Dataset Information

Chandipura Virus Induced Neuronal Apoptosis via Calcium Signaling Mediated Oxidative Stress.

ABSTRACT: Chandipura Virus (CHPV) a negative-stranded RNA virus belonging to the Rhabdoviridae family, has been previously reported to bring about neuronal apoptosis by stimulating oxidative stress. Our in silico data suggested the involvement of Angiotensin II in intracellular Ca²⁺ secretion within CHPV infected cells that further lead to enhancement of ROS level and mitochondrial dysfunction. ROS is also known to phosphorylate p38 that leads to neuronal apoptosis through FasL-FADD pathway during CHPV infection. Minocycline a broad-spectrum antibiotic well-known for its anti-oxidative and anti-inflammatory role was used in the present study to investigate its efficacy against CHPV. The results obtained from the present study showed minocycline to be effective in mitigating the levels of cytoplasmic Ca²⁺, ROS, phosphorylation of p38 molecules and hence cellular apoptosis. Thus minocycline apart from being an anti-inflammatory and anti-oxidative agent, our study showed that minocycline has an additional Ca²⁺ chelation activity.

SUBMITTER: Verma AK

PROVIDER: S-EPMC6043780 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Chandipura Virus Induced Neuronal Apoptosis via Calcium Signaling Mediated Oxidative Stress.

Verma Abhishek K AK Ghosh Sourish S Basu Anirban A

Frontiers in microbiology 20180706

Chandipura Virus (CHPV) a negative-stranded RNA virus belonging to the Rhabdoviridae family, has been previously reported to bring about neuronal apoptosis by stimulating oxidative stress. Our in silico data suggested the involvement of Angiotensin II in intracellular Ca2+ secretion within CHPV infected cells that further lead to enhancement of ROS level and mitochondrial dysfunction. ROS is also known to phosphorylate p38 that leads to neuronal apoptosis through FasL-FA ...[more]

PMID: 30034380

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Project description:HIV-1 glycoprotein 120 (gp120) is known to cause neurotoxicity via several mechanisms including production of proinflammatory cytokines/chemokines and oxidative stress. Likewise, drug abuse is thought to have a direct impact on the pathology of HIV-associated neuroinflammation through the induction of proinflammatory cytokines/chemokines and oxidative stress. In the present study, we demonstrate that gp120 and methamphetamine (MA) causes apoptotic cell death by inducing oxidative stress through the cytochrome P450 (CYP) and NADPH oxidase (NOX) pathways. The results showed that both MA and gp120 induced reactive oxygen species (ROS) production in concentration- and time-dependent manners. The combination of gp120 and MA also induced CYP2E1 expression at both mRNA (1.7±0.2- and 2.8±0.3-fold in SVGA and primary astrocytes, respectively) and protein (1.3±0.1-fold in SVGA and 1.4±0.03-fold in primary astrocytes) levels, suggesting the involvement of CYP2E1 in ROS production. This was further confirmed by using a selective inhibitor of CYP2E1, diallylsulfide (DAS), and CYP2E1 knockdown using siRNA, which significantly reduced ROS production (30-60%). As the CYP pathway is known to be coupled with the NOX pathway, including Fenton-Weiss-Haber (FWH) reaction, we examined whether the NOX pathway is also involved in ROS production induced by either gp120 or MA. Our results showed that selective inhibitors of NOX, diphenyleneiodonium (DPI), and FWH reaction, deferoxamine (DFO), also significantly reduced ROS production. These findings were further confirmed using specific siRNAs against NOX2 and NOX4 (NADPH oxidase family). We then showed that gp120 and MA both induced apoptosis (caspase-3 activity and DNA lesion using TUNEL (terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling) assay) and cell death. Furthermore, we showed that DAS, DPI, and DFO completely abolished apoptosis and cell death, suggesting the involvement of CYP and NOX pathways in ROS-mediated apoptotic cell death. In conclusion, this is the first report on the involvement of CYP and NOX pathways in gp120/MA-induced oxidative stress and apoptotic cell death in astrocytes, which has clinical implications in neurodegenerative diseases, including neuroAIDS.

Dataset Information

Chandipura Virus Induced Neuronal Apoptosis via Calcium Signaling Mediated Oxidative Stress.

Publications

Chandipura Virus Induced Neuronal Apoptosis via Calcium Signaling Mediated Oxidative Stress.

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