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Achieving excellence in the fields of education, scientific research, and community service, and promote the university to the level the prestigious universities locally, regionally and globally.
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Prof. Jalal Aljamal Doctorate / Full Professor
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Research Interests:
Ion Channel Receptors:
The broad objective of my research is to understand the molecular mechanism underlying the voltage control of membrane channels. I focused on the macromolecules, mainly proteins that are lodged within cell membranes and translocate molecules and ions across the membranes. Channel-forming proteins that are under voltage control are responsible for processes such as action potentials, muscle excitation, hormone release. The channel-former being studied is called VDAC. It is located in the mitochondrial outer membrane and may control most of the energy production in animal cells.
The research is highly interdisciplinary and includes isolating and purifying cell organelles, purifying soluble and membrane proteins, reconstituting proteins into vesicles and planar phospholipid membranes, making electrophysiological recordings on individual channel-forming molecules as well as ensembles of molecules, and studies of chemically-modified channels.
Current work deals with:
1- The effect of fetal and neonatal hypothyroidism on the developmental changes in the amount of the hexokinase binding protein as a marker of mitochondrial differentiation.
2- Role of voltage dependent anion selective channel in various forms of mitochondrial changes in mammalian cells.
Awards Received:
The University of Philadelphia award for excellence in research, 2004 – 2005
Recent Research Publications 1- ANTIDIABETIC EFFECT OF ETHANOLIC EXTRACT OF TRAGANUM NUDATUM ON ALLOXAN INDUCED DIABETICS WISTAR RATS BADAWNEH, JALAL ALJAMAL, BANDAR, ALSEHLI IJBPAS Download × ANTIDIABETIC EFFECT OF ETHANOLIC EXTRACT OF TRAGANUM NUDATUM ON ALLOXAN INDUCED DIABETICS WISTAR RATS ABSTRACT Traganum nudatum (T. nudatum) is a medicinal plant widely used in folk medicine. In this study, we have undertaken the biological effects of T. nudatum ethanolic whole plant extracts in alloxan induced diabetic rats. Sixty albino rats (260 g) were used in this experiment and divided into six groups. Diabetes was induced in five rat groups by a single intraperitoneal injection of alloxan (150 mg/kg body weight). After hyperglycemia was confirmed, one group was considered as diabetic control and one group was treated with Glibenclamide (10 mg/kg body weight/ daily) where the remaining three groups received daily treatments with three different doses of T. nudatum extract (100, 200, and 400 mg/kg body weight) for 21 days each dissolved in 1 ml distilled water was administered intraperitoneally to each corresponding rat group. Blood serum biochemical markers such as urea, creatinine, cholesterol, and total serum protein levels were recorded after the treatment ended. Findings indicate that treatment with medium and high doses of T. nudatum extract (200 and 400 mg/kg/ body weight) reduces blood sugar values to significant levels (P<0.001) The study concluded that ethanolic extracts of T. nudatum treatment exhibits a significant antihyperglycemic effect without altering the body weight and can correct some biochemical markers induced by diabetes in a similar manner or better than to Glibenclamide in alloxaninduced diabetic wistar rats. BADAWNEH, JALAL ALJAMAL, BANDAR, ALSEHLI Journal: 2- Effect of Lysine and Histidine Residues Modification on the Voltage Gating of the Mitochondrial Porin Jalal Aljamal Journal of Biochemical Technology Download × Effect of Lysine and Histidine Residues Modification on the Voltage Gating of the Mitochondrial Porin Abstract Mitochondrial porin is a complex channel with many diverse functional properties. Therefore, along with measuring singlechannel conductance and selectivity, monitoring VDAC's voltage gating has become the gold standard for assessing mitochondrial porin function. To understand the mechanisms of gating and ion selectivity, the detergent-solubilized porin was incubated with different concentrations of diethylpyrocarbonate (DEPC). The extent of the reaction of DEPC with histidine residues was monitored by