Cocaine use may induce telomere shortening in individuals with HIV infection

Lai, Shenghan; Heaphy, Christopher M.; Rizzo, Anthony; Celentano, David D.; Gerstenblith, Gary; Li, Ji; Moore, Richard D.; Treisman, Glenn J.; Chen, Shaoguang; Foster, Parker; Kickler, Thomas S.; Li, Hong

doi:10.1016/j.pnpbp.2018.01.015

Cited by 7 publications

(7 citation statements)

References 37 publications

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“…Yang et al reported that drug abusers overall had reduced LTL, but when they classified the drugs of abuse into depressant drugs, stimulant drugs, and hallucinogenic drugs they found those taking stimulant drugs (such as METH and methylenedioxymethamphetamine [MDMA]) did not exhibit shorter LTLs [30]. In contrast, reports in cocaine users demonstrated that cocaine use promotes the shortening of telomere length [31,32]. Furthermore, cocaine abusers reporting a history of childhood abuse and neglect displayed significantly shorter telomeres than those without such history [32], suggesting adverse childhood experiences (ACEs) might contribute to the shortening of LTL in drug abusers.…”

Section: Introductionmentioning

confidence: 99%

Shortened leukocyte telomere length in young adults who use methamphetamine

et al. 2021

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Methamphetamine (METH) use, most prevalent in young adults, has been associated with high rates of morbidity and mortality. The relationship between METH use and accelerated biological aging, which can be measured using leukocyte telomere length (LTL), remains unclear. We examined whether young adult METH users have shorter LTL and explored the relationship between characteristics of METH use and LTL by using Mendelian randomization (MR) analysis. We compared the LTL for 187 METH users and 159 healthy individuals aged between 25 and 34 years and examined the relationship of LTL with METH use variables (onset age, duration, and maximum frequency of METH use) by using regression analyses. In addition, 2-stage-least-squares (2SLS) MR was also performed to possibly avoid uncontrolled confounding between characteristics of METH use and LTL. We found METH users had significantly shorter LTL compared to controls. Multivariate regression analysis showed METH use was negatively associated with LTL (β = −0.36, P < .001). Among METH users, duration of METH use was negatively associated with LTL after adjustment (β = −0.002, P = .01). We identified a single nucleotide polymorphism (SNP) rs6585206 genome-wide associated with duration of METH use. This SNP was used as an instrumental variable to avoid uncontrolled confounding for the relationship between the use duration and LTL shortening. In conclusion, we show that young adult METH users may have shorter LTL compared with controls and longer duration of METH use was significantly associated with telomere shortening. These observations suggest that METH use may accelerate biological senescence.

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Section: Introductionmentioning

confidence: 99%

Shortened leukocyte telomere length in young adults who use methamphetamine

et al. 2021

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“…S-acylated Rif1 mediated by palmitoyl acyltransferase Pfa4 mounts a localized DNAdamage response proximal to the inner nuclear membrane and promotes telomere homeostasis [59]. Longitudinal analyses of 147 HIV-infected participants in Baltimore between June 2010 and December 2016 suggested that cocaine use induced/accelerated telomere shortening in HIV-infected individuals [60]. Then, local anesthetics may also mediate the telomere homeostasis of cancer stem cells through ZDHHC15 or palmitoylation modification.…”

Section: Discussionmentioning

confidence: 99%

Local anesthetics impair the growth and self-renewal of glioblastoma stem cells by inhibiting ZDHHC15-mediated GP130 palmitoylation

