Explore chapters and articles related to this topic
Bioenergetics
Published in Michael H. Stone, Timothy J. Suchomel, W. Guy Hornsby, John P. Wagle, Aaron J. Cunanan, Strength and Conditioning in Sports, 2023
Michael H. Stone, Timothy J. Suchomel, W. Guy Hornsby, John P. Wagle, Aaron J. Cunanan
It appears that lactic acid may play a role in muscle and whole-body fatigue as a result of several possible mechanisms (278) and is likely the primary means of acidification during intense exercise. Thus, it is imperative to ameliorate lactic acid production or at least the potential negative effects produced by its production. One mechanism is to convert lactic acid to lactate.
Transformin Growth Factor-β
Published in Jason Kelley, Cytokines of the Lung, 2022
The anchorage-independent growth of NRK(49F) as target cells is the now classic bioassay in which TGF-β induces a transformed phenotype in soft agar. Visible colony formation in soft agar can be determined after 12–14 days of growth. The number of colonies formed is quantitated with an image analyzer system. It is essential that unknown biological samples to be tested be exposed to acid and then neutralized to activate latent forms of TGF-β before assay. Acid-treated and untreated samples are tested simultaneously to assure the effect of acidification. It has been suggested that cell density is an important determinant of responsiveness of cell-based bioassays to TGF-β and other cytokines (Rizzino et al., 1988). However, this does not appear to be true when the amount of cytokine tested is quantitated on a per cell basis (Battegay et al., 1990).
Biochemical Contributors to Exercise Fatigue
Published in Peter M. Tiidus, Rebecca E. K. MacPherson, Paul J. LeBlanc, Andrea R. Josse, The Routledge Handbook on Biochemistry of Exercise, 2020
Arthur J. Cheng, Maja Schlittler, Håkan Westerblad
Repeated depolarization of the sarcolemma causes an increase in extracellular K+ (K+o) that is regarded as a potential cause of fatigue. During exercise of increasing intensity in humans, an elevation in blood plasma K+o of up to 8 mM has been observed, and local concentrations surrounding muscle fibres may even reach 15 mM (59). When resting muscle fibres are exposed to such elevations of K+o, the resulting depolarization will inactivate the voltage-gated Na+ channels whereby action potential generation and propagation, especially into the t-tubular system, will be impaired, resulting in decreased SR Ca2+ release and reduced force production (58). Lactate and H+ are also produced during intense exercise requiring anaerobic metabolism, that is, under the same exercise conditions that cause increased K+o. Intriguingly, the ensuing intracellular acidosis decreases the sarcolemmal chloride ion conductance, which facilitates action potential propagation into the t-tubular system, and SR Ca2+ release is better maintained (63, 64). Thus, an intracellular acidification due to increased anaerobic metabolism may actually counteract, or even prevent, a fatigue-induced decline in force due to impaired action potential propagation.
Caudatin blocks the proliferation, stemness and glycolysis of non-small cell lung cancer cells through the Raf/MEK/ERK pathway
Published in Pharmaceutical Biology, 2022
Juan Hou, Qing Chen, Yufeng Huang, Zhiwei Wu, De Ma
Tumour cells have the characteristics of rapid proliferation, during which a large amount of energy is consumed rapidly. In the 1920s, Otto Warburg found that glycolysis was an important energy source for the rapid proliferation tumour cells, which is also called as Warburg’s effect (Liberti and Locasale 2016). Warburg effect is manifested as notably elevated glucose uptake, lactate production and ATP production in tumour cells. Lactic acid produced in the process of glycolysis is conducive to the growth of tumour cells (Sun S et al. 2017). Elevated lactic acid production promotes the angiogenesis, migration, prognosis and recurrence of tumour (Colegio 2016). Thus, targeting lactate metabolism is a promising and effective approach for cancer treatment (Doherty and Cleveland 2013). In our study, glucose uptake, lactic acid production and ATP level in H1299 and H520 cells were sharply decreased by caudatin treatment. GLUT1, HK2, PKM2 and LDHA are all glycolysis related genes (Liu R et al. 2019). Wu et al. (2020) reported that inhibition of key glycolytic genes blocked the progression of gastric cancer. In the present study, the expression of HK2 and LDHA was also decreased with increasing concentration of caudatin, indicating that caudatin effectively suppressed the proliferation of LSCC cells by inhibiting glycolysis. Extracellular acidification rate is an important indicator of the metabolism in cells (Villani et al. 2016). In our study, caudatin substantially decreased the level of ECAR, which indirectly reflected the glycolysis rate. In general, caudatin effectively weakened glycolysis in lung cancer cells.
Inhibitory effect of roburic acid in combination with docetaxel on human prostate cancer cells
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2022
Xiao Wang, Xu Xuetao, Mengshuo Wu, Panpan Wu, Zhaojun Sheng, Wenfeng Liu, Yan-Yan Ma, Den-Gao Zhao, Kun Zhang, Dongli Li, Xi Zheng, Susan Goodin
It is well known that the Warburg effect leads tumours to become acidic, and the acidic extracellular pH is a well recognised feature of tumour environment18. The tumour microenvironment acidification is a real phenotype that bursts the malignant behaviour of virtually all tumours, including prostate cancer19. Acidic tumour microenvironment increases tumour invasion, metastasis and chemotherapeutic drug resistance19. Interestingly, tissue acidification is common to type II diabetes as well20, suggesting that microenvironmental acidity is a common pathway of many human pathologies. Therefore, it is important to determine the activities of potential new anticancer compounds such as roburic acid in buffered pH and low pH conditions. Moreover, many laboratory-based and clinical studies have demonstrated that tumour acidity decreased the efficacy of chemotherapeutic agents, and antiacidic drugs such as proton pump inhibitors (PPIs) improved the effectiveness of anticancer therapies21–34. Combined potential new anticancer agents with PPIs is highly relevant for developing effective anticancer combination therapies.
Study logistics that can impact medical countermeasure efficacy testing in mouse models of radiation injury
Published in International Journal of Radiation Biology, 2021
Andrea L. DiCarlo, Zulmarie Perez Horta, Carmen I. Rios, Merriline M. Satyamitra, Lanyn P. Taliaferro, David R. Cassatt
In addition to considerations surrounding selection of feed, sites may also vary in the water provided to the animals. Water acidification (pH 2.5–3.0) has been one method used by many animal care facilities to reduce bacterial load in water bottles. Other sites may use an automatic watering system without additional acid treatment, rather than static bottles filled with acidified water. Researchers (Langgartner et al. 2017) tested acidified water vs. normal tap water in mice and found that water acidification altered thymus and adrenal weights. In addition, in a non-obese diabetic mouse model, water acidification was associated with reduced gut flora diversity (Sofi et al. 2014). It is not clear if there is a best system for radiation studies, but water treatment should be considered a variable, and if possible, tested.