The Experts below are selected from a list of 327 Experts worldwide ranked by ideXlab platform
Abdul-kader Souid - One of the best experts on this subject based on the ideXlab platform.
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Zoledronic acid and bone Cellular Respiration.
Journal of Bone and Mineral Metabolism, 2017Co-Authors: Mohammed T. Alsamri, Suleiman Al-hammadi, Barira Islam, Abdul-kader SouidAbstract:Phosphorescence O2 analyzer was used to measure calvarial bone Cellular Respiration (Cellular mitochondrial O2 consumption) in Taylor Outbred mice in the presence and absence of zoledronic acid. This potent bisphosphonate inhibits osteoclast-mediated calcium resorption, and its effects on bone Respiration have not been previously investigated. The change of O2 concentration with time was measured in closed vials containing phosphate-buffered saline (PBS), 5 mM glucose and 5–25 mg calvarial bone fragments, and it was complex for t = 0–30 h. Cyanide (specific inhibitor of cytochrome oxidase) halted O2 consumption, confirming the oxidation occurred in the respiratory chain. Initial rate of Respiration was estimated from the zero-order plots d[O2]/dt for t = 0–4 h. For untreated specimens, the rate (mean ± SD) was 2.0 ± 1.2 µM O2 h−1 mg−1 (n = 6). This value was 7–10 times lower than that of other murine organs, but similar to that reported for rat and Guinea pig calvaria (averaging, 2.7 nmol O2 h−1 mg−1). The corresponding rate in the presence of 10–100 µM zoledronic acid was 2.7 ± 0.7 µM O2 h−1 mg−1 (n = 11), p = 0.216. The first-order plots ln ([O2] t ÷ [O2] t=0) versus time for t = 0–30 h were also used to compare treated and untreated specimens. The rate (h−1 mg−1 103) for specimens incubated in PBS without glucose was 1.3 ± 0.6 (n = 3, p = 0.007), in PBS + glucose it was 10.7 ± 6.9 (n = 10), in PBS + glucose + 10 µM zoledronic acid it was 12.1 ± 6.7 (n = 10, p = 0.579), in PBS + glucose + 20 µM zoledronic acid it was 12.9 ± 3.3 (n = 9, p = 0.356), and in PBS + glucose + 100 µM zoledronic acid it was 13.7 ± 7.7 (n = 9, p = 0.447). Thus, exposure to high-doses of zoledronic acid over several hours imposed a statistically insignificant increase in calvarial bone Cellular Respiration.
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The PI3Kδ inhibitor idelalisib suppresses liver and lung Cellular Respiration.
International journal of physiology pathophysiology and pharmacology, 2015Co-Authors: Suleiman Al Hammadi, Saeeda Almarzooqi, Dhanya Saraswathiamma, Hidaya Mohammed Abdul-kader, Abdul-kader SouidAbstract:Idelalisib (an inhibitor of phosphatidylinositol-3-kinase-delta) is approved for treatment of B-cell malignancies, with a Boxed Warning concerning potentially fatal hepatic, lung, and intestinal toxicities. The mechanisms of these tissue-specific adverse events have yet to be elucidated. This in vitro study investigated whether these effects could be attributed, at least in part, to altered Cellular bioenergetics. A phosphorescence analyzer was used to measure Cellular mitochondrial O2 consumption (kc , µM O2 min(-1) mg(-1)) in C57BL/6 mouse organs in the presence of 10 µM idelalisib or dimethyl-sulfoxide. Idelalisib significantly reduced the rate of Cellular Respiration in liver and lung fragments by 20% and 27%, respectively. Respiration in intestinal, thymic, and kidney fragments was unaffected. Idelalisib did not alter respiratory chain activities in mitochondria isolated from the liver and did not induce hepatocyte death. Thus, the drug mildly lowers liver and lung Cellular Respiration, an effect that may contribute to toxicities observed in these organs.
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The mTOR inhibitor sirolimus suppresses renal, hepatic, and cardiac tissue Cellular Respiration.
International Journal of Clinical and Experimental Pathology, 2015Co-Authors: Alia Albawardi, Saeeda Almarzooqi, Dhanya Saraswathiamma, Hidaya Mohammed Abdul-kader, Abdul-kader Souid, Ali S AlfazariAbstract:The purpose of this in vitro study was to develop a useful biomarker (e.g., Cellular Respiration, or mitochondrial O2 consumption) for measuring activities of mTOR inhibitors. It measured the effects of commonly used immunosuppressants (sirolimus - rapamycin, tacrolimus, and cyclosporine) on Cellular Respiration in target tissues (kidney, liver, and heart) from C57BL/6 mice. The mammalian target of rapamycin (mTOR), a serine/threonine kinase that supports nutrient-dependent cell growth and survival, is known to control energy conversion processes within the mitochondria. Consistently, inhibitors of mTOR (e.g., rapamycin, also known as sirolimus or Rapamune®) have been shown to impair mitochondrial function. Inhibitors of the calcium-dependent serine/threonine phosphatase calcineurin (e.g., tacrolimus and cyclosporine), on the other hand, strictly prevent lymphokine production leading to a reduced T-cell function. Sirolimus (10 μM) inhibited renal (22%, p = 0.002), hepatic (39%, p < 0.001), and cardiac (42%, p = 0.005) Cellular Respiration. Tacrolimus and cyclosporine had no or minimum effects on Cellular Respiration in these tissues. Thus, these results clearly demonstrate that impaired Cellular Respiration (bioenergetics) is a sensitive biomarker of the immunosuppressants that target mTOR.
