Enoxacin extends lifespan of C. elegans by inhibiting miR-34-5p and promoting mitohormesis

Pinto, Silas; Sato, Vitor; De-Souza, Evandro A.; Ferraz, Rafael C.; Camara, Henrique; Pinca, Ana Paula F.; Mazzotti, Diego R.; Lovci, Michael T.; Tonon, Guilherme; Lopes‐Ramos, Camila M.; Parmigiani, Raphael B.; Würtele, Martin; Massirer, Katlin B.; Mori, Marcelo A.

doi:10.1016/j.redox.2018.06.006

Cited by 43 publications

(30 citation statements)

References 55 publications

(85 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“… 74 This mitochondrial ROS may in turn trigger an autophagic response via inhibition of mTORC1 ( Figure 2 ). 75 - 78 Furthermore, various repurposed approved drugs have been found to increase life span and health span in rotifers ( Table 1 ). 71 Similarly, physical exercise may counteract aging by virtue of a hormetic dose–response relationship.…”

Section: Role Of Autophagy and Hormesis In Disease And Agingmentioning

confidence: 99%

Lysosomes, Autophagy, and Hormesis in Cell Physiology, Pathology, and Age-Related Disease

Moore

2020

Dose-Response

View full text Add to dashboard Cite

Autophagy has been strongly linked with hormesis, however, it is only relatively recently that the mechanistic basis underlying this association has begun to emerge. Lysosomal autophagy is a group of processes that degrade proteins, protein aggregates, membranes, organelles, segregated regions of cytoplasm, and even parts of the nucleus in eukaryotic cells. These degradative processes are evolutionarily very ancient and provide a survival capability for cells that are stressed or injured. Autophagy and autophagic dysfunction have been linked with many aspects of cell physiology and pathology in disease processes; and there is now intense interest in identifying various therapeutic strategies involving its regulation. The main regulatory pathway for augmented autophagy is the mechanistic target of rapamycin (mTOR) cell signaling, although other pathways can be involved, such as 5′-adenosine monophosphate-activated protein kinase. Mechanistic target of rapamycin is a key player in the many highly interconnected intracellular signaling pathways and is responsible for the control of cell growth among other processes. Inhibition of mTOR (specifically dephosphorylation of mTOR complex 1) triggers augmented autophagy and the search is on the find inhibitors that can induce hormetic responses that may be suitable for treating many diseases, including many cancers, type 2 diabetes, and age-related neurodegenerative conditions.

show abstract

Section: Role Of Autophagy and Hormesis In Disease And Agingmentioning

confidence: 99%

Lysosomes, Autophagy, and Hormesis in Cell Physiology, Pathology, and Age-Related Disease

Moore

2020

Dose-Response

View full text Add to dashboard Cite

show abstract

“…The first of them is the modulation of the microRNA function by means of overexpression based on a viral vector or synthetic double-stranded microRNAs, and the second is the inhibition of microRNAs by chemically modified antisense oligonucleotides [ 920 ]. In addition, metformin, as well as the antibiotic enoxacin, can stimulate microRNA biogenesis, which mediates their gene and geroprotective activity [ 921 , 922 , 923 ].…”

Section: Pharmacological Interventions Protecting Genomementioning

confidence: 99%

Genome-Protecting Compounds as Potential Geroprotectors

Proshkina

Shaposhnikov

Moskalev

2020

IJMS

View full text Add to dashboard Cite

Throughout life, organisms are exposed to various exogenous and endogenous factors that cause DNA damages and somatic mutations provoking genomic instability. At a young age, compensatory mechanisms of genome protection are activated to prevent phenotypic and functional changes. However, the increasing stress and age-related deterioration in the functioning of these mechanisms result in damage accumulation, overcoming the functional threshold. This leads to aging and the development of age-related diseases. There are several ways to counteract these changes: (1) prevention of DNA damage through stimulation of antioxidant and detoxification systems, as well as transition metal chelation; (2) regulation of DNA methylation, chromatin structure, non-coding RNA activity and prevention of nuclear architecture alterations; (3) improving DNA damage response and repair; (4) selective removal of damaged non-functional and senescent cells. In the article, we have reviewed data about the effects of various trace elements, vitamins, polyphenols, terpenes, and other phytochemicals, as well as a number of synthetic pharmacological substances in these ways. Most of the compounds demonstrate the geroprotective potential and increase the lifespan in model organisms. However, their genome-protecting effects are non-selective and often are conditioned by hormesis. Consequently, the development of selective drugs targeting genome protection is an advanced direction.

show abstract

“…In recent years, studies have confirmed that miRNAs, through regulating gene expression at post-transcriptional level, participates in embryonic development and cell proliferation, differentiation and apoptosis and are closely related to the occurrence and development of tumor, heart diseases and other diseases. miR-34-5p, a member of the miR-34 family, has been reported to negatively regulate life span [25]. But the role of miR-34-5P in heart diseases has not been scarcely described.…”

Section: Introductionmentioning

confidence: 99%

LncRNA SNHG7 promotes cardiac remodeling by upregulating ROCK1 via sponging miR-34-5p

Wang

Zhang

et al. 2020

Aging

View full text Add to dashboard Cite

Previous studies have shown that lncRNA small nuclear RNA host gene 7 (lncRNA SNHG7) played an important role in cancer progression. However, the role of lncRNA SNHG7 in cardiac fibrosis is still poorly understood. In this study, the results of quantitative real time polymerase chain reaction (qRT-PCR) analysis showed that lncRNA SNHG7 was over expressed in the infarcted and peri-infarcted area in the left ventricle after MI in mice. Western blot analysis showed that knockdown of SNHG7 decreased the expression of collagen type 1 (Col1)and α-smooth muscle actin (α-SMA). Echocardiographic study suggested that inhibition of SNHG7 improved cardiac function after MI in mice. Luciferase assay indicated SNHG7 could act as a competing endogenous RNA (ceRNA) by sponging miR-34-5p. The MTT cell proliferation assay and 5-ethynyl-2'-deoxyuridine (EdU) labelling assay revealed that co-transfection of SNHG7 and miR-34-5p inhibited cell viability and proliferation of cardiac fibroblasts (CF). All the results indicated that lncRNA SNHG7 could promote cardiac fibrosis via targeting miR-34-5p through acting as a ceRNA in mice after MI. Silencing of SNHG7 could attenuate deposition of collagens and improve cardiac function. miR-34-5p could suppress the fibrogenesis of CF by targeting ROCK1 and abolish SNHG7-induced CF proliferation and fibroblast-to-myofibroblast transition.

show abstract

Enoxacin extends lifespan of C. elegans by inhibiting miR-34-5p and promoting mitohormesis

Cited by 43 publications

References 55 publications

Lysosomes, Autophagy, and Hormesis in Cell Physiology, Pathology, and Age-Related Disease

Lysosomes, Autophagy, and Hormesis in Cell Physiology, Pathology, and Age-Related Disease

Genome-Protecting Compounds as Potential Geroprotectors

LncRNA SNHG7 promotes cardiac remodeling by upregulating ROCK1 via sponging miR-34-5p

Contact Info

Product

Resources

About