differential absorbance at 242 nm. The resulting modified proteins were loaded onto (CM-cellulose) columns, and the collected fractions were examined for their activity. The apparent ion selectivity was determined by measuring the membrane potential at zero-current conditions. The reversal potentials obtained for the unmodified-porin and ethoxyformylporin eluted from the resin (CMC-52) with the equilibration buffer were, respectively, +7 mV and -6 mV. The activity was slowly restored by incubation with hydroxylamine, and the extent of reversal depended on the reagent's concentration. The histidine residues are non-essential in the voltage-gating process since their modification has no direct impact on porin inactivation. However, the decrease of both the channel conductance and the critical potential needed to close the channel resulted from the covalent modification of one or more lysine residues in the EF-porin fraction, suggesting that lysine residues may contribute, in a unique way, to the gating process. Jalal Aljamal Journal: 3- In vitro inhibition of human erythrocyte hexokinase by various hyperglycemic drugs Jalal A. Aljamal, Muwaffag Badawneh Journal of biochemical and molecular toxicology Download × In vitro inhibition of human erythrocyte hexokinase by various hyperglycemic drugs Hemolysis is the red blood cell abnormality most often associated with adverse effect of drug therapy. Drug-induced or drug-associated hyperglycemia could decrease the activity of hexokinase. The aim of this study was to investigate the inhibitory effects of some commonly used drugs that have hyperglycemic side effect on the human erythrocyte hexokinase enzyme in vitro. Hexokinase was purified from human erythrocytes using sequential chromatography, with a specific activity of 0.96 ± 0.18 U/g hemoglobin, and assayed in the presence of selected drugs that have hyperglycemic side effect. The IC50 were determined from the regression analysis graph. Correlation analysis showed that there was positive correlation between the hyperglycemic side effect of some of the tested drugs and decrease of hexokinase activity. This suggests that, at least in part, these drugs exert their hyperglycemic effect by inhibiting glucose phosphorylation by the hexokinase, which consequently causes the glucose accumulation. Jalal A. Aljamal, Muwaffag Badawneh Journal: 4- Antilipolytic effects of 1, 8‐naphthyridine derivatives β‐adrenoceptor antagonists in rat white adipocytes Jalal A Aljamal, Muwaffag Badawneh Chemical biology & drug design Download × Antilipolytic effects of 1, 8‐naphthyridine derivatives β‐adrenoceptor antagonists in rat white adipocytes The rat fat cell β-adrenoceptors were investigated by studying the effects of new 1,8-naphthyridine derivatives synthesized starting from 7-amino-2-chloro-3-phenyl-1,8-naphthyridine on lipolysis induced by isoprenaline, and alprenolol. Lipolysis induced by isoprenaline agonist was competitively antagonized by the 1,8-naphthyridine analogue with a 7-hydroxy-2-(4′-methoxybenzylamine)-6-nitro-3-phenyl substituent designated as 3. In contrast, 10, 50, and 100 μm of 7-methoxy and 7-ethoxy derivatives did not modify the concentration–response curve of isoprenaline. A rightward shift of the curve was, however, observed with 50 μm of a 7-methoxy-2-(4′-methoxybenzylamine)-6-amino-3-phenyl substituent designated as 10. The selective β1-AR antagonist, 7-hydroxy-4-morpholinomethyl-2-piperazino-1,8-naphthyridine slightly reduced isoprenaline-induced lipolysis only at high doses. Alprenolol-mediated lipolytic effect was antagonized by derivative 3, 10 and the selective β3-AR antagonist SR 59,230A, but resistant to the selective β1-AR antagonist 7-hydroxy-4-morpholinomethyl-2-piperazino-1,8-naphthyridine. The results provide preliminary pharmacological evidence for the antilipolytic effect of the newly synthesized 1,8-naphthyridine derivatives on rat fat cells. The analogues designated as 3 and 10 were the most potent antagonists of this series Jalal A Aljamal, Muwaffag Badawneh Journal: 5- Effect of different thyroid states on mitochondrial porin synthesis and hexokinase activity in developing rabbit brain Jalal A. Aljamal Journal of biochemistry Download × Effect of different thyroid states on mitochondrial porin synthesis and hexokinase activity in developing rabbit brain Voltage-dependent anion-selective channel proteins (VDACs) are pore-forming proteins found in the outer mitochondrial membrane of all eukaryotes and in brain postsynaptic membranes. VDACs regulate anion fluxes of a series of metabolites including ATP, thus regulating mitochondrial metabolic functions. Hexokinase binds to porin. The mitochondrially bound hexokinase can greatly increase the rate of aerobic glycolysis. The activities of hexokinase and protein levels of mitochondrial porin were determined in brains of hypothyroid rabbits and in hypothyroid rabbits administered with thyroxine. Proteins were separated by electrophoresis, and the proteins of interest were quantified. Western blotting analysis revealed a significant decrease (~50%) in the relative amount of porin in the hypothyroid compared with euthyroid rabbits. The changes in the developmental pattern of hexokinase activity in the brain of hypothyroid rabbits and the effect of T4 on this enzyme activity have been investigated. Hypothyroid rabbits showed lower activity than their corresponding age-matched normal neonates. Administration of thyroxine to the hypothyroid neonates at birth abolished the effects of methimazole [1-methyl-2-mercaptoimidazole (MMI)]. These findings apparently indicate that the synthesis of the pore-forming protein and the hexokinase enzymes are under thyroid control during the fetal and the early postnatal period. Jalal A. Aljamal Journal:
ABSTRACT Traganum nudatum (T. nudatum) is a medicinal plant widely used in folk medicine. In this study, we have undertaken the biological effects of T. nudatum ethanolic whole plant extracts in alloxan induced diabetic rats. Sixty albino rats (260 g) were used in this experiment and divided into six groups. Diabetes was induced in five rat groups by a single intraperitoneal injection of alloxan (150 mg/kg body weight). After hyperglycemia was confirmed, one group was considered as diabetic control and one group was treated with Glibenclamide (10 mg/kg body weight/ daily) where the remaining three groups received daily treatments with three different doses of T. nudatum extract (100, 200, and 400 mg/kg body weight) for 21 days each dissolved in 1 ml distilled water was administered intraperitoneally to each corresponding rat group. Blood serum biochemical markers such as urea, creatinine, cholesterol, and total serum protein levels were recorded after the treatment ended. Findings indicate that treatment with medium and high doses of T. nudatum extract (200 and 400 mg/kg/ body weight) reduces blood sugar values to significant levels (P<0.001) The study concluded that ethanolic extracts of T. nudatum treatment exhibits a significant antihyperglycemic effect without altering the body weight and can correct some biochemical markers induced by diabetes in a similar manner or better than to Glibenclamide in alloxaninduced diabetic wistar rats.
Abstract Mitochondrial porin is a complex channel with many diverse functional properties. Therefore, along with measuring singlechannel conductance and selectivity, monitoring VDAC's voltage gating has become the gold standard for assessing mitochondrial porin function. To understand the mechanisms of gating and ion selectivity, the detergent-solubilized porin was incubated with different concentrations of diethylpyrocarbonate (DEPC). The extent of the reaction of DEPC with histidine residues was monitored by differential absorbance at 242 nm. The resulting modified proteins were loaded onto (CM-cellulose) columns, and the collected fractions were examined for their activity. The apparent ion selectivity was determined by measuring the membrane potential at zero-current conditions. The reversal potentials obtained for the unmodified-porin and ethoxyformylporin eluted from the resin (CMC-52) with the equilibration buffer were, respectively, +7 mV and -6 mV. The activity was slowly restored by incubation with hydroxylamine, and the extent of reversal depended on the reagent's concentration. The histidine residues are non-essential in the voltage-gating process since their modification has no direct impact on porin inactivation. However, the decrease of both the channel conductance and the critical potential needed to close the channel resulted from the covalent modification of one or more lysine residues in the EF-porin fraction, suggesting that lysine residues may contribute, in a unique way, to the gating process.