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In vitro effects of platinum compounds on renal Cellular Respiration in mice.
International Journal of Clinical and Experimental Pathology, 2015Co-Authors: Saeeda-s Almarzooqi, Dhanya Saraswathiamma, Ali S Alfazari, Hidaya-m Abdul-kader, Alia-s Albawardi, Abdul-kader SouidAbstract:Background: Cisplatin, carboplatin and oxaliplatin are structurally-related compounds, which are commonly used in cancer therapy. Cisplatin (Platinol®) has Boxed Warning stating: “Cumulative renal toxicity associated with PLATINOL is severe”, while carboplatin and oxaliplatin are less nephrotoxic. These drugs form platinum adducts with Cellular DNA. Their bindings to Cellular thiols (e.g., glutathione and metallothionein) are known to contribute to drug resistance while thiol depletion augments platinum toxicity. Methods: Using phosphorescence oxygen analyzer, this study investigated the effects of platinum drugs on renal Cellular Respiration (mitochondrial O2 consumption) in the presence and absence of the thiol blocking agent N-ethylmaleimide (used here as a model for thiol depletion). Renal Cellular ATP was also determined. Kidney fragments from C57BL/6 mice were incubated at 37°C in Krebs-Henseleit buffer (gassed with 95% O2:5% CO2) with and without 100 μM platinum drug in the presence and absence of 100 μM N-ethylmaleimide for ≤ 6 h. Results: Platinum drugs alone had no effects on Cellular Respiration (P ≥ 0.143) or ATP (P ≥ 0.161). N-ethylmaleimide lowered Cellular Respiration (P ≤ 0.114) and ATP (P = 0.008). The combination of platinum drug and N-ethylmaleimide significantly lowered both Cellular Respiration (P ≤ 0.006) and ATP (P ≤ 0.003). Incubations with N-ethylmaleimide alone were associated with moderate-to-severe tubular necrosis. Incubations with cisplatin+N-ethylmaleimide vs. cisplatin alone produced similar severities of tubular necrosis. Tubular derangements were more prominent in carboplatin+N-ethylmaleimide vs. carboplatin alone and in oxaliplatin+N-ethylmaleimide vs. oxaliplatin alone. Conclusions: These results demonstrate the adverse events of thiol depletion on platinum-induced nephrotoxicities. The results suggest Cellular bioenergetics is a useful surrogate biomarker for assessing drug-induced nephrotoxicities.
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effects of selected inhibitors of protein kinases and phosphatases on Cellular Respiration an in vitro study
Journal of Clinical Toxicology, 2014Co-Authors: Saeeda Almarzooqi, Alia Albawardi, Dhanya Saraswathiamma, Ali S Alfazari, Hidaya Mohammed Abdulkader, Sami Shaban, Robert Mallon, Abdul-kader SouidAbstract:Inhibitors of protein kinases/phosphatases are known to alter Cellular metabolism. Effects of these rapidly identified small molecules on Cellular Respiration (mitochondrial O2 consumption) have not been adequately investigated, especially in healthy organs. This in vitro study measured Cellular Respiration in tissues from C57BL/6 mice with and without GSK2126458 (PI3K/mTOR inhibitor), BEZ235 (PI3K/mTOR inhibitor), GDC0980 (PI3K/mTOR inhibitor), GSK1120212 (trametinib, MEK inhibitor), sorafenib, regorafenib (multikinase inhibitors), and cyclosporine (calcineurin inhibitor). Cellular Respiration was measured by the phosphorescence oxygen analyzer, aided by the O2 probe Pd(II)-meso-tetra-(4-sulfonatophenyl)-tetrabenzoporphyrin. Cyanide inhibited O2 consumption, confirming the oxidation occurred in the respiratory chain. Renal Cellular Respiration decreased 26-34% in the presence of 10 μM GSK2126458 (p<0.001), 10 μM BEZ235 (p<0.001), or 1.0 μM GDC0980 (p<0.001). Liver Cellular Respiration decreased 20-32% with 10 μM GSK2126458 (p=0.048), 0.1 μM BEZ235 (p=0.028), or 0.1 μM GDC0980 (p=0.016). Heart Cellular Respiration decreased 19-27% with 10 μM GSK2126458 (p=0.078), 10 μM BEZ235 (p=0.040), or 10 μM GDC0980 (p=0.036). GSK1120212, sorafenib, regorafenib, and cyclosporine had no effects on Cellular Respiration. Thus, Cellular bioenergetics (the biochemical processes involved in energy conversion) is interconnected with PI3K/PTEN/Akt/mTOR; and inhibitors of this cascade impair Cellular Respiration. This biomarker (Cellular Respiration) senses the activity/toxicity of this class of molecularly targeted agents.
