Involvement of lncRNA TUG1 in HIV-1 Tat-Induced Astrocyte Senescence.
Prakash P PillaiMuthukumar KannanSusmita SilSeema SinghAnnadurai ThangarajErnest T ChiveroRaghubendra Singh DagurAshutosh TripathiGuoku HuPalsamy PeriyasamyShilpa BuchPublished in: International journal of molecular sciences (2023)
HIV-1 infection in the era of combined antiretroviral therapy has been associated with premature aging. Among the various features of HIV-1 associated neurocognitive disorders, astrocyte senescence has been surmised as a potential cause contributing to HIV-1-induced brain aging and neurocognitive impairments. Recently, lncRNAs have also been implicated to play essential roles in the onset of cellular senescence. Herein, using human primary astrocytes (HPAs), we investigated the role of lncRNA TUG1 in HIV-1 Tat-mediated onset of astrocyte senescence. We found that HPAs exposed to HIV-1 Tat resulted in significant upregulation of lncRNA TUG1 expression that was accompanied by elevated expression of p16 and p21, respectively. Additionally, HIV-1 Tat-exposed HPAs demonstrated increased expression of senescence-associated (SA) markers-SA-β-galactosidase (SA-β-gal) activity and SA-heterochromatin foci-cell-cycle arrest, and increased production of reactive oxygen species and proinflammatory cytokines. Intriguingly, gene silencing of lncRNA TUG1 in HPAs also reversed HIV-1 Tat-induced upregulation of p21, p16, SA-β gal activity, cellular activation, and proinflammatory cytokines. Furthermore, increased expression of astrocytic p16 and p21, lncRNA TUG1, and proinflammatory cytokines were observed in the prefrontal cortices of HIV-1 transgenic rats, thereby suggesting the occurrence of senescence activation in vivo. Overall, our data indicate that HIV-1 Tat-induced astrocyte senescence involves the lncRNA TUG1 and could serve as a potential therapeutic target for dampening accelerated aging associated with HIV-1/HIV-1 proteins.
Keyphrases
- antiretroviral therapy
- hiv infected
- hiv positive
- human immunodeficiency virus
- hiv aids
- hiv testing
- hiv infected patients
- hepatitis c virus
- men who have sex with men
- endothelial cells
- poor prognosis
- high glucose
- long non coding rna
- stress induced
- reactive oxygen species
- mass spectrometry
- risk assessment
- binding protein
- electronic health record
- cell proliferation
- cell death
- high resolution
- long noncoding rna
- cerebral ischemia
- deep learning
- blood brain barrier
- brain injury
- single molecule