The role of telomerase reverse transcriptase in the mitochondrial protective functions of Angiotensin-(1-7) in diabetic CD34 < sup > + < /sup > cells
This study tested if the protective functions of Ang-(1-7) or TGFβ1-silencing are mediated by mitoTERT and that diabetes decreases FL-TERT expression by inducing splicing. CD34+ cells were isolated from the peripheral blood mononuclear cells of nondiabetic (ND, n = 68) or DB (n = 74) subjects. NO and mitoROS levels were evaluated by flow cytometry. TERT splice variants and mitoDNA-lesions were characterized by qPCR. TRAP assay was used for telomerase activity. Decoy peptide was used to block mitochondrial translocation (mitoXTERT). TERT inhibitor or mitoXTERT prevented the effects of Ang-(1-7) on NO or mitoROS levels in DB-CD34+ cells. FL-TERT expression and telomerase activity were lower and mitoDNA-lesions were higher in DB cells compared to ND and were reversed by Ang-(1-7) or TGFβ1-silencing. The prevalence of TERT splice variants, with predominant β-TERT expression, was higher and the expression of FL-TERT was lower in DB cells (n = 25) compared to ND (n = 30). Ang-(1-7) or TGFβ1-silencing decreased TERT-splicing and increased FL-TERT. Blocking of β-splicing increased FL-TERT and protected mitoDNA in DB-cells. The findings suggest that diabetes induces TERT-splicing in CD34+ cells and that β-TERT splice variant largely contributes to the mitoDNA oxidative damage.PMID:38458330 | DOI:10.1016/j.bcp.2024.116109
Source: Biochemical Pharmacology - Category: Drugs & Pharmacology Authors: Jesmin Jahan Shrinidh Joshi Ildamaris Montes de Oca Andrew Toelle Christine Lopez-Yang Carmen V Chacon Andreas W Beyer Charles A Garcia Yagna Pr Jarajapu Source Type: research