Hemolysis is the red blood cell abnormality most often associated with adverse effect of drug therapy. Drug-induced or drug-associated hyperglycemia could decrease the activity of hexokinase. The aim of this study was to investigate the inhibitory effects of some commonly used drugs that have hyperglycemic side effect on the human erythrocyte hexokinase enzyme in vitro. Hexokinase was purified from human erythrocytes using sequential chromatography, with a specific activity of 0.96 ± 0.18 U/g hemoglobin, and assayed in the presence of selected drugs that have hyperglycemic side effect. The IC50 were determined from the regression analysis graph. Correlation analysis showed that there was positive correlation between the hyperglycemic side effect of some of the tested drugs and decrease of hexokinase activity. This suggests that, at least in part, these drugs exert their hyperglycemic effect by inhibiting glucose phosphorylation by the hexokinase, which consequently causes the glucose accumulation.
The rat fat cell β-adrenoceptors were investigated by studying the effects of new 1,8-naphthyridine derivatives synthesized starting from 7-amino-2-chloro-3-phenyl-1,8-naphthyridine on lipolysis induced by isoprenaline, and alprenolol. Lipolysis induced by isoprenaline agonist was competitively antagonized by the 1,8-naphthyridine analogue with a 7-hydroxy-2-(4′-methoxybenzylamine)-6-nitro-3-phenyl substituent designated as 3. In contrast, 10, 50, and 100 μm of 7-methoxy and 7-ethoxy derivatives did not modify the concentration–response curve of isoprenaline. A rightward shift of the curve was, however, observed with 50 μm of a 7-methoxy-2-(4′-methoxybenzylamine)-6-amino-3-phenyl substituent designated as 10. The selective β1-AR antagonist, 7-hydroxy-4-morpholinomethyl-2-piperazino-1,8-naphthyridine slightly reduced isoprenaline-induced lipolysis only at high doses. Alprenolol-mediated lipolytic effect was antagonized by derivative 3, 10 and the selective β3-AR antagonist SR 59,230A, but resistant to the selective β1-AR antagonist 7-hydroxy-4-morpholinomethyl-2-piperazino-1,8-naphthyridine. The results provide preliminary pharmacological evidence for the antilipolytic effect of the newly synthesized 1,8-naphthyridine derivatives on rat fat cells. The analogues designated as 3 and 10 were the most potent antagonists of this series
Voltage-dependent anion-selective channel proteins (VDACs) are pore-forming proteins found in the outer mitochondrial membrane of all eukaryotes and in brain postsynaptic membranes. VDACs regulate anion fluxes of a series of metabolites including ATP, thus regulating mitochondrial metabolic functions. Hexokinase binds to porin. The mitochondrially bound hexokinase can greatly increase the rate of aerobic glycolysis. The activities of hexokinase and protein levels of mitochondrial porin were determined in brains of hypothyroid rabbits and in hypothyroid rabbits administered with thyroxine. Proteins were separated by electrophoresis, and the proteins of interest were quantified. Western blotting analysis revealed a significant decrease (~50%) in the relative amount of porin in the hypothyroid compared with euthyroid rabbits. The changes in the developmental pattern of hexokinase activity in the brain of hypothyroid rabbits and the effect of T4 on this enzyme activity have been investigated. Hypothyroid rabbits showed lower activity than their corresponding age-matched normal neonates. Administration of thyroxine to the hypothyroid neonates at birth abolished the effects of methimazole [1-methyl-2-mercaptoimidazole (MMI)]. These findings apparently indicate that the synthesis of the pore-forming protein and the hexokinase enzymes are under thyroid control during the fetal and the early postnatal period.
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