Dual hydrolytic role for Pb(II) ions

Microarray Analysis of Differential Gene Expression in Lead-Exposed Astrocytes

“…Studies five decades ago first reported the cleavage of ribonucleic acids by lead (Dimroth et al, 1950;Farkas, 1968). Since then, lead has been routinely used as a tool for the study of the secondary structure of tRNA (Krebs et al, 1972;Farkas et al, 1972;Pan et al, 1994;Otzen et al, 1994;Ciesiolka et al, 1998;Perreau et al, 1999), mRNA (Farkas, 1975), and rRNA molecules (Winter et al, 1997). Lead is capable of cleaving RNA at specific sites through a mechanism of nucleophilic attack (Brown et al, 1983).…”

“…Lead-induced RNA cleavage can occur both in vitro and in vivo (Kennedy et al, 1983). Under physiological conditions (pH 7.4 and 37°C) lead is 28 times more potent than the next most effective divalent cation, zinc, in cleaving RNA (Farkas, 1968;Otzen et al, 1994). Kennedy et al (1983) prepared postmitochondrial fractions from the brains of rat pups treated with 4% lead carbonate maternal milk for 2 days.…”

Microarray Analysis of Differential Gene Expression in Lead-Exposed Astrocytes

“…Studies five decades ago first reported the cleavage of ribonucleic acids by lead (Dimroth et al, 1950;Farkas, 1968). Since then, lead has been routinely used as a tool for the study of the secondary structure of tRNA (Krebs et al, 1972;Farkas et al, 1972;Pan et al, 1994;Otzen et al, 1994;Ciesiolka et al, 1998;Perreau et al, 1999), mRNA (Farkas, 1975), and rRNA molecules (Winter et al, 1997). Lead is capable of cleaving RNA at specific sites through a mechanism of nucleophilic attack (Brown et al, 1983).…”

“…Lead-induced RNA cleavage can occur both in vitro and in vivo (Kennedy et al, 1983). Under physiological conditions (pH 7.4 and 37°C) lead is 28 times more potent than the next most effective divalent cation, zinc, in cleaving RNA (Farkas, 1968;Otzen et al, 1994). Kennedy et al (1983) prepared postmitochondrial fractions from the brains of rat pups treated with 4% lead carbonate maternal milk for 2 days.…”

Lone Pair Functionality in Divalent Lead Compounds

“…It appears that in this oxidation state lead binds preferentially to thiol and phosphate groups in nucleic acids, proteins, and cell membranes. − Polarographic and circular dichroism studies have indicated that Pb(II) has an overall stabilizing effect when it interacts with double-helical DNA . By contrast, interactions of Pb(II) with RNA under biological conditions result in hydrolysis of the nucleic acid (with strand breakage), as in the case of yeast phenylalanine t RNA, , in which cleavage by millimolar concentrations of Pb(II) occurs mainly in the D-loop. − Pb(II) depolymerizes RNA faster than any other metal ion, and, because RNA but not DNA is degraded in this way, the 2‘-hydroxyl group is apparently involved in the reaction; it is presumed that a cyclic phosphate intermediate is formed when the 2‘-hydroxyl group attacks the phosphorus atom. As a result, the phosphodiester P−O bond is broken …”

“…7 By contrast, interactions of Pb(II) with RNA under biological conditions result in hydrolysis of the nucleic acid (with strand breakage), as in the case of yeast phenylalanine tRNA, 8,9 in which cleavage by millimolar concentrations of Pb-(II) occurs mainly in the D-loop. [10][11][12][13] Pb(II) depolymerizes RNA faster than any other metal ion, 14 and, because RNA but not DNA is degraded in this way, the 2′-hydroxyl group is apparently involved in the reaction; it is presumed that a cyclic phosphate intermediate is formed when the 2′-hydroxyl group attacks the phosphorus atom. As a result, the phosphodiester P-O bond is broken.…”

Moderating the Acidity of Pb(II)–Water Complexes through the Coordination of Nonaqueous Ligands: A Computational Study

“…One of the main observations that can partly explain the high biological toxicity of Pb­(II) is its ability to bind in many irregular coordination geometries with variable numbers of ligands. It also often affects the homeostasis of trace metal ions with smaller ionic radii, such as Ca 2+ , Zn 2+ , or Cu 2+ . − A well-documented example of lead’s biochemical activity is the catalytically induced rapid degradation of tRNA when it is bound to the two nucleobases, uracil and cytosine, and at least one water molecule. − …”

Microarray Analysis of Differential Gene Expression in Lead-Exposed Astrocytes

“…Studies five decades ago first reported the cleavage of ribonucleic acids by lead (Dimroth et al, 1950;Farkas, 1968). Since then, lead has been routinely used as a tool for the study of the secondary structure of tRNA (Krebs et al, 1972;Farkas et al, 1972;Pan et al, 1994;Otzen et al, 1994;Ciesiolka et al, 1998;Perreau et al, 1999), mRNA (Farkas, 1975), and rRNA molecules (Winter et al, 1997). Lead is capable of cleaving RNA at specific sites through a mechanism of nucleophilic attack (Brown et al, 1983).…”

“…Lead-induced RNA cleavage can occur both in vitro and in vivo (Kennedy et al, 1983). Under physiological conditions (pH 7.4 and 37°C) lead is 28 times more potent than the next most effective divalent cation, zinc, in cleaving RNA (Farkas, 1968;Otzen et al, 1994). Kennedy et al (1983) prepared postmitochondrial fractions from the brains of rat pups treated with 4% lead carbonate maternal milk for 2 days.…”

