Regional Variations of Antioxidant Capacity and Oxidative Stress Responses in HIV-1 Transgenic Rats With and Without Methamphetamine Administration

Pang, Xiaosha; Panee, Jun; Liu, Xiangqian; Berry, Marla J.; Chang, Sulie L.; Chang, Linda

doi:10.1007/s11481-013-9454-8

Cited by 22 publications

(29 citation statements)

References 61 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[76][77][78] Consistent with this notion, HIV-1 proteins gp120, Tat and Vpr are known to induce ROS. [79][80][81] In conclusion, our results indicate that cells infected with latent HIV-1 show affected DNA damage response and have increased susceptibility to different agents inducing damage in DNA and to agents targeting the DDR.…”

Section: Discussionmentioning

confidence: 83%

Deficiency in DNA damage response, a new characteristic of cells infected with latent HIV-1

et al. 2017

View full text Add to dashboard Cite

Viruses can interact with host cell molecules responsible for the recognition and repair of DNA lesions, resulting in dysfunctional DNA damage response (DDR). Cells with inefficient DDR are more vulnerable to therapeutic approaches that target DDR, thereby raising DNA damage to a threshold that triggers apoptosis. Here, we demonstrate that 2 Jurkat-derived cell lines with incorporated silent HIV-1 provirus show increases in DDR signaling that responds to formation of double strand DNA breaks (DSBs). We found that phosphorylation of histone H2AX on Ser139 (gamma-H2AX), a biomarker of DSBs, and phosphorylation of ATM at Ser1981, Chk2 at Thr68, and p53 at Ser15, part of signaling pathways associated with DSBs, are elevated in these cells. These results indicate a DDR defect even though the virus is latent. DDR-inducing agents, specifically high doses of nucleoside RT inhibitors (NRTIs), caused greater increases in gamma-H2AX levels in latently infected cells. Additionally, latently infected cells are more susceptible to long-term exposure to G-quadruplex stabilizing agents, and this effect is enhanced when the agent is combined with an inhibitor targeting DNA-PK, which is crucial for DSB repair and telomere maintenance. Moreover, exposing these cells to the cancer drug etoposide resulted in formation of DSBs at a higher rate than in un-infected cells. Similar effects of etoposide were also observed in population of primary memory T cells infected with latent HIV-1. Sensitivity to these agents highlights a unique vulnerability of latently infected cells, a new feature that could potentially be used in developing therapies to eliminate HIV-1 reservoirs.

show abstract

Section: Discussionmentioning

confidence: 83%

Deficiency in DNA damage response, a new characteristic of cells infected with latent HIV-1

et al. 2017

View full text Add to dashboard Cite

show abstract

“…Indeed, HIV-1 Tg animals are particularly vulnerable to a variety of drugs of abuse including methamphet-amine (Pang et al 2013; Moran et al 2012), nicotine (Vigorito et al 2013) and ethanol (Sakar and Chang 2013), suggesting a commonality of neuropathological impairment across many different drug classes. It is possible that MSNs might be a common neuropathological link in altered responses of the HIV-1 Tg animals to drugs of abuse, as alterations in MSN spines have been found following cocaine/amphetamine exposure (Shen et al 2014; Dumitriu et al 2012) nicotine exposure (Gipson et al 2013) and alcohol (Gass and Olive 2012).…”

Section: Discussionmentioning

confidence: 99%

HIV-1 Transgenic Female Rat: Synaptodendritic Alterations of Medium Spiny Neurons in the Nucleus Accumbens

Roscoe

Mactutus

Booze

2014

J Neuroimmune Pharmacol

View full text Add to dashboard Cite

HIV-1 associated neurocognitive deficits are increasing in prevalence, although the neuronal basis for these deficits is unclear. HIV-1 Tg rats constitutively express 7 of 9 HIV-associated proteins, and may be useful for studying the neuropathological substrates of HIV-1 associated neurocognitive disorders (HAND). In this study, adult female HIV-1 Tg rats and F344 control rats had similar growth rates, estrous cyclicity and startle reflex inhibition to a visual prepulse stimulus. Medium spiny neurons (MSNs) in the nucleus accumbens (NAcc) were ballistically-labeled utilizing the indocarbocyanine dye DiI. The branching complexity of MSNs in the NAcc was significantly decreased in HIV-1 Tg rats, relative to controls; moreover, the shorter length and decreased volume of dendritic spines, but unchanged head diameter, in HIV-1 Tg rats suggested a reduction of longer spines and an increase in shorter, less projected spines, indicating a population shift to a more immature spine phenotype. Collectively, these results from HIV-1 Tg female rats indicated significant synaptodendritic alterations of MSNs in the NAcc occur as a consequence of chronic, low-level, exposure to HIV-1 associated proteins.

show abstract

“…HIV and opiate neurotoxicity frequently show regional specificity in the brain (Fitting et al, 2010b; Pang et al, 2013). This is partly due to variability in expression of receptors important for HIV binding and entry, as well as opiate receptors (Arvidsson et al, 1995; Berger and Arendt, 2000; Berger and Nath, 1997; Mansour et al, 1995; Mansour et al, 1988; Nath, 2014; Podhaizer et al, 2012; Stiene-Martin et al, 1998; Turchan-Cholewo et al, 2008).…”

Section: Discussionmentioning

confidence: 99%

GSK3β-activation is a point of convergence for HIV-1 and opiate-mediated interactive neurotoxicity

Masvekar

El‐Hage

Hauser

et al. 2015

Molecular and Cellular Neuroscience

View full text Add to dashboard Cite

Infection of the CNS with HIV-1 occurs rapidly after primary peripheral infection. HIV-1 can induce a wide range of neurological deficits, collectively known as HIV-1-associated neurocognitive disorders. Our previous work has shown that the selected neurotoxic effects induced by individual viral proteins, Tat and gp120, and by HIV+ supernatant are enhanced by co-exposure to morphine. This mimics co-morbid neurological effects observed in opiate-abusing HIV+ patients. Although there is a correlation between opiate drug abuse and progression of HIV-1-associated neurocognitive disorders, the mechanisms underlie interactions between HIV-1 and opiates remain obscure. Previous studies have shown that HIV-1 induces neurotoxic effects through abnormal activation of GSK3β. Interestingly, expression of GSK3β has shown to be elevated in brains of young opiate abusers indicating that GSK3β is also linked to neuropathology seen with opiate abusing patients. Thus, we hypothesize that GSK3β activation is a point of convergence for HIV- and opiate-mediated interactive neurotoxic effects. Neuronal cultures were treated with supernatant from HIV-1SF162-infected THP-1 cells, in the presence or absence of morphine and GSK3β inhibitors. Our results show that GSK3β inhibitors, including valproate and small molecule inhibitors, significantly reduce HIV-1-mediated neurotoxic outcomes, and also negate interactions with morphine that result in cell death, suggesting that GSK3β-activation is an important point of convergence and a potential therapeutic target for HIV- and opiate-mediated neurocognitive deficits.

show abstract

Regional Variations of Antioxidant Capacity and Oxidative Stress Responses in HIV-1 Transgenic Rats With and Without Methamphetamine Administration

Cited by 22 publications

References 61 publications

Deficiency in DNA damage response, a new characteristic of cells infected with latent HIV-1

Deficiency in DNA damage response, a new characteristic of cells infected with latent HIV-1

HIV-1 Transgenic Female Rat: Synaptodendritic Alterations of Medium Spiny Neurons in the Nucleus Accumbens

GSK3β-activation is a point of convergence for HIV-1 and opiate-mediated interactive neurotoxicity

Contact Info

Product

Resources

About