Adaptive respiratory response of rat pancreatic acinar cells to mitochondrial membrane depolarization
The dependence of uncoupled respiratory capacity of intact pancreatic acini on oxidative substrate supply and functional cell state has not yet been studied in detail. In this study, the respiratory responses of isolated pancreatic acini to FCCP were measured with Clark electrode and mitochondrial m...
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| Format: | Article |
| Language: | English |
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National Academy of Sciences of Ukraine, Palladin Institute of Biochemistry
2019-05-01
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| Series: | The Ukrainian Biochemical Journal |
| Subjects: | |
| Online Access: | http://ukrbiochemjournal.org/wp-content/uploads/2019/05/Manko_3_19.pdf |
| _version_ | 1797428323302768640 |
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| author | B. O. Manko O. O. Bilonoha V. V. Manko |
| author_facet | B. O. Manko O. O. Bilonoha V. V. Manko |
| author_sort | B. O. Manko |
| collection | DOAJ |
| description | The dependence of uncoupled respiratory capacity of intact pancreatic acini on oxidative substrate supply and functional cell state has not yet been studied in detail. In this study, the respiratory responses of isolated pancreatic acini to FCCP were measured with Clark electrode and mitochondrial membrane potential was assessed with rhodamine123 fluorescence. The response of acini to FCCP was characterized with maximal uncoupled respiration rate, optimal FCCP concentration, respiration acceleration and deceleration. Maximal uncoupled respiration rate substantially increased upon the oxidation of glucose + glutamine (3.03 ± 0.54 r.u.), glucose + glutamine + pyruvate (2.82 ± 0.51 r.u.), glucose + isocitrate (2.71 ± 0.33 r.u.), glucose + malate (2.75 ± 0.38 r.u.), glucose + monomethyl-succinate (2.64 ± 0.42 r.u.) or glucose + dimethyl-α-ketoglutarate (2.36 ± 0.33 r.u.) comparing to glucose alone (1.73–2.02 r.u.) or no substrate (1.76 ± 0.33 r.u.). The optimal FCCP concentration was the highest (1.75 μM) upon glucose + glutamine + pyruvate combination and the lowest (0.5 μM) upon glutamate, combinations of glucose with isocitrate, malate, succinate or α-ketoglutarate. Respiration acceleration after FCCP application was the highest with dimethyl-α-ketoglutarate. Following the peak respiration, time-dependent deceleration was observed. It increased with FCCP concentration and depended on oxidative substrate type. Deceleration was the highest upon malate or isocitrate oxidation but was not observed in case of glutamine or dimethyl-α-ketoglutarate oxidation. Pyruvate alone or in combination with glutamine and glucose significantly decreased the depolarizing effect of FCCP on mitochondrial membrane potential and increased respiration elasticity coefficient with respect to the membrane potential change. Thus, in pancreatic acinar cells, the combination of pyruvate, glutamine and glucose enables the optimal adaptive respiratory response to membrane depolarization. |
| first_indexed | 2024-03-09T08:56:22Z |
| format | Article |
| id | doaj.art-959f9132610340dfb676646f869e8297 |
| institution | Directory Open Access Journal |
| issn | 2409-4943 2413-5003 |
| language | English |
| last_indexed | 2024-03-09T08:56:22Z |
| publishDate | 2019-05-01 |
| publisher | National Academy of Sciences of Ukraine, Palladin Institute of Biochemistry |
| record_format | Article |
| series | The Ukrainian Biochemical Journal |
