Activity of matrix metallo proteinases (MMPs) and the tissue inhibitor of MMP (TIMP)‐1 in electromagnetic field‐exposed THP‐1 cells

Patruno, Antonia; Pesce, Mirko; Marrone, Alessandro; Speranza, Lorenza; Grilli, Alfredo; Lutiis, Maria Anna De; Felaco, Mario; Reale, Marcella

doi:10.1002/jcp.23024

Cited by 40 publications

(43 citation statements)

References 48 publications

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“…It is well known that the activities of MMPs are regulated by TIMPs through their NH 2 -terminal inhibitory domain (34,39,48,50,52). Hence the levels of TIMPs were determined in lungs of SIRT1 ϩ/Ϫ and SIRT1 Tg mice as well as WT littermates in response to CS exposure.…”

Section: Overexpression Of Sirt1 Decreases the Protein Level And Actimentioning

confidence: 99%

“…Genetic overexpression of MMP-9 causes air space enlargement, whereas deficiency of MMP-12 attenuates cigarette smoke (CS)-induced pulmonary emphysema in mice (14,16). It has been shown that TIMPs are subjected to posttranslational modifications, such as acetylation, oxidation, and nitration, thereby regulating their ability to inhibit MMPs (34,39,48,50,52). However, it is unknown whether TIMPs undergo these posttranslational modifications, particularly in response to CS leading to upregulation of MMPs, and whether SIRT1 has a regulatory role in redressing the TIMP/MMP imbalance.…”

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confidence: 99%

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SIRT1 redresses the imbalance of tissue inhibitor of matrix metalloproteinase-1 and matrix metalloproteinase-9 in the development of mouse emphysema and human COPD

Yao

Hwang

Sundar

et al. 2013

American Journal of Physiology-Lung Cellular and Molecular Phys

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I. SIRT1 redresses the imbalance of tissue inhibitor of matrix metalloproteinase-1 and matrix metalloproteinase-9 in the development of mouse emphysema and human COPD. Am J Physiol Lung Cell Mol Physiol 305: L615-L624, 2013. First published September 13, 2013 doi:10.1152/ajplung.00249.2012, a protein/ histone deacetylase, protects against the development of pulmonary emphysema. However, the molecular mechanisms underlying this observation remain elusive. The imbalance of tissue inhibitor of matrix metalloproteinases (TIMPs)/matrix metalloproteinases (MMPs) plays an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD)/emphysema. We hypothesized that SIRT1 protects against emphysema by redressing the imbalance between MMPs and TIMPs. To test this hypothesis, SIRT1-deficient and overexpressing/transgenic mice were exposed to cigarette smoke (CS). The protein level and activity of MMP-9 were increased in lungs of SIRT1-deficient mice exposed to CS compared with wild-type (WT) littermates, and these effects were attenuated by SIRT1 overexpression. SIRT1 deficiency decreased the level of TIMP-1, which was augmented in SIRT1 transgenic mice compared with WT littermates by CS. However, the level of MMP-2, MMP-12, TIMP-2, TIMP-3, or TIMP-4 was not altered by SIRT1 in response to CS exposure. SIRT1 reduction was associated with imbalance of TIMP-1 and MMP-9 in lungs of smokers and COPD patients. Mass spectrometry and immunoprecipitation analyses revealed that TIMP-1 acetylation on specific lysine residues was increased, whereas its interaction with SIRT1 and MMP-9 was reduced in mouse lungs with emphysema, as well as in lungs of smokers and COPD patients. SIRT1 deficiency increased CS-induced TIMP-1 acetylation, and these effects were attenuated by SIRT1 overexpression. These results suggest that SIRT1 protects against COPD/emphysema, in part, via redressing the TIMP-1/MMP-9 imbalance involving TIMP-1 deacetylation. Thus redressing the TIMP-1/MMP-9 imbalance by pharmacological activation of SIRT1 is an attractive approach in the intervention of COPD. SIRT1; cigarette smoke; MMPs; TIMPs; emphysema; COPD SIRTUIN1 (SIRT1), a type III histone/protein deacetylase, plays an important role in inflammation, stress resistance, and cellular senescence/aging through the deacetylation of histones, transcription factors, and signaling molecules. It is a redoxsensitive deacetylase that can be posttranslationally modified by oxidants and carbonyl stress, leading to proteasomal degradation (9,36,59). This may be one of the reasons for the reduction of SIRT1 level in peripheral lung tissues of smokers and patients with chronic obstructive pulmonary disease (COPD)/emphysema (36, 55). Recently, we have shown that SIRT1 protects against pulmonary emphysema in mice (55). However, the mechanisms of SIRT1 in preventing the progression of COPD/emphysema are not fully understood.The imbalance of tissue inhibitors of metalloproteinases (TIMPs)/matrix metalloproteinases (MMPs) in the lungs has been implicated in the d...

