PARP-1 mediated cell death is directly activated by ZIKV infection

Yang

Oxidative Medicine and Cellular Longevity

2020

Background. Chronic kidney disease (CKD) is a global health burden with high mortality and morbidity. Clinical efficacy has been demonstrated for Shen Shuai II Recipe (SSR), an approved and widely used Chinese herbal medicine for over 20 years in China, to attenuate CKD progression. In this study, we explored the underlying molecular mechanisms of SSR benefits and studied its effects on apoptosis, a critical process in CKD development and progression. CKD was induced in rats with 5/6 renal ablation and infarction (A/I). Eight weeks after SSR treatment, we mainly assessed the severity of renal injury and fibrosis, the translocation of apoptotic factors in the mitochondrial apoptosis pathway, the degree of mitochondrial dysfunction, and the nuclear and mitochondrial translocation of p53. Furthermore, we detected the interaction of p53 with antiapoptotic Bcl-xL and Bcl-2 proteins. Our results showed that SSR significantly attenuated renal injury and fibrosis and inhibited the mitochondrial accumulation of proapoptotic proteins Bax and Puma and release of cytochrome c from mitochondria to the cytosol in a rat CKD model. In addition, SSR also improved the mitochondrial function and inhibited the nuclear and mitochondrial translocation of p53. In addition, SSR suppressed the p53 transactivation and the interaction of p53 with Bcl-xL and Bcl-2. These results suggested that SSR could block apoptosis in CKD by inhibiting p53 transcriptional-dependent and transcriptional-independent proapoptotic function and the mitochondrial pathway of apoptosis.

Section: Ssr Blocked Renalmentioning

confidence: 70%

Shen Shuai II Recipe Attenuates Apoptosis in 5/6 Renal Ablation/Infarction Rats by Inhibiting p53 and the Mitochondrial Pathway of Apoptosis

Yang

Oxidative Medicine and Cellular Longevity

2020

Sig Transduct Target Ther

“…278 It can be caused by diverse virus families ranging from DNA (i.e., HBV, EBV, HSV-1) to RNA viruses (i.e., HCV, RSV, DENV, Influenza, ZIKA, HIV). [279][280][281][282][283] The increased cellular ROS by viral infection cause DNA damage, gene mutation, cell death, viral DNA integration and tumorigenesis. [284][285][286][287][288][289][290] For instance, acute phase of HCV infection induces oxidative stress via enhancing NOXs expression and activity to generate ROS generation and decreasing GSH, which supports the high rates of viral replication and apoptotic cell death.…”

Section: Abnormal Nad + Metabolism In the Pathophysiological Conditionmentioning

confidence: 99%

“…To repair the oxidative stress-induced DNA damage, a large amount of NAD + were consumed by elevated PARPs in response to virus infection, i.e., HSV-1, ZIKV and New Sindbis virus (SV). 281 , 282 , 295 Beyond the important role in DNA repair, PARP-1 also acts as a modulator of NF-κB, inducing the downstream CCL2-CCR2 signaling, which is required for the recruitment of NK cell to the infection site and viral control. 296 Therefore, PARPs have antiviral activity against multiple classes of viruses, including retroviruses, alphaviruses, filoviruses, herpesviruses, adenoviruses and coronavirus through enhancing the innate immunity.…”

Section: Abnormal Nad + Metabolism In the Pathophymentioning

confidence: 99%

NAD+ metabolism: pathophysiologic mechanisms and therapeutic potential

Xie

Zhang

Gao

et al. 2020

559

383

Nicotinamide adenine dinucleotide (NAD+) and its metabolites function as critical regulators to maintain physiologic processes, enabling the plastic cells to adapt to environmental changes including nutrient perturbation, genotoxic factors, circadian disorder, infection, inflammation and xenobiotics. These effects are mainly achieved by the driving effect of NAD+ on metabolic pathways as enzyme cofactors transferring hydrogen in oxidation-reduction reactions. Besides, multiple NAD+-dependent enzymes are involved in physiology either by post-synthesis chemical modification of DNA, RNA and proteins, or releasing second messenger cyclic ADP-ribose (cADPR) and NAADP+. Prolonged disequilibrium of NAD+ metabolism disturbs the physiological functions, resulting in diseases including metabolic diseases, cancer, aging and neurodegeneration disorder. In this review, we summarize recent advances in our understanding of the molecular mechanisms of NAD+-regulated physiological responses to stresses, the contribution of NAD+ deficiency to various diseases via manipulating cellular communication networks and the potential new avenues for therapeutic intervention.

Am J Respir Cell Mol Biol

“…Although one can speculate whether or not a PARP1 inhibitor may influence severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication or release, the fact remains that there are currently no direct studies evaluating the role of PARP1 and/or the effect of the clinically approved PARP inhibitors on SARS-CoV-2 in vitro or in vivo . Nevertheless, it should be emphasized that in several models of viral infection, PARP1 inhibitors are effective in counteracting the viral-associated cellular energetic disturbances, can exert cytoprotective effects in vitro ( 108 ).…”

Section: The Therapeutic Efficacy Of Parp Inhibitors In Alimentioning

confidence: 99%

Poly(ADP-Ribose) Polymerase Inhibition in Acute Lung Injury. A Reemerging Concept

Szabó

Martins

Liaudet

2020

PARP1, the major isoform of a family of ADP-ribosylating enzymes, has been implicated in the regulation of various biological processes including DNA repair, gene transcription, and cell death. The concept that PARP1 becomes activated in acute lung injury (ALI) and that pharmacological inhibition or genetic deletion of this enzyme can provide therapeutic benefits emerged over 20 years ago. The current article provides an overview of the cellular mechanisms involved in the pathogenetic roles of PARP1 in ALI and provides an overview of the preclinical data supporting the efficacy of PARP (poly[ADP-ribose] polymerase) inhibitors. In recent years, several ultrapotent PARP inhibitors have been approved for clinical use (for the therapy of various oncological diseases): these newly-approved PARP inhibitors were recently reported to show efficacy in animal models of ALI. These observations offer the possibility of therapeutic repurposing of these inhibitors for patients with ALI. The current article lays out a potential roadmap for such repurposing efforts. In addition, the article also overviews the scientific basis of potentially applying PARP inhibitors for the experimental therapy of viral ALI, such as coronavirus disease (COVID-19)–associated ALI.