Telomerase reverse transcriptase (TERT) is the catalytic subunit of telomerase, a ribonucleoprotein complex crucial for maintaining telomere integrity and cellular immortality. Telomeres are repetitive nucleotide sequences at the ends of chromosomes that shorten with each cell division, ultimately triggering senescence or apoptosis. TERT counteracts this shortening by adding telomeric repeat sequences to chromosome ends, thereby maintaining genomic stability. While TERT is highly active in stem cells, germ cells, and certain proliferating tissues, its expression is normally repressed in somatic cells. However, aberrant reactivation of TERT is a hallmark of cancer, leading to uncontrolled cell proliferation by conferring replicative immortality. In addition to its classic role in telomere maintenance, TERT has non-telomeric functions, including mitochondrial protection, gene expression regulation, and participation in signaling pathways, making it a multifaceted and important player in cellular homeostasis and disease pathogenesis.
TERT adenovirus refers to a genetically engineered adenoviral vector designed to deliver or regulate the TERT gene for therapeutic or research purposes. Adenoviruses are non-enveloped, double-stranded DNA viruses widely used in gene therapy due to their high transduction efficiency, broad tropism, and ability to infect both dividing and dormant cells. In cancer research, oncolytic adenoviruses targeting TERT have been developed to exploit elevated TERT activity in malignant tumors, selectively replicating in and lysing tumor cells. For example, promoters such as the human TERT (hTERT) promoter can drive viral replication exclusively in cancer cells, minimizing off-target effects. Furthermore, TERT-targeted adenoviruses are being used in regenerative medicine to enhance telomerase activity in aged or damaged tissues, potentially mitigating age-related degeneration.
Telomerase reverse transcriptase (TERT) has been reported to protect cells from ischemic injury in many diseases. However, the protective role of TERT in myocardial ischemia-reperfusion injury (MIRI) is still unclear. Here, rat myocardial H9c2 cells were subjected to oxygen and glucose deprivation (OGD) followed by reperfusion to simulate MIRI in vivo. TERT expression increased in H9c2 cells after OGD. A TERT overexpression model was constructed by adenovirus infection. After OGD, TERT overexpression promoted H9c2 cell proliferation, attenuated cell apoptosis, and enhanced autophagy. These studies suggest that TERT plays a protective role by promoting cardiomyocyte proliferation, inhibiting cell apoptosis, and enhancing autophagy after MIRI. Further studies on TERT are expected to reveal new therapeutic targets for myocardial ischemia-reperfusion injury.
Cultured myocardial cells (H9c2) were divided into 4 groups: normoxia control group (CON), cells treated with oxygen and glucose deprivation (OGD), cells infected with empty vector adenovirus and treated with OGD (OGD + EMPTY), cells infected with TERT overexpression adenovirus and treated by OGD (OGD + TERT). Western blotting was used to detect the expression of TERT in cardiomyocytes of each group 48 h after OGD. The expression levels of TERT in OGD and OGD + EMPTY groups were significantly higher than those in CON group (Figure 1), indicating that ischemia-reperfusion injury induced the expression of TERT in cardiomyocytes. Moreover, the expression of TERT in the OGD + TERT group was further significantly higher than that in the OGD and OGD + EMPTY groups (Figure 1). There was no significant difference in the expression levels of TERT between the OGD group and the OGD + EMPTY group (Figure 1). This demonstrated that the expression of TERT in myocardial cells was enhanced by infection with TERT overexpression adenovirus after OGD.
Figure 1. Expression of TERT in H9c2 cells. (Fang Z, et al., 2020.)
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The TERT adenovirus effectively extended replicative lifespan in our primary cells. The virus was high-titer and ready-to-use, saving us weeks of optimization.
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