Low-dose nicotine promotes autophagy of cardiomyocytes by upregulating HO-1 expression

Xing, Ruinan; Cheng, Xiaoli; Qi, Yanping; Tian, Xiaoxiang; Yan, Chunhong; Liu, Dan; Han, Yaling

doi:10.1016/j.bbrc.2019.11.086

Cited by 13 publications

(8 citation statements)

References 28 publications

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“…As previously illustrated, NIC directly induces podocyte and renal proximal tubule cell apoptosis [ 27 , 28 ]; it also indirectly induces apoptotic cell death via oxidative stress [ 29 ] or activation of TGF-β1 [ 22 ]. NIC may also induce autophagy in pancreatic stellate cells [ 30 ], neonatal mouse cardiac myocytes [ 31 ], and vascular smooth muscle cells [ 32 ]. Thus, oxidative stress and programmed cell death are interrelated.…”

Section: Discussionmentioning

confidence: 99%

Nicotine exacerbates tacrolimus-induced renal injury by programmed cell death

Jiang

Sheng

Luo

et al. 2021

Korean J Intern Med

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Background/Aims: Cigarette smoking is an important modifiable risk factor in kidney disease progression. However, the underlying mechanisms for this are lacking. This study aimed to assess whether nicotine (NIC), a major toxic component of cigarette smoking, would exacerbates tacrolimus (TAC)-induced renal injury.Methods: Sprague-Dawley rats were treated daily with NIC, TAC, or both drugs for 4 weeks. The influence of NIC on TAC-caused renal injury was examined via renal function, histopathology, oxidative stress, mitochondria, endoplasmic reticulum (ER) stress, and programmed cell death (apoptosis and autophagy).Results: Both NIC and TAC significantly impaired renal function and histopathology, while combined NIC and TAC treatment aggravated these parameters beyond the effects of either alone. Increased oxidative stress, ER stress, mitochondrial dysfunction, proinf lammatory and profibrotic cytokine expressions, and programmed cell death from either NIC or TAC were also aggravated by the two combined.Conclusions: Our observations suggest that NIC exacerbates chronic TAC nephrotoxicity, implying that smoking cessation may be beneficial for transplant smokers taking TAC.

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Section: Discussionmentioning

confidence: 99%

Nicotine exacerbates tacrolimus-induced renal injury by programmed cell death

Jiang

Sheng

Luo

et al. 2021

Korean J Intern Med

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“…38 Of note, nicotine has been shown to induce autophagy in several tissues outside of the brain, although the effects of this range from beneficial to harmful depending on the tissue. [39][40][41][42][43][44][45][46] Here we found that nicotine treatment rescued impaired autophagic flux in α-synuclein flies and that this rescue was dependent on the intact expression of SV2C (Figs. 4 and 5).…”

Section: Discussionmentioning

confidence: 57%

Nicotine‐Mediated Rescue of α‐Synuclein Toxicity Requires Synaptic Vesicle Glycoprotein 2 in Drosophila

2022

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Background Parkinson's disease (PD) is characterized by α‐synuclein aggregation and loss of dopamine neurons. Risk of PD arises due to a combination of genetic and environmental factors, which may interact, termed gene–environment (G×E) interactions. An inverse association between smoking and the risk of PD is well established, and a previous genome‐wide G×E interaction study identified genetic variation in the synaptic‐vesicle glycoprotein 2C (SV2C) locus as an important mediator of the degree to which smoking is inversely associated with PD. Objective We sought to determine the mechanism of the smoking–SV2C interaction in a Drosophila model of PD. Methods Flies expressing human α‐synuclein in all neurons develop the hallmarks of PD, including motor dysfunction, loss of dopaminergic (DA) neurons, and formation of α‐synuclein inclusions. We assessed the effects of increasing doses of nicotine on these parameters of neurodegeneration, in the presence or absence of knockdown of two Drosophila orthologues of SV2, hereafter referred to as SV2L1 and SV2L2. Results The α‐synuclein–expressing flies treated with nicotine had improved locomotion, DA neuron counts, and α‐synuclein aggregation. However, in α‐synuclein–expressing flies in which SV2L1 and SV2L2 were knocked down, nicotine failed to rescue neurodegeneration. Conclusions This work confirms a G×E interaction between nicotine and SV2, defines a role for this interaction in α‐synuclein proteostasis, and suggests that future clinical trials on nicotine should consider genetic variation in SV2C. Furthermore, this provides proof of concept that our model can be used for the mechanistic study of G×E, paving the way for the investigation of additional G×E interactions or the identification of novel G×E. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

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“…Alterations in the lysosomal autophagy system increase α-synuclein accumulation, and excessive and/or abnormal α-synuclein then further impedes the lysosomal autophagy system in a vicious cycle 35 . Of note, nicotine has been shown to induce autophagy in several tissues outside of the brain, though the effects of this range from beneficial to harmful depending on the tissue [36][37][38][39][40][41][42][43] . Here we found that nicotine treatment rescued impaired autophagic flux in α-synuclein flies, and that this rescue was dependent on intact expression of SV2C (Figure 6-7).…”

Section: Discussionmentioning

confidence: 99%

Nicotine-mediated rescue of α-synuclein toxicity requires synaptic vesicle glycoprotein 2

Olsen

Clemens

Feany

2022

Preprint

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Background: Parkinson's disease (PD) is characterized by alpha-synuclein aggregation and loss of dopamine (DA) neurons in the substantia nigra. Risk of PD arises due to a combination of genetic and environmental factors, which may interact, termed gene-environment (GxE) interactions. An inverse association between smoking and risk of PD is well-established, and a previous genome-wide GxE interaction study identified genetic variation in the synaptic-vesicle glycoprotein 2C (SV2C) locus as an important mediator of the degree to which smoking is inversely associated with PD. Objective: We sought to determine the mechanism of the smoking-SV2C interaction in a Drosophila model of PD. Methods: Flies expressing human alpha-synuclein in all neurons develop the hallmarks of PD, including motor dysfunction, loss of DA neurons, and formation of alpha-synuclein inclusions. We assessed the effects of increasing doses of nicotine on these parameters of neurodegeneration, in the presence or absence of SV2 knockdown. Results: alpha-synuclein-expressing flies treated with nicotine had improvement in locomotion, DA neuron counts, and in alpha-synuclein aggregation. However, in alpha-synuclein-expressing flies in which Drosophila orthologs of SV2 were knocked down, nicotine failed to rescue neurodegeneration. Conclusions: This work confirms a GxE interaction between nicotine and SV2, defines a role for this interaction in alpha-synuclein proteostasis, and suggests that future clinical trials on nicotine should consider genetic variation in SV2C. Further, this provides proof of concept that our model can be used for mechanistic study of GxE, paving the way for investigation of additional GxE interactions or identification of novel GxE.

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Low-dose nicotine promotes autophagy of cardiomyocytes by upregulating HO-1 expression

Cited by 13 publications

References 28 publications

Nicotine exacerbates tacrolimus-induced renal injury by programmed cell death

Nicotine exacerbates tacrolimus-induced renal injury by programmed cell death

Nicotine‐Mediated Rescue of α‐Synuclein Toxicity Requires Synaptic Vesicle Glycoprotein 2 in Drosophila

Nicotine-mediated rescue of α-synuclein toxicity requires synaptic vesicle glycoprotein 2

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