Lone Pair Functionality in Divalent Lead Compounds

“…It appears that in this oxidation state lead binds preferentially to thiol and phosphate groups in nucleic acids, proteins, and cell membranes. − Polarographic and circular dichroism studies have indicated that Pb(II) has an overall stabilizing effect when it interacts with double-helical DNA . By contrast, interactions of Pb(II) with RNA under biological conditions result in hydrolysis of the nucleic acid (with strand breakage), as in the case of yeast phenylalanine t RNA, , in which cleavage by millimolar concentrations of Pb(II) occurs mainly in the D-loop. − Pb(II) depolymerizes RNA faster than any other metal ion, and, because RNA but not DNA is degraded in this way, the 2‘-hydroxyl group is apparently involved in the reaction; it is presumed that a cyclic phosphate intermediate is formed when the 2‘-hydroxyl group attacks the phosphorus atom. As a result, the phosphodiester P−O bond is broken …”

“…7 By contrast, interactions of Pb(II) with RNA under biological conditions result in hydrolysis of the nucleic acid (with strand breakage), as in the case of yeast phenylalanine tRNA, 8,9 in which cleavage by millimolar concentrations of Pb-(II) occurs mainly in the D-loop. [10][11][12][13] Pb(II) depolymerizes RNA faster than any other metal ion, 14 and, because RNA but not DNA is degraded in this way, the 2′-hydroxyl group is apparently involved in the reaction; it is presumed that a cyclic phosphate intermediate is formed when the 2′-hydroxyl group attacks the phosphorus atom. As a result, the phosphodiester P-O bond is broken.…”

Moderating the Acidity of Pb(II)–Water Complexes through the Coordination of Nonaqueous Ligands: A Computational Study

“…One of the main observations that can partly explain the high biological toxicity of Pb­(II) is its ability to bind in many irregular coordination geometries with variable numbers of ligands. It also often affects the homeostasis of trace metal ions with smaller ionic radii, such as Ca 2+ , Zn 2+ , or Cu 2+ . − A well-documented example of lead’s biochemical activity is the catalytically induced rapid degradation of tRNA when it is bound to the two nucleobases, uracil and cytosine, and at least one water molecule. − …”

Microarray Analysis of Differential Gene Expression in Lead-Exposed Astrocytes

“…Studies five decades ago first reported the cleavage of ribonucleic acids by lead (Dimroth et al, 1950;Farkas, 1968). Since then, lead has been routinely used as a tool for the study of the secondary structure of tRNA (Krebs et al, 1972;Farkas et al, 1972;Pan et al, 1994;Otzen et al, 1994;Ciesiolka et al, 1998;Perreau et al, 1999), mRNA (Farkas, 1975), and rRNA molecules (Winter et al, 1997). Lead is capable of cleaving RNA at specific sites through a mechanism of nucleophilic attack (Brown et al, 1983).…”

“…Lead-induced RNA cleavage can occur both in vitro and in vivo (Kennedy et al, 1983). Under physiological conditions (pH 7.4 and 37°C) lead is 28 times more potent than the next most effective divalent cation, zinc, in cleaving RNA (Farkas, 1968;Otzen et al, 1994). Kennedy et al (1983) prepared postmitochondrial fractions from the brains of rat pups treated with 4% lead carbonate maternal milk for 2 days.…”

Lone Pair Functionality in Divalent Lead Compounds

“…It appears that in this oxidation state lead binds preferentially to thiol and phosphate groups in nucleic acids, proteins, and cell membranes. − Polarographic and circular dichroism studies have indicated that Pb(II) has an overall stabilizing effect when it interacts with double-helical DNA . By contrast, interactions of Pb(II) with RNA under biological conditions result in hydrolysis of the nucleic acid (with strand breakage), as in the case of yeast phenylalanine t RNA, , in which cleavage by millimolar concentrations of Pb(II) occurs mainly in the D-loop. − Pb(II) depolymerizes RNA faster than any other metal ion, and, because RNA but not DNA is degraded in this way, the 2‘-hydroxyl group is apparently involved in the reaction; it is presumed that a cyclic phosphate intermediate is formed when the 2‘-hydroxyl group attacks the phosphorus atom. As a result, the phosphodiester P−O bond is broken …”

“…7 By contrast, interactions of Pb(II) with RNA under biological conditions result in hydrolysis of the nucleic acid (with strand breakage), as in the case of yeast phenylalanine tRNA, 8,9 in which cleavage by millimolar concentrations of Pb-(II) occurs mainly in the D-loop. [10][11][12][13] Pb(II) depolymerizes RNA faster than any other metal ion, 14 and, because RNA but not DNA is degraded in this way, the 2′-hydroxyl group is apparently involved in the reaction; it is presumed that a cyclic phosphate intermediate is formed when the 2′-hydroxyl group attacks the phosphorus atom. As a result, the phosphodiester P-O bond is broken.…”

Moderating the Acidity of Pb(II)–Water Complexes through the Coordination of Nonaqueous Ligands: A Computational Study

“…One of the main observations that can partly explain the high biological toxicity of Pb­(II) is its ability to bind in many irregular coordination geometries with variable numbers of ligands. It also often affects the homeostasis of trace metal ions with smaller ionic radii, such as Ca 2+ , Zn 2+ , or Cu 2+ . − A well-documented example of lead’s biochemical activity is the catalytically induced rapid degradation of tRNA when it is bound to the two nucleobases, uracil and cytosine, and at least one water molecule. − …”