Intracellular acidification

Simultaneous and continuous measurements of extracellular pH, potassium K+, and lactate in an ischemic heart were carried out to study lactic acid production, intracellular acidification, and cellular K+ loss and their quantitative relationships [6, 7], The pH sensor was fabricated on a flexible kapton substrate and the pH sensitive iridium oxide layer was electrodeposited on a planar platinum electrode. Antimony-based pH electrodes have also been used for the measurement of myocardial pH in addition to their application in esophageal acid reflux detection. 

Contribution of anion transporters to the acidosis-induced swelling and intracellular acidification of glial cells. J Neurochem 75 125-132. 

Liu S, Tafet S, Stoner L, Delmar M, Vallano ML, Jalife J A structural basis for the unequal sensitivity of the major cardiac and liver gap junctions to intracellular acidification The carboxy tail length. Biophys J 1993 64 1422-1433. 

ATPase. In these cells, the system can still be activated by an intracellular acidification, and hence contributes to the protection of cells against acute acid loads. 

Figure 2. The role of the Na+/H+ exchanger in pHi regulation. A steady state pHi is attained when the rate of cellular acidification is equal to the rate of cellular alkalinization. In resting cells, the rate of intracellular acidification is low and low activity of the Na+/H+ exchanger is sufficient to maintain a stable pHi. An acute acid load activates H+ efflux, thus allowing cel Is to recover their basal pHi. When, however, cells face chronic intracellular acidification (for instance as a result of an increased metabolic activity), a lower steady state is attained. Sensitization of the Na+/H+ exchanger to H+ following its phosphorylation increases H+ efflux and provides a mechanism for maintaining a stable pHi in spite of the increased acid load.

The involvement of CAD as the endonuclease in apoptosis contradicts previous suggestions of other endonucleases involved in apoptosis. CAD is a Ca2+-independent endonuclease whereas many groups have implicated a Ca2+-dependent endonuclease in apoptosis [65-69], However, we have presented considerable evidence that Ca2+ is not required for DNA digestion, and furthermore, that depleting Ca2+ is a stimulus for DNA digestion [70][71], We have implicated deoxyribonuclease II (DNase II) as an alternate endonuclease involved in apoptosis [72], DNase II requires low pH for activity, and we have established that intracellular acidification is a common occurrence in apoptosis [73-76]. Intracellular acidification is a conse-... 

During the investigation of the calcium entry pathways activated by palytoxin in cultured nemons, we observed that the toxin caused a rapid intracellular acidification. Since pH plays a pivotal role in signal transdnction in several cell models, we have examined the effect of palytoxin on intracellnlar pH. Previons stndies have shown that palytoxin indnces cell acidification in embryonic chick ventric-nlar cells (Frelin et al. 1990) and osteoblasts (Momoe and Tashjian 1995). In primary cultures of CGC, palytoxin from 0.1 to 50 nM indnced a dose-dependent intracellnlar acidification (Fig. 6.4). As in the case of calcinm increase indnced by palytoxin, the pH decrease was significant at palytoxin concentrations as low as 1 nM (p < 0.01). Maximnm intracellnlar acidification was observed for palytoxin concentrations of 10, 25, and 50 nM (p < 0.001). At these concentrations, palytoxin decreased pH by 0.6 nnits. The effect of palytoxin on pH was immediate after addition of the toxin. 

Figure 6.4. Intracellular acidification produced by palytoxin in cultured cerebellar neurons.

In our experimental model, the palytoxin-induced cellular acidification was completely prevented by inhibitors of the plasma-membrane calcium ATPase, including orthovanadate, lanthanum and an extracellular pH of 8.5. Om results therefore indicate that the plasma-membrane calcium ATPase is involved in the palytoxin-induced intracellular acidification in primary cultures of cerebellar granule cells. We suggest that the increase in intracellular calcium evoked by palytoxin will activate the calcium extrasion mechanisms through the calcium pump, which, in turn, will decrease intracellular pH through countertransport of H ions (Vale-Gonzalez et al. 2007). 

Wang, G.J., Randall, R.D., Thayer, S.A. (1994). Glutamate-induced intracellular acidification of cultured hippocampal neurons demonstrates altered energy metabolism resulting from Ca loads. J. Neurophysiol. 72 2563-9. 

LeBoeuf RA, Lin P, Kerchaert G, Gruen-steinE. 1992. Intracellular acidification is associated with enhanced morphological transformation in Syrian hamster embryo cells. Cancer Res. 32 144 48... 

Acetic acid is lipid soluble and able to rapidly diffuse through the plasma membrane, a factor that has a dramatic effect on the pH, of a cell (Greenacre et al., 2003). Intracellular acidification may, however, play a role in acids with short aliphatic chains (such as acetic acid), and much higher concentrations (20-80 mM) are needed for growth inhibition (Hazan, Levine, and Abeliovich, 2004). 

Plumridge, A., Hesse, S.J., Watson, A.J., Lowe, K.C., Stratford, M., and Archer, D.B. 2004. The weak acid preservative sorbic acid inhibits conidial germination and mycelial growth of Aspergillus niger through intracellular acidification. Applied and Environmental Microbiology 70 3506-3511. 

It was initially speculated that the antifungal action of organic acids is based on intracellular acidification, because this inhibits glycolysis (Leyva and Peinado, 2005). However, results obtained with exponentially growing cells, both in batch (Warth, 1991) as well as chemostat cultures (Verduyn et al., 1990), showed that glycolysis was enhanced when cells were cultured in the presence of sublethal concentrations of organic acids. It was also detected that phosphofructokinase activity was not inhibited (Warth, 1991). 

Ramos, S.M., Balbin, M., Raposo, E., and Pardo, L.A. 1989. The mechanism of intracellular acidification induced by glucose in Saccharomyces cerevisiae. Journal of General Microbiology 135 2413-2422. 

Xiong Z-Q, Saggau P, Stringer J. Activity-dependent intracellular acidification correlates with the duration of seizure activity. J Neurosci 2000 20 1290-1296. 

Liu, D., Martino, G., Thangaraju, M Sharma, M., Halwani, F., Shen, S. H et al. (2000) Caspase-8-mediated intracellular acidification precedes mitochondrial dysfunction in somatostatin-induced apoptosis. J. Biol. Chem. 275(13), 9244-9250. 

Khodorov BI (1985) Batrachotoxin as a tool to study voltage-sensitive sodium channels of excitable membranes. Prog Biophys Mol Biol 45 57-148 Khodorov BI, Valkina O, Turovetsky V (1994) Mechanisms of stimulus-evoked intracellular acidification in frog nerve fibres. FEES Lett 341 125-127 Khodorov BI, Zaborovskaya LD (1983) Blockade of sodium and potassium channels in the node of Ranvier by ajmaline and N-propyl ajmaline. Gen Physiol Biophys 2 233-268... 

In primary cultures of cerebellar neurons, palytoxin also caused a rapid intracellular acidification. Previous work had shown palytoxin-induced intracellular acidification in chick ventricular cells and osteoblasts. The acidification induced by the toxin was reported to be dependent on the opening of proton-conductive pathways in the plasma membrane or to be a secondary effect of the interaction of the toxin with the sodium pump, respectively. In primary neuronal cultures, palytoxin caused a fast and irreversible intracellular acidification. The decrease in intracellular pH (pHj) caused by palytoxin was already maximal at toxin concentrations of 1 nM (Figure 31.4) at this concentration, palytoxin decreased intracellular pH by 0.6 units. 

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