Protein carbonylation, cellular dysfunction, and disease progression

Dalle‐Donne, Isabella; Aldini, Giancarlo; Colombo, Roberto; Rossi, Ranieri; Milzani, Aldo

doi:10.1111/j.1582-4934.2006.tb00407.x

Cited by 728 publications

(590 citation statements)

References 143 publications

(193 reference statements)

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“…Thus, through the integration of multiple omic techniques performed in the current study along with previous research, we hypothesize that among the many anti-leukemic activities of PTL, its ability to induce oxidative stress is the most important. Notably, oxidative stress is known to induce protein-misfolding stress as correct folding of proteins is usually redox-sensitive (39,40). Therefore, we also hypothesize that the increase of protein misfolding stress upon PTL treatment is a secondary consequence of PTL-induced oxidative stress.…”

Section: Identification Of the Proteomic Interactome Of Ptl In Primarymentioning

confidence: 99%

Rational Design of a Parthenolide-based Drug Regimen That Selectively Eradicates Acute Myelogenous Leukemia Stem Cells

Pei¹,

Minhajuddin²,

D’Alessandro

et al. 2016

Journal of Biological Chemistry

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Although multidrug approaches to cancer therapy are common, few strategies are based on rigorous scientific principles. Rather, drug combinations are largely dictated by empirical or clinical parameters. In the present study we developed a strategy for rational design of a regimen that selectively targets human acute myelogenous leukemia (AML) stem cells. As a starting point, we used parthenolide, an agent shown to target critical mechanisms of redox balance in primary AML cells. Next, using proteomic, genomic, and metabolomic methods, we determined that treatment with parthenolide leads to induction of compensatory mechanisms that include up-regulated NADPH production via the pentose phosphate pathway as well as activation of the Nrf2-mediated oxidative stress response pathway. Using this knowledge we identified 2-deoxyglucose and temsirolimus as agents that can be added to a parthenolide regimen as a means to inhibit such compensatory events and thereby further enhance eradication of AML cells. We demonstrate that the parthenolide, 2-deoxyglucose, temsirolimus (termed PDT) regimen is a potent means of targeting AML stem cells but has little to no effect on normal stem cells. Taken together our findings illustrate a comprehensive approach to designing combination anticancer drug regimens.Numerous studies have documented the biological complexity of human tumor cell populations in which genetic, epigenetic, biochemical, and metabolic properties can often be quite heterogeneous (1, 2). As a result, complicated multidrug regimens are often employed to target various components of tumor biology and/or acquired drug resistance (3, 4). However, the rationale behind the design of multidrug regimens is usually inconsistent and often driven by pragmatism more than scientific rigor. Thus, establishing more effective means by which to identify optimal drug regimens is an important priority, particularly with the recent emergence of a broad range of targeted agents.

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Section: Identification Of the Proteomic Interactome Of Ptl In Primarymentioning

confidence: 99%

Rational Design of a Parthenolide-based Drug Regimen That Selectively Eradicates Acute Myelogenous Leukemia Stem Cells

Pei¹,

Minhajuddin²,

D’Alessandro

et al. 2016

Journal of Biological Chemistry

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“…Thiols, in fact, have the characteristic to be oxidized in an almost irreversible manner and this identifies them as key components in the mechanism involved in redox balance. In humans, research on ROS and oxidative stress is hampered by methodological difficulties in assessing the levels of markers of oxidative stress in biological samples [29,30]. In particular, the direct evaluation of the level of oxidative stress in cell-free biological fluids is very difficult since they lack ROS producing cells.…”

Section: Discussionmentioning

confidence: 99%

Protein modification as oxidative stress marker in follicular fluid from women with polycystic ovary syndrome: the effect of inositol and metformin