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Section: Overexpression Of Sirt1 Decreases the Protein Level And Actimentioning

confidence: 99%

mentioning

confidence: 99%

SIRT1 redresses the imbalance of tissue inhibitor of matrix metalloproteinase-1 and matrix metalloproteinase-9 in the development of mouse emphysema and human COPD

Yao

Hwang

Sundar

et al. 2013

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…In the EL-EMF exposure group, MMP-2 expression increased. Other studies showed that an increasing MMP-2 gene expression took place when SK-OV-3 ovarian cancer cells were exposed to EL-EMF (Patruno et al 2012). But these two factors act together to reduce the expression of these genes.…”

Section: Semi-quantitative Rt-pcr Resultsmentioning

confidence: 95%

Extremely low frequency electromagnetic field sensitizes cisplatin-resistant human ovarian adenocarcinoma cells via P53 activation

2015

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In the following study, extremely low frequency electromagnetic fields (EL-EMF) radiation was used to restore sensitivity in the cisplatin-resistant A2780 ovarian cancer cells. For this purpose A2780 cells were treated with different doses of cisplatin and EL-EMF (50 Hz, 200 gauss, and 2 h) alone. Cytotoxicity was the measurement using MTT assay. After calculating IC 50 for cisplatin (90 lg/ml) a lower concentration from IC 50 (30 and 60 lg/ml) was used to be combined with EL-EMF. We compare the effects of each cisplatin, EL-EMF and combination groups using acridine orange-propidium iodide (AO/PI) and DAPI staining, caspase 3/9 activation assay and Annexin/PI assay. We also assessed changes in P53 and Matrix metalloproteinases 2 (MMPs) gene expression with semi-quantitative RT-PCR. Results indicated an EL-EMF-dependent proliferative decrease which was found \10 %, and occurred independently of cisplatin. The decreased proliferation rate for 30 and 60 lg/ml cisplatin was about 20 and 40 %, respectively, while for synergistic groups 30 and 60 lg/ml cisplatin with 2 h EL-EMF exposer, showed 47 and 71 % decrease in viability in rats. DAPI staining indicated that chromatin break down significantly increased in synergistic groups. Acridine orange staining also confirmed MTT assay results. Caspase activity significantly increased in the combined groups. Semi-quantitative RT-PCR showed that in synergistic groups of cisplatin and EL-EMF, expression of P53 was increased but the expression level of MPP-2 gene decreased. Results from this study showed that changes generated by the non-invasive EL-EMF can make resistant cells sensitive to cisplatin.

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“…MMPs are enzymes that are essential for this process. MMPs play a role in the degradation of the extracellular matrix by promoting epithelial-mesenchymal transition, promoting the activation of growth factors, their receptors and angiogenesis, and facilitating tumor invasion and metastasis (24)(25)(26)(27). Previous studies revealed that the expression of MMP-2 in breast cancer tissue is higher compared with normal breast tissue.…”

Section: Discussionmentioning

confidence: 99%

Expression of WTH3 in breast cancer tissue and the effects on the biological behavior of breast cancer cells

Gan

Zuo

Wang

et al. 2015

Experimental and Therapeutic Medicine

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Abstract. The aim of the present study was to investigate the expression of WTH3 in tumor and normal breast tissue. The mRNA and protein expression levels of WTH3 were detected using reverse transcription quantitative polymerase chain reaction and western blot analysis, respectively. In addition, matrix metalloproteinase (MMP)-2 protein expression was measured. The effect of WTH3 expression on the proliferation activity of breast cancer cells was detected using a Cell Counting Kit-8 assay. Furthermore, the effects of WTH3 on the invasion and migration ability of the breast cancer cells was investigated. The results revealed that WTH3 was able to significantly inhibit the proliferation of the MCF-7 and MDA-MB-231 breast cancer cell lines. In addition, the invasion and migration assay demonstrated that WTH3 was able to inhibit the invasion and migration of breast cancer cells. Western blot analysis revealed that increased expression of WTH3 resulted in decreased expression levels of MMP-2, which has an important function in the metastasis of cancer cells. In conclusion, WTH3 expression differed between the tumor and normal breast tissues. WTH3 was able to inhibit the proliferation of breast cancer cells and decrease their invasion ability. Thus, WTH3 may be a promising target for breast cancer therapy in the future.

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Activity of matrix metallo proteinases (MMPs) and the tissue inhibitor of MMP (TIMP)‐1 in electromagnetic field‐exposed THP‐1 cells

Cited by 40 publications

References 48 publications

SIRT1 redresses the imbalance of tissue inhibitor of matrix metalloproteinase-1 and matrix metalloproteinase-9 in the development of mouse emphysema and human COPD

SIRT1 redresses the imbalance of tissue inhibitor of matrix metalloproteinase-1 and matrix metalloproteinase-9 in the development of mouse emphysema and human COPD

Extremely low frequency electromagnetic field sensitizes cisplatin-resistant human ovarian adenocarcinoma cells via P53 activation

Expression of WTH3 in breast cancer tissue and the effects on the biological behavior of breast cancer cells

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