Assessment of liver antioxidant status and mitochondrial membrane composition of Plasmodium berghei-infected mice treated with selected antimalarials

Doxorubicin (DXR) is a drug widely used in chemotherapy. Its mode of action is based on its intercalation properties, involving the inhibition of topoisomerase II. However, few studies have reported the mitochondrial effects of DXR while investigating cardiac toxicity induced by the treatment, mostly in pediatric cases. Here, we demonstrate that DXR alters the mitochondrial membrane composition associated with bioenergetic impairment and cell death in human cancer cells. The remodeling of the mitochondrial membrane was explained by phosphatidylserine decarboxylase (PSD) inhibition by DXR. PSD catalyzes phosphatidylethanolamine (PE) synthesis from phosphatidylserine (PS), and DXR altered the PS/PE ratio in the mitochondrial membrane. Moreover, we observed that DXR localized to the mitochondrial compartment and drug uptake was rapid. Evaluation of other topoisomerase II inhibitors did not show any impact on the mitochondrial membrane composition, indicating that the DXR effect was specific. Therefore, our findings revealed a side molecular target for DXR and PSD, potentially involved in DXR anti-cancer properties and the associated toxicity.

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Inhibitory Effect of Ursolic Acid on Ultraviolet B Radiation-Induced Oxidative Stress and Proinflammatory Response-Mediated Senescence in Human Skin Dermal Fibroblasts

Oxidative Medicine and Cellular Longevity ◽

10.1155/2020/1246510 ◽

2020 ◽

Vol 2020 ◽

pp. 1-17

Author(s):

Ramachandran Samivel ◽

Rajendra Prasad Nagarajan ◽

Umadevi Subramanian ◽

Adnan Ali Khan ◽

Ali Masmali ◽

...

Keyword(s):

Lipid Peroxidation ◽

Human Skin ◽

Mitochondrial Membrane ◽

Antioxidant Status ◽

Dermal Fibroblasts ◽

Ultraviolet B ◽

Uvb Radiation ◽

Proinflammatory Response ◽

Radiation Induced ◽

Apoptotic Induction

Ultraviolet radiation is an environmental carcinogenic agent that enhances inflammation and immunological reactions in the exposed human skin cells leading to oxidative photoaging of the epidermal and dermal segment. In the present study, we investigated the protective role of ursolic acid (UA) against ultraviolet B (UVB) radiation- induced photoaging an in vitro model of human skin dermal fibroblasts. UA-pretreated human skin dermal fibroblast (HDF) cells were exposed to UVB radiation to evaluated cell viability, reactive oxygen species (ROS), mitochondrial membrane potential, lipid peroxidation, antioxidant status, DNA damage, proinflammatory response, apoptotic induction, and matrix metalloproteinase (MMP) alteration. The UA pretreatment of HDFs mitigated the UVB irradiation-induced cytotoxicity, ROS generation, and mitochondrial membrane potential alteration and lipid peroxidation, depletion of antioxidant status, DNA damage, and apoptotic induction. UA pretreatment of HDFs also attenuated the UVB-induced expression of inflammatory (TNF-α and NF-κB) and apoptotic (p53, Bax, and caspase-3) and MMPs (MMP-2 and MMP-9) and enhanced the Bcl-2 protein levels in 20 μM UA treatment, when compared to concentrations. Hence, these results revealed that UA has the potential to mitigate UVB-induced extracellular damage by interfering with the ROS-mediated apoptotic induction and photoaging senescence and thus is a potential therapeutic agent to protect the skin against UVB-irradiation induced photooxidative damage.

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Influencing mitochondrial membrane composition and bioenergetics through omega-3 supplementation

The Journal of Physiology ◽

10.1113/jphysiol.2014.272419 ◽

2014 ◽

Vol 592 (9) ◽

pp. 1913-1914 ◽

Cited By ~ 1

Author(s):

Stewart Jeromson ◽

David J. Hunter

Keyword(s):

Mitochondrial Membrane ◽

Omega 3 ◽

Membrane Composition

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Mitochondrial Cristae Architecture and Functions: Lessons from Minimal Model Systems

Membranes ◽

10.3390/membranes11070465 ◽

2021 ◽

Vol 11 (7) ◽

pp. 465

Author(s):

Frédéric Joubert ◽

Nicolas Puff

Keyword(s):

Minimal Model ◽

Mitochondrial Membrane ◽

Energy Production ◽

Lipid Membrane ◽

Model Systems ◽

Eukaryotic Cells ◽

Membrane Composition ◽

Inner Mitochondrial Membrane ◽

Dynamic Membrane

Mitochondria are known as the powerhouse of eukaryotic cells. Energy production occurs in specific dynamic membrane invaginations in the inner mitochondrial membrane called cristae. Although the integrity of these structures is recognized as a key point for proper mitochondrial function, less is known about the mechanisms at the origin of their plasticity and organization, and how they can influence mitochondria function. Here, we review the studies which question the role of lipid membrane composition based mainly on minimal model systems.

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