4-Hydroxynonenal Contributes to Fibroblast Senescence in Skin Photoaging Evoked by UV-A Radiation

Solar ultraviolet A (UV-A) radiation promotes a huge variety of damages on connective tissues and dermal fibroblasts, including cellular senescence, a major contributor of skin photoaging. The mechanisms of skin photoaging evoked by UV-A partly involve the generation of reactive oxygen species and lipid peroxidation. We previously reported that 4-hydroxynonenal (HNE), a lipid peroxidation-derived aldehyde, forms adducts on elastin in the skins of UV-A irradiated hairless mice, possibly contributing to actinic elastosis. In the present study, we investigated whether and how HNE promotes fibroblast senescence in skin photoaging. Dermal fibroblasts of skins from UV-A-exposed hairless mice exhibited an increased number of γH2AX foci characteristic of cell senescence, together with an accumulation of HNE adducts partly colocalizing with the cytoskeletal protein vimentin. Murine fibroblasts exposed to UV-A radiation (two cycles of 15 J/cm2), or HNE (30 µM, 4 h), exhibited senescence patterns characterized by an increased γH2AX foci expression, an accumulation of acetylated proteins, and a decreased expression of the sirtuin SIRT1. HNE adducts were detected on vimentin in cultured fibroblasts irradiated by UV-A or incubated with HNE. The HNE scavenger carnosine prevented both vimentin modification and fibroblast senescence evoked by HNE in vitro and in the skins of UV-A-exposed mice. Altogether, these data emphasize the role of HNE and lipid peroxidation-derived aldehydes in fibroblast senescence, and confirm the protective effect of carnosine in skin photoaging.

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The Role of Lipid Peroxidation Products in the Regulation of Protein Kinase C Activity in Vitro

Advances in Experimental Medicine and Biology - Eicosanoids and Other Bioactive Lipids in Cancer, Inflammation, and Radiation Injury 2 ◽

10.1007/978-1-4615-5325-0_47 ◽

1997 ◽

pp. 339-348 ◽

Cited By ~ 2

Author(s):

Elena L. Mal’tseva

Keyword(s):

Lipid Peroxidation ◽

Protein Kinase C ◽

Protein Kinase ◽

Lipid Peroxidation Products ◽

Kinase C ◽

Protein Kinase C Activity

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LTBP1 promotes fibrillin incorporation into the extracellular matrix

10.1101/2021.12.16.473056 ◽

2021 ◽

Author(s):

Matthias Przyklenk ◽

Veronika Georgieva ◽

Fabian Metzen ◽

Sebastian Mostert ◽

Birgit Kobbe ◽

...

Keyword(s):

Extracellular Matrix ◽

Matrix Protein ◽

Wide Spectrum ◽

Extracellular Matrix Protein ◽

Connective Tissues ◽

Pathogenic Variants ◽

Human Pathology ◽

Fibrillin 1

LTBP1 is a large extracellular matrix protein and an associated ligand of fibrillin-microfibrils. Knowledge of LTBP1 functions is largely limited to its role in targeting and sequestering TGFβ growth factors within the extracellular matrix, thereby regulating their bioavailability. However, the recent description of a wide spectrum of phenotypes in multiple tissues in patients harboring LTBP1 pathogenic variants suggests a multifaceted role of the protein in the homeostasis of connective tissues. To better understand the human pathology caused by LTBP1 deficiency it is important to investigate its functional role in extracellular matrix formation. In this study, we show that LTBP1 coordinates the incorporation of fibrillin-1 and -2 into the extracellular matrix in vitro. We also demonstrate that this function is differentially exerted by the two isoforms, the short and long forms of LTBP1. Thereby our findings uncover a novel TGFβ-independent LTBP1 function potentially contributing to the development of connective tissue disorders.

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The Paracrine Role of Endothelial Cells in Bone Formation via CXCR4/SDF-1 Pathway

Cells ◽

10.3390/cells9061325 ◽

2020 ◽

Vol 9 (6) ◽

pp. 1325

Author(s):

Tal Tamari ◽

Rawan Kawar-Jaraisy ◽

Ofri Doppelt ◽

Ben Giladi ◽

Nadin Sabbah ◽

...

Keyword(s):

Endothelial Cells ◽

Bone Formation ◽

Mesenchymal Cells ◽

Dermal Fibroblasts ◽

Bioactive Molecules ◽

Ectopic Bone ◽

Ectopic Mineralization ◽

Shed Light

Vascularization is a prerequisite for bone formation. Endothelial progenitor cells (EPCs) stimulate bone formation by creating a vascular network. Moreover, EPCs secrete various bioactive molecules that may regulate bone formation. The aim of this research was to shed light on the pathways of EPCs in bone formation. In a subcutaneous nude mouse ectopic bone model, the transplantation of human EPCs onto β-TCP scaffold increased angiogenesis (p < 0.001) and mineralization (p < 0.01), compared to human neonatal dermal fibroblasts (HNDF group) and a-cellular scaffold transplantation (β-TCP group). Human EPCs were lining blood vessels lumen; however, the majority of the vessels originated from endogenous mouse endothelial cells at a higher level in the EPC group (p < 01). Ectopic mineralization was mostly found in the EPCs group, and can be attributed to the recruitment of endogenous mesenchymal cells ten days after transplantation (p < 0.0001). Stromal derived factor-1 gene was expressed at high levels in EPCs and controlled the migration of mesenchymal and endothelial cells towards EPC conditioned medium in vitro. Blocking SDF-1 receptors on both cells abolished cell migration. In conclusion, EPCs contribute to osteogenesis mainly by the secretion of SDF-1, that stimulates homing of endothelial and mesenchymal cells. This data may be used to accelerate bone formation in the future.