et al. 2021

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Background A large number of preclinical studies have shown that local anesthetics have a direct inhibitory effect on tumor biological activities, including cell survival, proliferation, migration, and invasion. There are few studies on the role of local anesthetics in cancer stem cells. This study aimed to determine the possible role of local anesthetics in glioblastoma stem cell (GSC) self-renewal and the underlying molecular mechanisms. Methods The effects of local anesthetics in GSCs were investigated through in vitro and in vivo assays (i.e., Cell Counting Kit 8, spheroidal formation assay, double immunofluorescence, western blot, and xenograft model). The acyl-biotin exchange method (ABE) assay was identified proteins that are S-acylated by zinc finger Asp-His-His-Cys-type palmitoyltransferase 15 (ZDHHC15). Western blot, co-immunoprecipitation, and liquid chromatograph mass spectrometer-mass spectrometry assays were used to explore the mechanisms of ZDHHC15 in effects of local anesthetics in GSCs. Results In this study, we identified a novel mechanism through which local anesthetics can damage the malignant phenotype of glioma. We found that local anesthetics prilocaine, lidocaine, procaine, and ropivacaine can impair the survival and self-renewal of GSCs, especially the classic glioblastoma subtype. These findings suggest that local anesthetics may weaken ZDHHC15 transcripts and decrease GP130 palmitoylation levels and membrane localization, thus inhibiting the activation of IL-6/STAT3 signaling. Conclusions In conclusion, our work emphasizes that ZDHHC15 is a candidate therapeutic target, and local anesthetics are potential therapeutic options for glioblastoma.

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“…We observed that shorter LTLs in HIV + individuals were strongly associated with advancing age, cART without INSTI, failure to achieve viral control after initiation of cART, and substance use. In previous reports, cART and substance abuse have sometimes been associated with LTL shortening in HIV + individuals [25, 26]. Antiretroviral drug-induced toxicity is an important complication of cART, particularly for regimens containing protease inhibitors (PIs).…”

Section: Discussionmentioning

confidence: 99%

Correlates of telomere length shortening in peripheral leukocytes of HIV-infected individuals and association with leukoaraiosis

2019

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Telomere length (TL) is a marker of cellular and biological aging. Human immunodeficiency virus (HIV) infection has been reported to be associated with short TLs, which suggests that accelerated biological aging occurs in some cellular compartments of HIV + individuals. In this study, we measured the TLs of peripheral leukocytes of HIV + and healthy individuals and examined the biological and environmental correlates of TL. We also investigated the influence of TL on leukoaraiosis, an indicator of cerebral small vessel disease, in HIV + individuals. Three hundred and twenty-five HIV + individuals who received stable combination antiretroviral therapy (cART) for >1 year and achieved viral loads of <40 RNA copies/mL were enrolled along with 147 healthy individuals. Relative TLs of leukocytes were estimated by quantitative real-time polymerase chain reaction. Leukoaraiosis was assessed in 184 HIV + individuals by fluid-attenuated inversion recovery magnetic resonance imaging. We analyzed several covariates, including markers of HIV infection, cART, and social/environmental factors; variables associated with TL length in univariate analyses were incorporated into multivariate models. The TLs of peripheral leukocytes of HIV + individuals were significantly shorter than those of healthy individuals, and the rate of LT length decline with increasing age was greater. Linear regression analysis showed that in HIV + individuals, increasing age, cART without integrase-stand transfer inhibitors (INSTI), failure to achieve viral loads of <40 copies/mL within 1 year of initiating cART, and substance use were significantly associated with shorter TLs, even after adjustment for the effects of age. Logistic regression analysis indicated an increasing risk of leukoaraiosis was associated with older age, shorter TLs, hypertension, and carotid artery plaque. Multivariate regression analysis indicated that older age and shorter TLs were significant risk factors for leukoaraiosis. In summary, our data showed that TL shortening in HIV + individuals was independently associated with leukoaraiosis, and was associated with age, control of viral loads, use of INSTI, and substance use. Our results suggest that effective viral control and less toxic cART can help reduce TL shortening and improve outcomes among HIV + individuals.

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Cocaine use may induce telomere shortening in individuals with HIV infection

Abstract: Our findings suggest that cocaine use may promote premature aging in HIV-infected individuals who are on ART. Our results emphasize the importance of cocaine abstinence/reduced use, which may retard HIV-associated premature aging.

Cited by 7 publications

References 37 publications

Shortened leukocyte telomere length in young adults who use methamphetamine

Shortened leukocyte telomere length in young adults who use methamphetamine

Local anesthetics impair the growth and self-renewal of glioblastoma stem cells by inhibiting ZDHHC15-mediated GP130 palmitoylation

Correlates of telomere length shortening in peripheral leukocytes of HIV-infected individuals and association with leukoaraiosis

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