Lucas A. Maddalena
Brock University
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Featured researches published by Lucas A. Maddalena.
Longevity & Healthspan | 2014
Jeffrey A. Stuart; Lucas A. Maddalena; Max Merilovich; Ellen L. Robb
Since its inception more than four decades ago, the Mitochondrial Free Radical Theory of Aging (MFRTA) has served as a touchstone for research into the biology of aging. The MFRTA suggests that oxidative damage to cellular macromolecules caused by reactive oxygen species (ROS) originating from mitochondria accumulates in cells over an animal’s lifespan and eventually leads to the dysfunction and failure that characterizes aging. A central prediction of the theory is that the ability to ameliorate or slow this process should be associated with a slowed rate of aging and thus increased lifespan. A vast pool of data bearing on this idea has now been published. ROS production, ROS neutralization and macromolecule repair have all been extensively studied in the context of longevity. We review experimental evidence from comparisons between naturally long- or short-lived animal species, from calorie restricted animals, and from genetically modified animals and weigh the strength of results supporting the MFRTA. Viewed as a whole, the data accumulated from these studies have too often failed to support the theory. Excellent, well controlled studies from the past decade in particular have isolated ROS as an experimental variable and have shown no relationship between its production or neutralization and aging or longevity. Instead, a role for mitochondrial ROS as intracellular messengers involved in the regulation of some basic cellular processes, such as proliferation, differentiation and death, has emerged. If mitochondrial ROS are involved in the aging process, it seems very likely it will be via highly specific and regulated cellular processes and not through indiscriminate oxidative damage to macromolecules.
Carbohydrate Research | 2016
Ravi Shekar Yalagala; Sina Atrin Mazinani; Lucas A. Maddalena; Jeffrey A. Stuart; Fengyang Yan; Hongbin Yan
BODIPY fluorophores bearing azide or terminal alkyne functions were conjugated with glycans modified with terminal alkyne or azido through the Cu(I)-catalyzed 1,3-dipolar azide-alkyne cycloaddition (CuAAC) chemistry under microwave heating while these reactions did not proceed when heated in an oil-bath. The BODIPY-glycan conjugate product 8a undergoes self-assembly into liposomes when hydrated. Formation of liposomes was confirmed by both bright field and confocal microscopy. Fluorescent emission within the liposome was shifted from green to red due to effective high concentrations.
Biochimica et Biophysica Acta | 2017
Lucas A. Maddalena; Mikel Ghelfi; Jeffrey Atkinson; Jeffrey A. Stuart
A variety of mitochondria-targeted small molecules have been invented to manipulate mitochondrial redox activities and improve function in certain disease states. 3-Hydroxypropyl-triphenylphosphonium-conjugated imidazole-substituted oleic acid (TPP-IOA) was developed as a specific inhibitor of cytochrome c peroxidase activity that inhibits apoptosis by preventing cardiolipin oxidation and cytochrome c release to the cytosol. Here we evaluate the effects of TPP-IOA on oxidative phosphorylation in isolated mitochondria and on mitochondrial function in live cells. We demonstrate that, at concentrations similar to those required to achieve inhibition of cytochrome c peroxidase activity, TPP-IOA perturbs oxidative phosphorylation in isolated mitochondria. In live SH-SY5Y cells, TPP-IOA partially collapsed mitochondrial membrane potential, caused extensive fragmentation of the mitochondrial network, and decreased apparent mitochondrial abundance within 3h of exposure. Many cultured cell lines rely primarily on aerobic glycolysis, potentially making them less sensitive to small molecules disrupting oxidative phosphorylation. We therefore determined the anti-apoptotic efficacy of TPP-IOA in SH-SY5Y cells growing in glucose or in galactose, the latter of which increases reliance on oxidative phosphorylation for ATP supply. The anti-apoptotic activity of TPP-IOA that was observed in glucose media was not seen in galactose media. It therefore appears that, at concentrations required to inhibit cytochrome c peroxidase activity, TPP-IOA perturbs oxidative phosphorylation. In light of these data it is predicted that potential future therapeutic applications of TPP-IOA will be restricted to highly glycolytic cell types with limited reliance on oxidative phosphorylation.
Acta Histochemica | 2017
Andrew Valente; Lucas A. Maddalena; Ellen L. Robb; Fereshteh Moradi; Jeffrey A. Stuart
Biochemical and Biophysical Research Communications | 2017
Ellen L. Robb; Fereshteh Moradi; Lucas A. Maddalena; Andrew Valente; Joao Fonseca; Jeffrey A. Stuart
Comparative Biochemistry and Physiology A-molecular & Integrative Physiology | 2012
Ellen L. Robb; Lucas A. Maddalena; Valerie A. Dunlop; Tamara Foster; Jeffrey A. Stuart
Biochemical and Biophysical Research Communications | 2017
Lucas A. Maddalena; Shehab M. Selim; Joao Fonseca; Holt Messner; Shannon McGowan; Jeffrey A. Stuart
Free Radical Biology and Medicine | 2017
Marco Fiocchetti; Lucas A. Maddalena; Fereshteh Moradi; Joao Couto Fonseca; Mohamed Rezk; Ryan Hallam; Gregory M.J. Foran; Aleksandar Necakov; Maria Marino; Jeffrey A. Stuart
Free Radical Biology and Medicine | 2017
Fereshteh Moradi; Lucas A. Maddalena; Jeffrey Allan Stuart; Joao Couto Fonseca
Free Radical Biology and Medicine | 2015
Lucas A. Maddalena; Jeffrey Atkinson; Jeffrey A. Stuart