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Mécanisme moléculaire de l'effet protecteur de la vitamine E dans l'athérosclérose

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y02-076 ◽

2002 ◽

Vol 80 (7) ◽

pp. 662-669 ◽

Cited By ~ 4

Author(s):

Abdelouahed Khalil

Keyword(s):

Lipid Peroxidation ◽

Vitamin E ◽

Vascular Diseases ◽

Epidemiologic Studies ◽

Low Density Lipoproteins ◽

Alpha Tocopherol ◽

Low Density ◽

Prooxidant Effect

Oxidation of low-density lipoproteins constitutes the first step of a very complex process leading to atherosclerosis. Vitamin E, and principally alpha-tocopherol, is considered as the principal inhibitor of lipid peroxidation. Some studies showed the beneficial role of vitamin E in the prevention and reduction of atherosclerosis and its associated pathologies. However, other in vitro studies advance a prooxidant role of vitamin E. The results of the epidemiologic studies are difficult to generalize without taking account of the clinical randomized tests. In this work, we reviewed the principal studies devoted to the role of vitamin E and discussed the assumption of a prooxidant effect of this molecule.Key words: vitamin E, low-density lipoproteins (LDL), lipid peroxidation, cardio-vascular diseases.

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Roles of Lipid Peroxidation-Derived Electrophiles in Pathogenesis of Colonic Inflammation and Colon Cancer

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.665591 ◽

2021 ◽

Vol 9 ◽

Author(s):

Lei Lei ◽

Jianan Zhang ◽

Eric A. Decker ◽

Guodong Zhang

Keyword(s):

Colorectal Cancer ◽

Lipid Peroxidation ◽

Critical Role ◽

Redox Stress ◽

Colonic Inflammation ◽

Colon Tumorigenesis ◽

Inflammatory Bowel

Redox stress is a common feature of gut disorders such as colonic inflammation (inflammatory bowel disease or IBD) and colorectal cancer (CRC). This leads to increased colonic formation of lipid-derived electrophiles (LDEs) such as 4-hydroxynonenal (4-HNE), malondialdehyde (MDA), trans, trans-2,4-decadienal (tt-DDE), and epoxyketooctadecenoic acid (EKODE). Recent research by us and others support that treatment with LDEs increases the severity of colitis and exacerbates the development of colon tumorigenesis in vitro and in vivo, supporting a critical role of these compounds in the pathogenesis of IBD and CRC. In this review, we will discuss the effects and mechanisms of LDEs on development of IBD and CRC and lifestyle factors, which could potentially affect tissue levels of LDEs to regulate IBD and CRC development.

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In vitro lipid peroxidation of human serum catalyzed by cupric ion: Antioxidant rather than prooxidant role of ascorbate

Life Sciences ◽

10.1016/0024-3205(92)90206-5 ◽

1992 ◽

Vol 50 (12) ◽

pp. 875-882 ◽

Cited By ~ 37

Author(s):

Amitava Dasgupta ◽

Teresita Zdunek

Keyword(s):

Lipid Peroxidation ◽

Human Serum ◽

Cupric Ion

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Standardized Kaempferia parviflora Extract Inhibits Intrinsic Aging Process in Human Dermal Fibroblasts and Hairless Mice by Inhibiting Cellular Senescence and Mitochondrial Dysfunction

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2017/6861085 ◽

2017 ◽

Vol 2017 ◽

pp. 1-14 ◽

Cited By ~ 4

Author(s):

Ji-Eun Park ◽

Seon Wook Woo ◽

Mi-Bo Kim ◽

Changhee Kim ◽

Jae-Kwan Hwang

Keyword(s):

Cell Cycle ◽

Mitochondrial Dysfunction ◽

Cellular Senescence ◽

Aging Process ◽

Dermal Fibroblasts ◽

Elastic Fibers ◽

Kaempferia Parviflora ◽

Hairless Mice

Intrinsic skin aging is a complex biological phenomenon mainly caused by cellular senescence and mitochondrial dysfunction. This study evaluated the inhibitory effect of Kaempferia parviflora Wall ex. Baker ethanol extract (KPE) on H2O2-stimulated cellular senescence and mitochondrial dysfunction both in vitro and in vivo. KPE significantly increased cell growth and suppressed senescence-associated β-galactosidase activation. KPE inhibited the expression of cell-cycle inhibitors (p53, p21, p16, and pRb) and stimulated the expression of cell-cycle activators (E2F1 and E2F2). H2O2-induced hyperactivation of the phosphatidylinositol 3-kinase/protein kinase B (AKT) signaling pathway was suppressed by KPE through regulated expression of forkhead box O3a (FoxO3a) and mammalian target of rapamycin (mTOR). KPE attenuated inflammatory mediators (interleukin-6 (IL-6), IL-8, nuclear factor kappa B (NF-κB), and cyclooxygenase-2 (COX-2)) and increased the mRNA expression of PGC-1α, ERRα, NRF1, and Tfam, which modulate mitochondrial biogenesis and function. Consequently, reduced ATP levels and increased ROS level were also reversed by KPE treatment. In hairless mice, KPE inhibited wrinkle formation, skin atrophy, and loss of elasticity by increasing the collagen and elastic fibers. The results indicate that KPE prevents intrinsic aging process in hairless mice by inhibiting cellular senescence and mitochondrial dysfunction, suggesting its potential as a natural antiaging agent.

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