Monika Baj Krzyworzeka - One of the best experts on this subject based on the ideXlab platform.
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autologous tumor derived microvesicles influence gene expression profiles and enhance protumorigenic chemotactic potential signal transduction and Cellular Respiration in gastric cancer cells
International Journal of Oncology, 2019Co-Authors: Rafał Szatanek, Kazimierz Weglarczyk, Małgorzata Stec, Maciej Siedlar, Jaroslaw Baran, Magdalena Parlinska Wojtan, Monika Baj KrzyworzekaAbstract:Tumor‑derived microvesicles (TMVs) interact with a variety of different cell types within the immune system, including lymphocytes, monocytes, dendritic cells and tumor cells that they have originated from. In the present study, the effects of autologous‑TMVs (auto‑TMVs) on gene expression, chemotaxis, interCellular signaling and Cellular metabolism were examined in cells of the gastric cancer (GC) cell line 1415 (GC1415). The effects of auto‑TMVs on mRNA gene expression in GC1415 cells were assessed using pathway‑focused PCR arrays. A chemotaxis assay was performed using the HoloMonitor M4 System. Signaling pathways were evaluated using western blot analysis, and Cellular Respiration was measured using the Seahorse XF Cell Mito Stress Test. Exposure of the GC1415 cells to auto‑TMVs led to the overexpression (75 genes) and underexpression (96 genes) of genes that are associated with signal transduction, metabolism, chemotaxis, angiogenesis and metastasis. The auto‑TMVs were indicated to induce chemotaxis and activate the PI3K/AKT signaling pathway in GC1415 cells. However, the MAPK/ERK signaling pathway was not indicated to be activated. Furthermore, studies on Cellular Respiration in GC1415 cells exposed to auto‑TMVs demonstrated a metabolic shift to glycolysis. The results of the current study thus indicate that auto‑TMVs may exert an effect on tumor cell function.
Rafał Szatanek - One of the best experts on this subject based on the ideXlab platform.
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Autologous tumor‑derived microvesicles influence gene expression profiles and enhance protumorigenic chemotactic potential, signal transduction and Cellular Respiration in gastric cancer cells.
International Journal of Oncology, 2019Co-Authors: Rafał Szatanek, Kazimierz Weglarczyk, Małgorzata Stec, Jarosław Baran, Magdalena Parlinska‑wojtan, Maciej Siedlar, Monika Baj‑krzyworzekaAbstract:Tumor‑derived microvesicles (TMVs) interact with a variety of different cell types within the immune system, including lymphocytes, monocytes, dendritic cells and tumor cells that they have originated from. In the present study, the effects of autologous‑TMVs (auto‑TMVs) on gene expression, chemotaxis, interCellular signaling and Cellular metabolism were examined in cells of the gastric cancer (GC) cell line 1415 (GC1415). The effects of auto‑TMVs on mRNA gene expression in GC1415 cells were assessed using pathway‑focused PCR arrays. A chemotaxis assay was performed using the HoloMonitor M4 System. Signaling pathways were evaluated using western blot analysis, and Cellular Respiration was measured using the Seahorse XF Cell Mito Stress Test. Exposure of the GC1415 cells to auto‑TMVs led to the overexpression (75 genes) and underexpression (96 genes) of genes that are associated with signal transduction, metabolism, chemotaxis, angiogenesis and metastasis. The auto‑TMVs were indicated to induce chemotaxis and activate the PI3K/AKT signaling pathway in GC1415 cells. However, the MAPK/ERK signaling pathway was not indicated to be activated. Furthermore, studies on Cellular Respiration in GC1415 cells exposed to auto‑TMVs demonstrated a metabolic shift to glycolysis. The results of the current study thus indicate that auto‑TMVs may exert an effect on tumor cell function.
