scholarly journals Oxidative Phosphorylation Promotes Primary Melanoma Invasion

2020 ◽  
Vol 190 (5) ◽  
pp. 1108-1117 ◽  
Author(s):  
Amel Salhi ◽  
Alexander C. Jordan ◽  
Irineu I. Bochaca ◽  
Allison Izsak ◽  
Farbod Darvishian ◽  
...  
Keyword(s):  
Oxidative Phosphorylation ◽  
Primary Melanoma ◽  
Melanoma Invasion

scholarly journals Ultraviolet light-induced collagen degradation inhibits melanoma invasion

2021 ◽  
Author(s):  
Timothy Budden ◽  
Caroline Gaudy ◽  
Andrew Porter ◽  
Emily Kay ◽  
Shilpa Gurung ◽  
...  
Keyword(s):  
Cell Invasion ◽  
Older Patients ◽  
Dermal Fibroblast ◽  
Single Cells ◽  
Primary Melanoma ◽  
The Elderly ◽  
Invasive Front ◽  
Melanoma Invasion ◽  
Local Levels

AbstractUltraviolet radiation (UVR) increases the incidence of cutaneous melanoma1–4. The ageing, sun-exposed dermis accumulates UVR damage5, and older patients develop more melanomas at UVR-exposed sites4,6,7. As fibroblasts are functionally heterogeneous and play key roles in the stromal contribution to cancer8,9, we asked whether UVR modifies dermal fibroblast function. Here we confirmed the expression of collagen-cleaving matrix metalloprotein-1 (MMP1) by UVR-damaged fibroblasts was persistently upregulated to reduce local levels of collagen 1 (COL1A1), and found dermal COL1A1 degradation by MMP1 decreased melanoma invasion. Conversely, we show inhibiting extracellular matrix degradation and MMP1 expression restored melanoma invasion to UVR damaged dermis. We confirmed in vitro findings in a cohort of primary cutaneous melanomas of aged humans, showing more cancer cells invade as single cells at the invasive front of melanomas expressing and depositing more collagen. We found collagen and single melanoma cell invasion are robust predictors of poor melanoma-specific survival. These data indicate melanomas arising over UVR-damaged, collagen-poor skin of the elderly are less invasive, and this reduced invasion improves survival. Consequently, although UVR increases tumour incidence, it delays primary melanoma invasion by degrading collagen. However, we show melanoma-associated fibroblasts can restore invasion in low-collagen primary tumours by increasing collagen synthesis. Finally, we demonstrate high COL1A1 gene expression is a biomarker of poor outcome across a broad range of primary cancers.

Dependence of Platelet Adenyl Cyclase System on Oxidative Phosphorylation

1975 ◽  
Vol 34 (01) ◽  
pp. 042-049 ◽  
Author(s):  
Shuichi Hashimoto ◽  
Sachiko Shibata ◽  
Bokro Kobayashi
Keyword(s):  
Cyclic Amp ◽  
Oxidative Phosphorylation ◽  
Sodium Succinate ◽  
Potassium Cyanide ◽  
Adenyl Cyclase ◽  
Mitochondrial Oxidative Phosphorylation ◽  
Adenyl Cyclase Activity ◽  
Intact Rabbit ◽  
Adenyl Cyclase System ◽  
Cyclic Amp Synthesis

SummaryThe radioactive adenosine 3′,5′-monophosphate (cyclic AMP) level derived from 8-14C adenine in intact rabbit platelets decreased in the presence of mitochondrial inhibitor (potassium cyanide) or uncoupler (sodium azide), and markedly increased by the addition of NaF, monoiodoacetic acid (MIA), or 2-deoxy-D-glucose. The stimulative effect of the glycolytic inhibitors was distinctly enhanced by the simultaneous addition of sodium succinate. MIA did neither directly stimulate the adenyl cyclase activity nor inhibit the phosphodiesterase activity. These results suggest that cyclic AMP synthesis in platelets is closely linked to mitochondrial oxidative phosphorylation.

Low melatonin as a contributor to SARS-CoV-2 disease

2020 ◽  
Vol 3 (4) ◽  
pp. 558-576
Author(s):  
Seithikurippu R Pandi-Perumal ◽  
Daniel P Cardinali ◽  
Russel J Reiter ◽  
Gregory M Brown
Keyword(s):  
Reactive Oxygen Species ◽  
Oxidative Phosphorylation ◽  
Pineal Gland ◽  
Oxygen Species ◽  
Cytokine Storm ◽  
Major Site ◽  
Immune Modulator ◽  
Inflammatory Agent ◽  
Site Of Action ◽  
Extrapineal Melatonin

That the pineal gland is a source of melatonin is widely known; however, by comparison, few know of the much larger pool of extrapineal melatonin. That pool is widely distributed in all animals, including those that do not have a pineal gland, e.g., insects.  Extrapineal melatonin is not released into the blood but is used locally to function as an antioxidant, anti-inflammatory agent, etc. A major site of action of peripherally-produced melatonin is the mitochondria where it neutralizes reactive oxygen species (ROS) that are generated during oxidative phosphorylation. Its role also includes major actions as an immune modulator reducing overreactions to foreign agents while simultaneously boosting immune processes. During a pandemic such as coronavirus disease 2019 (COVID-19), caused by the virus SARS-CoV-2, melatonin is capable of suppressing the damage inflicted by the cytokine storm. The implications of melatonin in susceptibility and treatment of COVID-19 disease are discussed. 

249-LB: Effects of Oxidative Phosphorylation Complex Defects on Beta-Cell Biology

Diabetes ◽  
2020 ◽  
Vol 69 (Supplement 1) ◽  
pp. 249-LB
Author(s):  
ANNA L. LANG ◽  
ALEJANDRO CAICEDO
Keyword(s):  
Oxidative Phosphorylation ◽  
Beta Cell ◽  
Cell Biology
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