Study of fibroblast spreading: pH dependence, involvement of the Na+H+-antiporter and PKC

Novikova, Irina; Muravyeva, O. V.; Cragoe, E. J.; Margolis, Leonid

doi:10.1016/0167-4889(93)90203-2

Cited by 5 publications

(2 citation statements)

References 12 publications

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“…Our finding that higher pH promotes Mk apoptosis is consistent with a previous report [21] that high pH promotes T cell apoptosis. These effects of pH on apoptosis are somehow unexpected in view of the previously established relationship between apoptosis and low intracellular pH (pH i ) [29–, 31] and the generally accepted relationship between pH i and culture pH [32]. Indeed, it was reported that protection against apoptosis by overexpression of antiapoptotic proteins, such as Bcl‐2 and v‐Abl, in hematopoietic cells was accompanied by prevention of a decrease in pH i [30,, 31].…”

Section: Discussionmentioning

confidence: 99%

Higher pH Promotes Megakaryocytic Maturation and Apoptosis

2002

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Megakaryocytic (Mk) cells mature adjacent to bone marrow (BM) sinus walls and subsequently release platelets within the sinusoidal space or in lung capillaries. In contrast, primitive stem and Mk progenitor cells reside the furthest away from the BM sinus walls. The existence of pH gradients in the BM raises the question of whether pH affects Mk maturation and differentiation. We generated Mk cells from peripheral blood CD34 + cells in a serum-free medium at different pH levels (7.2, 7.4, and 7.6) and found that higher pH resulted in an earlier and higher polyploidization of CD41 + Mk cells and an earlier onset of Mk-cell apoptosis. The peak day of high ploidy was correlated well with the onset day of Mk apoptosis, thus suggesting that a decline in the fraction of high-ploidy Mk cells at the late culture stage is caused by Mk-cell apoptosis. We further explored the relationship between Mk-cell maturation and apoptosis by employing an antiapoptotic agent Z-Val-AlaAsp(Ome)-FMK (zVAD). Addition of zVAD led to an average 30% higher and 2.8-day delayed polyploidization, while apoptosis was delayed by 2.4 days. Faster depletion of CD34 + cells and an earlier peak in the fraction of larger colony-forming Mk cells (BFU-Mks) were also observed at higher pH. Taken together, these data suggest that higher pH promotes Mk-cell differentiation, maturation, and apoptosis.

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Section: Discussionmentioning

confidence: 99%

Higher pH Promotes Megakaryocytic Maturation and Apoptosis

2002

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“…All of which raises pH and stimulate glycolysis and cancer metabolism (Table 2). These relationships were discovered during and after the 1980s, well after Warburg's death [12,14,[17][18][19][20][21][22][23][24][25][26][27].…”

Section: Why Warburg Was Right and Wrong At The Same Timementioning

confidence: 99%

The Prime and Integral Cause of Cancer in the Post-Warburg Era

Harguindey¹,

Reshkin

Alfarouk³

2023

Cancers

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Back to beginnings. A century ago, Otto Warburg published that aerobic glycolysis and the respiratory impairment of cells were the prime cause of cancer, a phenomenon that since then has been known as “the Warburg effect”. In his early studies, Warburg looked at the effects of hydrogen ions (H+), on glycolysis in anaerobic conditions, as well as of bicarbonate and glucose. He found that gassing with CO2 led to the acidification of the solutions, resulting in decreased rates of glycolysis. It appears that Warburg first interpreted the role of pH on glycolysis as a secondary phenomenon, a side effect that was there just to compensate for the effect of bicarbonate. However, later on, while talking about glycolysis in a seminar at the Rockefeller Foundation, he said: “Special attention should be drawn to the remarkable influence of the bicarbonate…”. Departing from the very beginnings of this metabolic cancer research in the 1920s, our perspective advances an analytic as well as the synthetic approach to the new “pH-related paradigm of cancer”, while at the same time addressing the most fundamental and recent changing concepts in cancer metabolic etiology and its potential therapeutic implications.

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Inhibition of the Na+/H+ antiporter suppresses IL-12 p40 production by mouse macrophages

Németh¹,

Mabley

Deitch³

et al. 2001

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

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The amiloride-inhibitable Na(+)/H(+) antiporter plays an important role in macrophage activation. The intracellular pathways leading to interleukin (IL)-12 p40 production by activated macrophages are incompletely understood. In the present study, we examined the contribution of the Na(+)/H(+) antiporter to the production of IL-12 p40. Amiloride or its analogs decreased the production of IL-12 p40 in macrophages stimulated with bacterial lipopolysaccharide and interferon-gamma. The order of potency of amiloride analogs was consistent with the proposition that the effect of amiloride is mediated by the inhibition of the Na(+)/H(+) antiporter. The effect of amiloride was post-transcriptional, as IL-12 p40 mRNA levels induced by lipopolysaccharide and interferon-gamma were not affected by this inhibitor. Furthermore, the inhibitory effect of amiloride on IL-12 p40 production was not a result of interference with the activation of the p38 and p42/44 mitogen-activated protein kinases or c-Jun kinase. In summary, the production of IL-12 p40 requires a functional Na(+)/H(+) antiporter.

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Study of fibroblast spreading: pH dependence, involvement of the Na+H+-antiporter and PKC

Cited by 5 publications

References 12 publications

Higher pH Promotes Megakaryocytic Maturation and Apoptosis

Higher pH Promotes Megakaryocytic Maturation and Apoptosis

The Prime and Integral Cause of Cancer in the Post-Warburg Era

Inhibition of the Na+/H+ antiporter suppresses IL-12 p40 production by mouse macrophages

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