| spelling | doaj.art-959f9132610340dfb676646f869e82972023-12-02T12:56:57ZengNational Academy of Sciences of Ukraine, Palladin Institute of BiochemistryThe Ukrainian Biochemical Journal2409-49432413-50032019-05-01913344510.15407/ubj91.03.034Adaptive respiratory response of rat pancreatic acinar cells to mitochondrial membrane depolarizationB. O. Manko0O. O. Bilonoha1 V. V. Manko2Ivan Franko National University of Lviv, UkraineIvan Franko National University of Lviv, UkraineIvan Franko National University of Lviv, UkraineThe dependence of uncoupled respiratory capacity of intact pancreatic acini on oxidative substrate supply and functional cell state has not yet been studied in detail. In this study, the respiratory responses of isolated pancreatic acini to FCCP were measured with Clark electrode and mitochondrial membrane potential was assessed with rhodamine123 fluorescence. The response of acini to FCCP was characterized with maximal uncoupled respiration rate, optimal FCCP concentration, respiration acceleration and deceleration. Maximal uncoupled respiration rate substantially increased upon the oxidation of glucose + glutamine (3.03 ± 0.54 r.u.), glucose + glutamine + pyruvate (2.82 ± 0.51 r.u.), glucose + isocitrate (2.71 ± 0.33 r.u.), glucose + malate (2.75 ± 0.38 r.u.), glucose + monomethyl-succinate (2.64 ± 0.42 r.u.) or glucose + dimethyl-α-ketoglutarate (2.36 ± 0.33 r.u.) comparing to glucose alone (1.73–2.02 r.u.) or no substrate (1.76 ± 0.33 r.u.). The optimal FCCP concentration was the highest (1.75 μM) upon glucose + glutamine + pyruvate combination and the lowest (0.5 μM) upon glutamate, combinations of glucose with isocitrate, malate, succinate or α-ketoglutarate. Respiration acceleration after FCCP application was the highest with dimethyl-α-ketoglutarate. Following the peak respiration, time-dependent deceleration was observed. It increased with FCCP concentration and depended on oxidative substrate type. Deceleration was the highest upon malate or isocitrate oxidation but was not observed in case of glutamine or dimethyl-α-ketoglutarate oxidation. Pyruvate alone or in combination with glutamine and glucose significantly decreased the depolarizing effect of FCCP on mitochondrial membrane potential and increased respiration elasticity coefficient with respect to the membrane potential change. Thus, in pancreatic acinar cells, the combination of pyruvate, glutamine and glucose enables the optimal adaptive respiratory response to membrane depolarization.http://ukrbiochemjournal.org/wp-content/uploads/2019/05/Manko_3_19.pdfdepolarizationmitochondriaoxidative substratesoxygen consumptionpancreatic acinusrespiratory uncouplers |
| spellingShingle | B. O. Manko O. O. Bilonoha V. V. Manko Adaptive respiratory response of rat pancreatic acinar cells to mitochondrial membrane depolarization The Ukrainian Biochemical Journal depolarization mitochondria oxidative substrates oxygen consumption pancreatic acinus respiratory uncouplers |
| title | Adaptive respiratory response of rat pancreatic acinar cells to mitochondrial membrane depolarization |
| title_full | Adaptive respiratory response of rat pancreatic acinar cells to mitochondrial membrane depolarization |
| title_fullStr | Adaptive respiratory response of rat pancreatic acinar cells to mitochondrial membrane depolarization |
| title_full_unstemmed | Adaptive respiratory response of rat pancreatic acinar cells to mitochondrial membrane depolarization |
| title_short | Adaptive respiratory response of rat pancreatic acinar cells to mitochondrial membrane depolarization |
| title_sort | adaptive respiratory response of rat pancreatic acinar cells to mitochondrial membrane depolarization |
| topic | depolarization mitochondria oxidative substrates oxygen consumption pancreatic acinus respiratory uncouplers |
| url | http://ukrbiochemjournal.org/wp-content/uploads/2019/05/Manko_3_19.pdf |
| work_keys_str_mv | AT bomanko adaptiverespiratoryresponseofratpancreaticacinarcellstomitochondrialmembranedepolarization AT oobilonoha adaptiverespiratoryresponseofratpancreaticacinarcellstomitochondrialmembranedepolarization AT vvmanko adaptiverespiratoryresponseofratpancreaticacinarcellstomitochondrialmembranedepolarization |