Piomboni

Focarelli

Capaldo

et al. 2014

J Assist Reprod Genet

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Purpose The purpose of this study was to evaluate the oxidative stress status (OS) of follicular fluid (FF) and the oocyte quality in women with polycystic ovary syndrome (PCOS) undergoing different ovarian stimulation protocols. Methods FF samples were collected after gonadotropin administration in association or not with metformin or D-chiro-inositol (DCI). OS status was then evaluated by checking the follicular fluid protein oxidation profile after specific labeling of aminoacidic free-SH groups, and two-dimensional electrophoresis followed by qualitative and semiquantitative analysis. Oocyte quality was assessed by international morphological criteria. Results Our data indicated that both treatments, even if to different extent, recovered a significantly high level of free-SH groups in FF proteins of PCOS women clearly indicating a decrease of OS level with respect to that found in FF samples from gonadotropins alone treated women. A higher number of good quality MII oocytes was also observed in DCI (P<0.05) or metformin (P<0.05) study groups in comparison to untreated control group. Conclusion A natural supplement and a drug both showed a statistically significant positive effect on follicular milieu by decreasing the oxidative damage on FF proteins, as well as in recovering good quality oocytes.

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“…The precipitated proteins were resuspended in 0.2% 2,4-dinitrophenyl hydrazine and incubated for 1 h at 37°C. Subsequently, proteins were precipitated again with trichloroacetic acid, centrifuged at 4,000 g, washed with ethanol/ethyl acetate (1:1), dissolved in 6 mmol/l guanidine hydrochloride, and the absorbance measured spectrophotometrically at 370 nm [11,19].…”

Section: Methodsmentioning

confidence: 99%

Exercise restores endothelial function independently of weight loss or hyperglycaemic status in db/db mice

et al. 2008

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Aims/hypothesis Exercise ameliorates oxidative stressmediated diabetic vascular endothelial dysfunction through poorly defined mechanisms. We hypothesised that, in addition to improving metabolic parameters, upregulation of antioxidants such as superoxide dismutase (SOD) mediates exercise-induced reductions of oxidative stress and increased nitric oxide (NO) bioavailability, and also restores vasodilatation. Methods Type 2 diabetic db/db and normoglycaemic wildtype mice were exercised at moderate intensity for 1 h a day for 7 weeks, leading to a 10% body weight loss. Sedentary animals or those undergoing a low-intensity exercise regimen causing non-significant weight loss were also used. We examined aortic endothelial cell function, NO bioavailability and various biomarkers of oxidative stress. Results Moderate-intensity exercise lowered body weight, increased mitochondrial manganese SOD (MnSOD) and both total and phosphorylated (Ser1177) endothelial nitric oxide synthase (eNOS) protein production; it also reduced wholebody (plasma 8-isoprostane) and tissue oxidative stress (nitrotyrosine immunostaining or protein carbonyl levels in the aorta). Low-intensity exercise did not alter body weight; however, it upregulated cytosolic Cu/Zn-SOD instead of MnSOD, and still demonstrated all the above benefits in the db/db aorta. Importantly, both exercise protocols improved endothelial-dependent vasodilatation and NO bioavailability without altering hyperglycaemic status in db/db mice. Conclusions/interpretation Exercise reverses diabetic vascular endothelial dysfunction independently of improvements in body weight or hyperglycaemia. Our data suggest that upregulation of eNOS and specific SOD isoforms could play important roles in improving NO bioavailability, as well as in reversing endothelial dysfunction in type 2 diabetes patients through lifestyle modifications in the management of diabetes.

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Protein carbonylation, cellular dysfunction, and disease progression

Cited by 728 publications

References 143 publications

Rational Design of a Parthenolide-based Drug Regimen That Selectively Eradicates Acute Myelogenous Leukemia Stem Cells

Rational Design of a Parthenolide-based Drug Regimen That Selectively Eradicates Acute Myelogenous Leukemia Stem Cells

Protein modification as oxidative stress marker in follicular fluid from women with polycystic ovary syndrome: the effect of inositol and metformin

Exercise restores endothelial function independently of weight loss or hyperglycaemic status in db/db mice

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