Endoplasmic reticulum stress leads to mitochondria-mediated apoptosis in cells treated with anti-HIV protease inhibitor ritonavir

Ganta, Krishna Kumar; Chaubey, Binay

doi:10.1007/s10565-018-09451-7

Cited by 28 publications

(23 citation statements)

References 48 publications

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“…CHOP is proapoptotic in cell apoptosis and increases rapidly under ER stress (Guan et al, 2019;Yang et al, 2019b). As a molecular chaperone, GRP78 regulates protein folding in the ER (Ganta and Chaubey, 2019) is suggested to be antiapoptotic during ER stress (Yang et al, 2018;Ardic et al, 2019). Interestingly, GRP78 expression was inhibited in our study.…”

Section: Discussionmentioning

confidence: 49%

Patchouli Alcohol Improves the Integrity of the Blood-Spinal Cord Barrier by Inhibiting Endoplasmic Reticulum Stress Through the Akt/CHOP/Caspase-3 Pathway Following Spinal Cord Injury

Huang

Zhang

Chu

et al. 2021

Front. Cell Dev. Biol.

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Spinal cord injury (SCI) is a destructive and complex disorder of the central nervous system (CNS) for which there is no clinical treatment. Blood-spinal cord barrier (BSCB) rupture is a critical event in SCI that aggravates nerve injury. Therefore, maintaining the integrity of the BSCB may be a potential method to treat SCI. Here, we showed that patchouli alcohol (PA) exerts protective effects against SCI. We discovered that PA significantly prevented hyperpermeability of the BSCB by reducing the loss of tight junctions (TJs) and endothelial cells. PA also suppressed endoplasmic reticulum stress and apoptosis in vitro. Furthermore, in a rat model of SCI, PA effectively improved neurological deficits. Overall, these results prove that PA exerts neuroprotective effects by maintaining BSCB integrity and thus be a promising candidate for SCI treatment.

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Section: Discussionmentioning

confidence: 49%

Patchouli Alcohol Improves the Integrity of the Blood-Spinal Cord Barrier by Inhibiting Endoplasmic Reticulum Stress Through the Akt/CHOP/Caspase-3 Pathway Following Spinal Cord Injury

Huang

Zhang

Chu

et al. 2021

Front. Cell Dev. Biol.

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“…Concurrently, the drug's entry into mitochondria diminished ∆Ψ m . Both outer and inner mitochondrial membrane damage lead to a release of cytochrome c, which executes mitochondria-mediated apoptosis by activating caspase 9; this activates caspase 7, which performs cleavage of PARP-1 (Figure 2) [98]. In another study, rats treated with RTV exhibited hepatotoxicity due to increased transaminases and oxidative stress, with a reduction of GSH levels and enhanced ROS and NO production [99].…”

Section: Pismentioning

confidence: 99%

“…Some studies with different human hepatocyte cell lines (L-02, HepaRG and Huh-7.5) have shown that RTV exerts an anti-proliferative effect [97,98]. Moreover, it can induce apoptosis in hepatocytes via the caspase-cascade system by enhancing caspase 3 cleavage [97].…”

Section: Pismentioning

confidence: 99%

“…Moreover, it can induce apoptosis in hepatocytes via the caspase-cascade system by enhancing caspase 3 cleavage [97]. The mechanism suggested for RTV-induced cytotoxicity linked ER stress with mitochondria-mediated apoptosis [98]; namely, in Huh-7.5 cells, treatment with RTV enhanced the expression of the ER stress mediator BiP, linked in turn to Bax relocation at the mitochondrial outer membrane, which caused MMP. Concurrently, the drug's entry into mitochondria diminished ∆Ψ m .…”

Section: Pismentioning

confidence: 99%

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Apoptosis of Hepatocytes: Relevance for HIV-Infected Patients under Treatment

