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Start Over Author "Bonafe, M" Journal cell death & differentiation
2 results on '"Bonafe, M"'

1. Apoptosis-resistant phenotype in HL-60-derived cells HCW-2 is related to changes in expression of stress-induced proteins that impact on redox status and mitochondrial metabolism.

Author

Salvioli, S, Storci, G, Pinti, M, Quaglino, D, Moretti, L, Merlo-Pich, M, Lenaz, G, Filosa, S, Fico, A, Bonafe, M, Monti, D, Troiano, L, Nasi, M, Cossarizza, A, and Franceschi, C

Subjects
TUMORS, DRUG resistance, APOPTOSIS, CANCER treatment, DRUG therapy
Abstract

The onset of resistance to drug-induced apoptosis of tumour cells is a major problem in cancer therapy. We studied a drug-selected clone of promyelocytic HL-60 cells, called HCW-2, which display a complex resistance to a wide variety of apoptosis-inducing agents and we found that these cells show a dramatic increase in the expression of heat shock proteins (Hsps) 70 and 27, while the parental cell line does not. It is known that stress proteins such as Hsps can confer resistance to a variety of damaging agents other than heat shock, such as TNF- α, monocyte-induced cytoxicity, and also play a role in resistance to chemotherapy. This elevated expression of Hsps is paralleled by an increased activity of mitochondrial metabolism and pentose phosphate pathway, this latter leading to high levels of glucose-6-phosphate dehydrogenase and, consequently, of glutathione. Thus, the apoptotic-deficient phenotype is likely because of the presence of high levels of stress response proteins and GSH, which may confer resistance to apoptotic agents, including chemotherapic drugs. Moreover, the fact that in HCW-2 cells Hsp70 are mainly localised in mitochondria may account for the increased performances of mitochondrial metabolism. These observations could have some implications for the therapy of cancer, and for the design of combined strategies that act on antioxidant defences of the neoplastic cell. [ABSTRACT FROM AUTHOR]

Published
2003
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2. Genomic stability, anti-inflammatory phenotype, and up-regulation of the RNAseH2 in cells from centenarians

Author

Silvia Latini, Francesco Fabbri, Manuela Ferracin, Anna Tesei, Sabrina De Carolis, Stefano Salvioli, Elena Marasco, Noémie Gensous, Fabiola Olivieri, Maria Giulia Bacalini, Chiara Arienti, Massimiliano Bonafè, Michele Zanoni, Gianluca Storci, Emanuela Mensà, Anna Sarnelli, Alessio Papi, Spartaco Santi, Claudio Franceschi, Paolo Garagnani, Storci G., De Carolis S., Papi A., Bacalini M.G., Gensous N., Marasco E., Tesei A., Fabbri F., Arienti C., Zanoni M., Sarnelli A., Santi S., Olivieri F., Mensa E., Latini S., Ferracin M., Salvioli S., Garagnani P., Franceschi C., and Bonafe M.

Subjects
Adult, Male, 0301 basic medicine, DNA repair, DNA damage, Longevity, Ribonuclease H, Breast Neoplasms, Inflammation, Biology, Methylation, Article, Extracellular Vesicles, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Interferon, medicine, Humans, Molecular Biology, Cellular Senescence, Aged, Aged, 80 and over, Interleukin-6, Telomere Homeostasis, Interferon-beta, Cell Biology, Fibroblasts, Middle Aged, Phenotype, Plaque, Atherosclerotic, DNA damage response, centenarians, RNA:DNA hybrids, inflammation, 3. Good health, Telomere, Cell biology, Comet assay, MicroRNAs, 030104 developmental biology, Genetic Loci, 030220 oncology & carcinogenesis, Cancer cell, Female, medicine.symptom, DNA Damage, medicine.drug
Abstract

Current literature agrees on the notion that efficient DNA repair favors longevity across evolution. The DNA damage response machinery activates inflammation and type I interferon signaling. Both pathways play an acknowledged role in the pathogenesis of a variety of age-related diseases and are expected to be detrimental for human longevity. Here, we report on the anti-inflammatory molecular make-up of centenarian’s fibroblasts (low levels of IL-6, type 1 interferon beta, and pro-inflammatory microRNAs), which is coupled with low level of DNA damage (measured by comet assay and histone-2AX activation) and preserved telomere length. In the same cells, high levels of the RNAseH2C enzyme subunit and low amounts of RNAseH2 substrates, i.e. cytoplasmic RNA:DNA hybrids are present. Moreover, RNAseH2C locus is hypo-methylated and RNAseH2C knock-down up-regulates IL-6 and type 1 interferon beta in centenarian’s fibroblasts. Interestingly, RNAseH2C locus is hyper-methylated in vitro senescent cells and in tissues from atherosclerotic plaques and breast tumors. Finally, extracellular vesicles from centenarian’s cells up-regulate RNAseH2C expression and dampen the pro-inflammatory phenotype of fibroblasts, myeloid, and cancer cells. These data suggest that centenarians are endowed with restrained DNA damage-induced inflammatory response, that may facilitate their escape from the deleterious effects of age-related chronic inflammation.

Published
2019

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