Role of Dysregulated Autophagy in HIV Tat, Cocaine, and cART Mediated NLRP3 Activation in Microglia

Singh, Seema; Thangaraj, Annadurai; Chivero, Ernest T.; Guo, Ming‐Lei; Periyasamy, Palsamy; Buch, Shilpa

doi:10.1007/s11481-023-10063-0

Cited by 5 publications

(5 citation statements)

References 83 publications

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“…LC3 accumulation and p62 degradation assays were performed as per standard protocols and reported previously [ 27 , 32 ]. Briefly, MIO-M1 cells were exposed to HIV-1 Tat (50 ng/mL), and four hours before harvesting, they were further treated with a saturating concentration (400 nM) of bafilomycin A1 (BAF).…”

Section: Methodsmentioning

confidence: 99%

“…Immunocytochemistry was performed as per standard protocol with minor modifications [ 26 , 27 , 28 , 29 , 30 , 32 ]. After treatment, MIO-M1 cells were briefly rinsed with 1× PBS, followed by fixation with 4% paraformaldehyde at room temperature for 20 min.…”

Section: Methodsmentioning

confidence: 99%

“…Autophagosome formation and maturation assay was performed as per standard protocol with minor modifications [ 27 , 32 ]. Briefly, MIO-M1 cells were transfected with the tandem fluorescent-tagged LC3B plasmid (ptfLC3; Addgene, Watertown, MA, USA, Cat.…”

Section: Methodsmentioning

confidence: 99%

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HIV-1 Tat-Mediated Human Müller Glial Cell Senescence Involves Endoplasmic Reticulum Stress and Dysregulated Autophagy

Deshetty,

Chatterjee,

Buch

et al. 2024

Viruses

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Antiretroviral treatments have notably extended the lives of individuals with HIV and reduced the occurrence of comorbidities, including ocular manifestations. The involvement of endoplasmic reticulum (ER) stress in HIV-1 pathogenesis raises questions about its correlation with cellular senescence or its role in initiating senescent traits. This study investigated how ER stress and dysregulated autophagy impact cellular senescence triggered by HIV-1 Tat in the MIO-M1 cell line (human Müller glial cells). Cells exposed to HIV-1 Tat exhibited increased vimentin expression combined with markers of ER stress (BiP, p-eIF2α), autophagy (LC3, Beclin-1, p62), and the senescence marker p21 compared to control cells. Western blotting and staining techniques like SA-β-gal were employed to examine these markers. Additionally, treatments with ER stress inhibitor 4-PBA before HIV-1 Tat exposure led to a decreased expression of ER stress, senescence, and autophagy markers. Conversely, pre-treatment with the autophagy inhibitor 3-MA resulted in reduced autophagy and senescence markers but did not alter ER stress markers compared to control cells. The findings suggest a link between ER stress, dysregulated autophagy, and the initiation of a senescence phenotype in MIO-M1 cells induced by HIV-1 Tat exposure.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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HIV-1 Tat-Mediated Human Müller Glial Cell Senescence Involves Endoplasmic Reticulum Stress and Dysregulated Autophagy

Deshetty,

Chatterjee,

Buch

et al. 2024

Viruses

Self Cite

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“…HIV-1 infection prompts inflammasome activation in microglia, leading to the release of IL-1β, which could contribute to inflammation and neuronal death, potentially leading to complex neurobehavioral deficits [107]. HIV Tat, cocaine, and cART can activate NLRP3 inflammasome signaling, leading to the generation of proinflammatory cytokines in microglial cells and iTat mice, potentially contributing to the dysregulated neuroinflammation observed in NeuroHIV in PWH on cART with cocaine addiction [108]. HIV-1 infection induces pro-IL-1β production in monocytes by activating TLR8 and subsequently activates caspase-1 through the NLRP3 inflammasome, leading to the cleavage of pro-IL-1β into its bioactive form, IL-1β, underscoring the essential roles of both TLR8 and NLRP3 in HIV-1-induced inflammation.…”

Section: Inflammasomes and Hivmentioning

confidence: 99%

A Perfect Storm: The Convergence of Aging, Human Immunodeficiency Virus Infection, and Inflammasome Dysregulation

Thirugnanam,

Rout

2024

CIMB

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The emergence of combination antiretroviral therapy (cART) has greatly transformed the life expectancy of people living with HIV (PWH). Today, over 76% of the individuals with HIV have access to this life-saving therapy. However, this progress has come with a new challenge: an increase in age-related non-AIDS conditions among patients with HIV. These conditions manifest earlier in PWH than in uninfected individuals, accelerating the aging process. Like PWH, the uninfected aging population experiences immunosenescence marked by an increased proinflammatory environment. This phenomenon is linked to chronic inflammation, driven in part by cellular structures called inflammasomes. Inflammatory signaling pathways activated by HIV-1 infection play a key role in inflammasome formation, suggesting a crucial link between HIV and a chronic inflammatory state. This review outlines the inflammatory processes triggered by HIV-1 infection and aging, with a focus on the inflammasomes. This review also explores current research regarding inflammasomes and potential strategies for targeting inflammasomes to mitigate inflammation. Further research on inflammasome signaling presents a unique opportunity to develop targeted interventions and innovative therapeutic modalities for combating HIV and aging-associated inflammatory processes.

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“…However, the mechanisms involved are not clear [75][76][77]. Despite this, some drugs, including cocaine [78] or other toxic substances of exogenous or endogenous nature and pathogens have been tested to evoke autophagic cell death in astrocytes and in consequent pathogenesis of neurodegeneration [79]. Recently, a close relationship between glia maturation factor (GMF), autophagy-related proteins, and the NLRP3 inflammasome and a shift of microglia from M1 to M2 in AD patients has been detected [80,81].…”

Section: Autophagymentioning

confidence: 99%

Neuroinflammation and Neurodegenerative Diseases: How Much Do We Still Not Know?

Balistreri,

Monastero

2023

Brain Sciences

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The term “neuroinflammation” defines the typical inflammatory response of the brain closely related to the onset of many neurodegenerative diseases (NDs). Neuroinflammation is well known, but its mechanisms and pathways are not entirely comprehended. Some progresses have been achieved through many efforts and research. Consequently, new cellular and molecular mechanisms, diverse and conventional, are emerging. In listing some of those that will be the subject of our description and discussion, essential are the important roles of peripheral and infiltrated monocytes and clonotypic cells, alterations in the gut–brain axis, dysregulation of the apelinergic system, alterations in the endothelial glycocalyx of the endothelial component of neuronal vascular units, variations in expression of some genes and levels of the encoding molecules by the action of microRNAs (miRNAs), or other epigenetic factors and distinctive transcriptional factors, as well as the role of autophagy, ferroptosis, sex differences, and modifications in the circadian cycle. Such mechanisms can add significantly to understanding the complex etiological puzzle of neuroinflammation and ND. In addition, they could represent biomarkers and targets of ND, which is increasing in the elderly.

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Role of Dysregulated Autophagy in HIV Tat, Cocaine, and cART Mediated NLRP3 Activation in Microglia

Cited by 5 publications

References 83 publications

HIV-1 Tat-Mediated Human Müller Glial Cell Senescence Involves Endoplasmic Reticulum Stress and Dysregulated Autophagy

HIV-1 Tat-Mediated Human Müller Glial Cell Senescence Involves Endoplasmic Reticulum Stress and Dysregulated Autophagy

A Perfect Storm: The Convergence of Aging, Human Immunodeficiency Virus Infection, and Inflammasome Dysregulation

Neuroinflammation and Neurodegenerative Diseases: How Much Do We Still Not Know?

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