and hyperinsulinemia. An integral membrane transport protein, glucose transporter 3 (GLUT3) facilitates glucose transport into GB tumor cells. We aimed to explore the regulation of GLUT3 in GB tumors of patients who were concurrently diagnosed with DM. PATIENTS AND METHODS: Formalin-fixed paraffin-embedded (FFPE) tumor samples were collected from 93 GB patients and retrospectively analyzed. Of the total, 15 patients were concurrently diagnosed with DM (GB-DM). The role of GLUT3 in tumor aggressiveness was evaluated by analyzing its correlation with Ki67, P53 expression, MALAT1 expression, and peripheral blood hemoglobin A1C (HbA1c) level. T98G cells were treated with empagliflozin and metformin to modulate GLUT3. The RNA expression of GLUT3, SOX2, and MALAT1 was analyzed by real-time qPCR. The lactate levels of T98G cells were measured by Cobas c502 analyzer. A scratch wound assay was performed to investigate the migration rate of T98G cells. RESULTS: GLUT3 expression was lower in GB-DM tumors than in GB-only tumors. In GB-DM, the expression of tumoral GLUT3 and peripheral blood glycated hemoglobin (HbA1c) levels were negatively correlated with P53 and Ki67. A decreased GLUT3 shortened the disease-free survival duration in GB-DM patients. Empagliflozin reduced GLUT3, while metformin-induced GLUT3 in T98G cells. The empagliflozin-mediated GLUT3 suppression induced SOX2 and MALAT1 expressions and influenced the migration capacity of T98G cells. CONCLUSIONS: Our findings suggest that the low GLUT3 expression of the tumors of GB-DM patients may induce the production of adenosine triphosphate (ATP) from cellular energy sources other than glucose metabolism. However, further studies are warranted to confirm these results.