Mechanisms of ammonia and ammonium ion toxicity in animal cells: Transport across cell membranes

Martinelle, Kristina; Häggström, Lena

doi:10.1016/0168-1656(93)90148-g

Cited by 130 publications

(77 citation statements)

References 26 publications

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“…Ammonium is in contrast to the situation in animal cells (e. g. see [22]) and plants (e.g., [4,5]) not toxic for the studied model bacteria C. glutamicum, E. coli, and B. subtilis, even in molar concentrations. Because most bacteria prefer ammonium as nitrogen source and some species even produce ammonium, for example, rhizobia and cyanobacteria by N 2 -fixation and proteolytic clostridia by amino acid fermentation, we assume that ammonium resistance is a general phenomenon in bacteria.…”

Section: Discussionmentioning

confidence: 66%

Ammonium Toxicity in Bacteria

et al. 2006

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Abstract. Although an excellent nitrogen source for most bacteria, ammonium was-in analogy to plant and animal systems-assumed be detrimental to bacteria when present in high concentrations. In this study, we examined the effect of molar ammonium concentrations on different model bacteria, namely, Corynebacterium glutamicum, Escherichia coli, and Bacillus subtilis. The studied bacteria are highly resistant to ammonium. When growth was impaired upon addition of molar (NH 4 ) 2 SO 4 concentrations, this was not caused by an ammonium-specific effect but was due to an enhanced osmolarity or increased ionic strength of the medium. Therefore, it was concluded that ammonium is not detrimental to C. glutamicum and other bacteria even when present in molar concentrations.Ammonium (in this communication, the term ''ammonium'' is used in a general sense, including NH 4 + and NH 3 ; distinct ammonium species are indicated by chemical formula) is the preferred nitrogen source for most bacteria and fungi, and also plants acquire ammonium as a nitrogen source from the soil [35]. When present in high concentrations, diffusion of NH 3 , which is in equilibrium with NH 4 + , across the cytoplasmic membrane into the cell is sufficient to promote growth. In a situation of ammonium limitation, diffusion becomes negligible and special carriers are synthesized in bacteria, fungi, and plants (for a recent review, see [36]).However, ammonium is a paradoxical nutrient, because it is notorious for its cytotoxic effects. Furthermore, active transport of ammonium can to lead to a harmful energy-wasting futile cycling when accumulated ammonium diffuses across the cytoplasmic membrane back into the medium. Sensitivity to ammonium is discussed to be a universal phenomenon; however, it is well investigated only in plant and animal systems [36], whereas the situation in bacteria is less clear.

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Section: Discussionmentioning

confidence: 66%

Ammonium Toxicity in Bacteria

et al. 2006

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“…All data documenting ammonia toxicity stem from studies where different amounts of ammonia were added to the media. However, it has been discussed that the physiological consequences of adding ammonia extracellularly to the medium are very different to those resulting from ammonia produced intracellularly (Martinelle and Haggstrom 1993). All available publications on toxicity of ammonia report its negative effect in doses above 1-2 mM (cell viability) and above 10 mM (virus growth) with significant differences from study to study regarding the cell type or virus strain (Schneider et al 1996).…”

Section: Discussionmentioning

confidence: 93%

Stability of Minimum Essential Medium functionality despite l-glutamine decomposition

et al. 2015

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L-Glutamine (L-Gln) instability in liquid media is a well-known fact. Also, negative effect of ammonia, one of the L-Gln degradation products, on viability of many cell cultures and on replication of different viruses has been described. However, negative effects of ammonia have been reported in doses excessively exceeding those that could be generated in regularly used liquid culture media due to spontaneous L-Gln breakdown (below 2 mM). Traditional virus vaccine production processes have been established and registered involving L-Gln containing media use. Eventual culture media replacement in the regular production process belongs to the major regulative changes that require substantial financial expenses. The aim of this study was to evaluate the effect of storage of Minimum Essential Media with Hanks salts on their relevant biological functions during virus vaccine production process in relation to L-Gln decrease. Our results show a cell type dependent effect of spontaneous L-Gln degradation during medium storage. They also suggest that for cell cultures used in measles, mumps, and rubella virus production the media retain their functionality in respect to cell viability or virus growth over a certain time window despite L-Gln degradation.

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“…The main byproduct of the glutamine metabolism, released to the medium, is the ammonium ion, which is an important inhibitor of cell growth ( Glacken MW. 1998;Martinelle K, Haggstrom L. 1993;Xie L, Wang DI. 1994 ).…”

Section: Discussionmentioning

confidence: 99%

Parameters for MDBK cell growth on microcarriers and BoHV-1 virus production

Freitas¹,

Mozzer²,

Freitas³

et al. 2017

VR&R

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Bovine herpes virus 1 (BoHV-1) is an important veterinary agent , which causes infectious bovine rhinotracheitis. This disease affects the respiratory tract or genitals, causing weight loss, reduced milk production and abortion. Several vaccines against BoHV-1 have been developed. In this paper, we study the parameters for MDBK growth on microcarriers (Cytodex 1) and for BoHV-1 virus production. The cell culture attached to microcarriers is an efficient method to enlarge the surface of cell growth and for large-scale cell production. Our studies reveal that MDBK adhered to MCs in 30 minutes and that initial agitation of culture did not influence on the efficiency of adhesion or cell growth. In our experiments, we detected no relevant influence of agitation on initial cell adhesion of MDBK to MCs. The maximum cell yield was similar to all initial conditions of agitation studied. The maximum yield obtained in culture started with 15, 20 and 30 cells / MC, was respectively.8.7 x105, 9.3 x105 and 9.8 x105 cells / ml . The cellular distribution on the MCs at the beginning of the culture was more heterogeneous in higher initial densities. After three medium exchanges during MDBK cell culture, the increase in the final yield was 100% higher than that from culture performed without medium change (0.93 x 106 cells / mL). Replacing 50% of the culture medium with fresh medium after 24 hours of growth, the concentration of glucose (5 mM) and glutamine (1.8 mM) were almost completely restored. In these studies, BoHV-1 infections of MDBK were performed after 48, 72 and 86 hours with daily exchanges of 50% of the medium. The increase in viral titer was proportional to the number of viable cells present at the time of infection. The best result of BoHV-1 production was achieved when the infection was performed from 86 hours of cell culture, reaching about 3.7 x108 (TCID50/ml) after 24-48 hours of infection, being on average four times higher when compared to the culture in which the infection was performed with 48 hours of culture and approximately 2 times greater than the crop whose infection occurred after 72 hours of culture. The best yields are obtained when viral infections were performed on cultures with higher cell densities. The best result for the production of BoHV-1 occurred with 10 MOI, 48 hours after infection, which yield was 24 and 41% superior to the MOI 0.1 and 1, respectively.

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Mechanisms of ammonia and ammonium ion toxicity in animal cells: Transport across cell membranes

Cited by 130 publications

References 26 publications

Ammonium Toxicity in Bacteria

Ammonium Toxicity in Bacteria

Stability of Minimum Essential Medium functionality despite l-glutamine decomposition

Parameters for MDBK cell growth on microcarriers and BoHV-1 virus production

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