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autologous tumor derived microvesicles influence gene expression profiles and enhance protumorigenic chemotactic potential signal transduction and Cellular Respiration in gastric cancer cells
International Journal of Oncology, 2019Co-Authors: Rafał Szatanek, Kazimierz Weglarczyk, Małgorzata Stec, Maciej Siedlar, Jaroslaw Baran, Magdalena Parlinska Wojtan, Monika Baj KrzyworzekaAbstract:Tumor‑derived microvesicles (TMVs) interact with a variety of different cell types within the immune system, including lymphocytes, monocytes, dendritic cells and tumor cells that they have originated from. In the present study, the effects of autologous‑TMVs (auto‑TMVs) on gene expression, chemotaxis, interCellular signaling and Cellular metabolism were examined in cells of the gastric cancer (GC) cell line 1415 (GC1415). The effects of auto‑TMVs on mRNA gene expression in GC1415 cells were assessed using pathway‑focused PCR arrays. A chemotaxis assay was performed using the HoloMonitor M4 System. Signaling pathways were evaluated using western blot analysis, and Cellular Respiration was measured using the Seahorse XF Cell Mito Stress Test. Exposure of the GC1415 cells to auto‑TMVs led to the overexpression (75 genes) and underexpression (96 genes) of genes that are associated with signal transduction, metabolism, chemotaxis, angiogenesis and metastasis. The auto‑TMVs were indicated to induce chemotaxis and activate the PI3K/AKT signaling pathway in GC1415 cells. However, the MAPK/ERK signaling pathway was not indicated to be activated. Furthermore, studies on Cellular Respiration in GC1415 cells exposed to auto‑TMVs demonstrated a metabolic shift to glycolysis. The results of the current study thus indicate that auto‑TMVs may exert an effect on tumor cell function.
Naama Kanarek - One of the best experts on this subject based on the ideXlab platform.
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nadh ties one carbon metabolism to Cellular Respiration
Cell Metabolism, 2020Co-Authors: Adam G Maynard, Naama KanarekAbstract:In this issue of Cell Metabolism, Yang et al., 2020 report that serine is a source of mitochondrial NADH derived from one-carbon metabolism. Serine becomes a major source of NADH when Cellular Respiration is inhibited, and the un-utilized, accumulated NADH inhibits the TCA cycle and slows proliferation.
Toshiya Sakata - One of the best experts on this subject based on the ideXlab platform.
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Elucidation of interfacial pH behaviour at the cell/substrate nanogap for in situ monitoring of Cellular Respiration
Nanoscale, 2018Co-Authors: Hiroto Satake, Akiko Saito, Toshiya SakataAbstract:In situ monitoring of Cellular metabolism is useful for elucidating dynamic functions of living cells. In our previous studies, Cellular Respiration was continuously monitored as a change in pH at the cell/electrode nanoscale interface (i.e., interfacial pH) using an ion-sensitive field-effect transistor (ISFET). However, such interfacial pH behaviour on the nanoscale has not been confirmed using other methods such as fluorescence imaging. In this study, we have clarified the interfacial pH behaviour at a cell/substrate nanogap using a laser scanning confocal fluorescence microscope. The phospholipid fluorescein used as a pH indicator was fixed to the plasma membrane on the external side of a cell by inserting its lipophilic alkyl chain into the membrane, and used to observe the change in interfacial pH. As a result, hydrogen ions generated by Cellular Respiration were gradually accumulated at the cell/substrate nanogap, resulting in a decrease in pH. Moreover, the interfacial pH between the plasma membrane and the substrate became lower than the pH near the surface of cells not in contact with the substrate. The data obtained in this study support the idea that potentiometric ion sensors such as ISFETs can detect a Cellular-metabolism-induced change in pH at a cell/electrode nanogap in real time.
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elucidation of interfacial ph behaviour at the cell substrate nanogap for in situ monitoring of Cellular Respiration
Nanoscale, 2018Co-Authors: Hiroto Satake, Akiko Saito, Toshiya SakataAbstract:In situ monitoring of Cellular metabolism is useful for elucidating dynamic functions of living cells. In our previous studies, Cellular Respiration was continuously monitored as a change in pH at the cell/electrode nanoscale interface (i.e., interfacial pH) using an ion-sensitive field-effect transistor (ISFET). However, such interfacial pH behaviour on the nanoscale has not been confirmed using other methods such as fluorescence imaging. In this study, we have clarified the interfacial pH behaviour at a cell/substrate nanogap using a laser scanning confocal fluorescence microscope. The phospholipid fluorescein used as a pH indicator was fixed to the plasma membrane on the external side of a cell by inserting its lipophilic alkyl chain into the membrane, and used to observe the change in interfacial pH. As a result, hydrogen ions generated by Cellular Respiration were gradually accumulated at the cell/substrate nanogap, resulting in a decrease in pH. Moreover, the interfacial pH between the plasma membrane and the substrate became lower than the pH near the surface of cells not in contact with the substrate. The data obtained in this study support the idea that potentiometric ion sensors such as ISFETs can detect a Cellular-metabolism-induced change in pH at a cell/electrode nanogap in real time.