Gruevska

Moragrega

Cossarizza

et al. 2021

Cells

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Due to medical advances over the past few decades, human immunodeficiency virus (HIV) infection, once a devastatingly mortal pandemic, has become a manageable chronic condition. However, available antiretroviral treatments (cART) cannot fully restore immune health and, consequently, a number of inflammation-associated and/or immunodeficiency complications have manifested themselves in treated HIV-infected patients. Among these chronic, non-AIDS (acquired immune deficiency syndrome)-related conditions, liver disease is one of the deadliest, proving to be fatal for 15–17% of these individuals. Aside from the presence of liver-related comorbidities, including metabolic disturbances and co-infections, HIV itself and the adverse effects of cART are the main factors that contribute to hepatic cell injury, inflammation, and fibrosis. Among the molecular mechanisms that are activated in the liver during HIV infection, apoptotic cell death of hepatocytes stands out as a key pathogenic player. In this review, we will discuss the evidence and potential mechanisms involved in the apoptosis of hepatocytes induced by HIV, HIV-encoded proteins, or cART. Some antiretroviral drugs, especially the older generation, can induce apoptosis of hepatic cells, which occurs through a variety of mechanisms, such as mitochondrial dysfunction, increased production of reactive oxygen species (ROS), and induction of endoplasmic reticulum (ER) stress and unfolded protein response (UPR), all of which ultimately lead to caspase activation and cell death.

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“…As a consequence of the decrease of MCN, the cellular oxidative phosphorylation is disturbed, which leads to increased production of reactive oxygen species (ROS) that in turn may generate mtDNA point mutations and/or deleted mtDNA (MDD) [ 32 , 34 ]. Recent in vitro studies showed that most of the protease inhibitors (PIs) can induce mitochondrial-induced apoptosis [ 35 , 36 , 37 ] and increase ROS production [ 36 , 37 , 38 , 39 , 40 ]. These two mechanisms can lead to a decrease of mtDNA content and induce mtDNA mutations, as NRTIs do.…”

Section: Introductionmentioning

confidence: 99%

Mitochondrial DNA Parameters in Blood of Infants Receiving Lopinavir/Ritonavir or Lamivudine Prophylaxis to Prevent Breastfeeding Transmission of HIV-1

Monnin

Nagot

Peries

et al. 2020

JCM

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Children who are human immunodeficiency virus (HIV)-exposed but uninfected (CHEU) accumulate maternal HIV and antiretroviral exposures through pregnancy, postnatal prophylaxis, and breastfeeding. Here, we compared the dynamics of mitochondrial DNA (mtDNA) parameters in African breastfed CHEU receiving lopinavir/ritonavir (LPV/r) or lamivudine (3TC) pre-exposure prophylaxis during the first year of life. The number of mtDNA copies per cell (MCN) and the proportion of deleted mtDNA (MDD) were assessed at day 7 and at week 50 post-delivery (PrEP group). mtDNA depletion was defined as a 50% or more decrease from the initial value, and mtDNA deletions was the detection of mtDNA molecules with large DNA fragment loss. We also performed a sub-analysis with CHEU who did not receive a prophylactic treatment in South Africa (control group). From day seven to week 50, MCN decreased with a median of 41.7% (interquartile range, IQR: 12.1; 64.4) in the PrEP group. The proportion of children with mtDNA depletion was not significantly different between the two prophylactic regimens. Poisson regressions showed that LPV/r and 3TC were associated with mtDNA depletion (reference: control group; LPV/r: PR = 1.75 (CI95%: 1.15–2.68), p < 0.01; 3TC: PR = 1.54 (CI95%: 1.00–2.37), p = 0.05). Moreover, the proportion of children with MDD was unexpectedly high before randomisation in both groups. Long-term health impacts of these mitochondrial DNA parameters should be investigated further for both CHEU and HIV-infected children receiving LPV/r- or 3TC- based regimens.

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Endoplasmic reticulum stress leads to mitochondria-mediated apoptosis in cells treated with anti-HIV protease inhibitor ritonavir

Cited by 28 publications

References 48 publications

Patchouli Alcohol Improves the Integrity of the Blood-Spinal Cord Barrier by Inhibiting Endoplasmic Reticulum Stress Through the Akt/CHOP/Caspase-3 Pathway Following Spinal Cord Injury

Patchouli Alcohol Improves the Integrity of the Blood-Spinal Cord Barrier by Inhibiting Endoplasmic Reticulum Stress Through the Akt/CHOP/Caspase-3 Pathway Following Spinal Cord Injury

Apoptosis of Hepatocytes: Relevance for HIV-Infected Patients under Treatment

Mitochondrial DNA Parameters in Blood of Infants Receiving Lopinavir/Ritonavir or Lamivudine Prophylaxis to Prevent Breastfeeding Transmission of HIV-1

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