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Brenner M Fissell - One of the best experts on this subject based on the ideXlab platform.
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capital punishment of unintentional felony murder
Notre Dame Law Review, 2017Co-Authors: Guyora Binder, Brenner M Fissell, Robert WeisbergAbstract:Under the prevailing interpretation of the Eighth Amendment in the lower courts, a defendant who causes a death inadvertently in the course of a felony is eligible for capital punishment. This unfortunate interpretation rests on an unduly mechanical reading of the Supreme Court's decisions in Enmund v. Florida and Tison v. Arizona, which require culpability for capital punishment of co-felons who do not kill. The lower courts have drawn the unwarranted inference that these cases permit execution of those who cause death without any culpability towards death. This Article shows that this mechanical reading of precedent is mistaken, because the underlying justifications of Eighth Amendment jurisprudence require a rational selection for death of only the most deserving and deferrable offenders, and this in turn requires an assessment of culpability. We argue that the Supreme Court should address this open question in Eighth Amendment law and that it should correct the lower courts by imposing a Uniform Requirement of at least recklessness with respect to death for capital punishment of felony murder. INTRODUCTION That a defendant could be executed for causing death inadvertently might seem absurd. Nevertheless, the great majority of American courts to have considered the question have concluded that the Eighth Amendment of the U.S. Constitution permits such executions. In so doing, they have interpreted Supreme Court doctrine to allow capital punishment of any person who causes death during the commission of a felony, regardless of that person's mental state with respect to the resultant death. Under this reading of precedent, the following defendants are eligible for the death penalty: the driver of a getaway car who kills a jaywalker, the burglar who starles an elderly homeowner and causes a fatal heart attack, and the robber who unknowingly punches a hemophiliac. Such counterintuitive results become conceivable when eligibility for the death penalty is untethered from the defendant's culpability. This disconnect results from an overly mechanical interpretation of the Supreme Court's two key cases applying the Eighth Amendment to the felony murder context: Enmund v. Florida (1) and Tison v. Arizona. (2) Although these cases have been read to permit execution of nonculpable killers, the holdings of both decisions impose a high level of culpability for execution of accomplices in felony murder, on the ground that death should be reserved for the most culpable offenders. In overturning the death sentence of an accomplice in a fatal felony, the Enmund majority stated that a participant in a fatal felony is ineligible for capital punishment if he "does not himself kill, attempt to kill, or intend that a killing take place or that lethal force will be employed." (3) In upholding the death sentences of two accomplices in a fatal felony, the Tison majority permitted capital punishment of felons "whose participation is major and whose mental state is one of reckless indifference to the value of human life." (4) Thus, subsequent readings of Enmund and Tison that permit the execution of actual killers regardless of culpability are largely based on what they did not say about a question that was not before them. To be sure, the Enmund majority did not say that those who "kill" are eligible only if they intend death, but neither did it say they are eligible regardless of their mental state. The Tison majority concluded that Enmund "held" that capital punishment could be imposed on "the felony murderer who actually killed," (5) but only "when the circumstances warranted." (6) Because both cases concerned accomplices of intentional killers, neither Court specified whether those who "killed" included all who caused death, by any means, and with any mental state. Yet most lower courts have assumed that anyone causing death in a predicate felony is death-eligible, regardless of any culpability. Omitting consideration of a culpable mental state is at odds with a central background principle of Eighth Amendment law: that we may only execute people to advance deterrence and retribution and that neither can be furthered if the person does not act with culpability. …
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capital punishment of unintentional felony murder
Social Science Research Network, 2017Co-Authors: Guyora Binder, Robert Weisberg, Brenner M FissellAbstract:Under the prevailing interpretation of the Eighth Amendment in the lower courts, a defendant who causes a death inadvertently in the course of a felony is eligible for capital punishment. This unfortunate interpretation rests on an unduly mechanical reading of the Supreme Court’s decisions in Enmund v. Florida and Tison v. Arizona, which require culpability for capital punishment of co-felons who do not kill. The lower courts have drawn the unwarranted inference that these cases permit execution of those who cause death without any culpability towards death. This Article shows that this mechanical reading of precedent is mistaken, because the underlying justifications of Eighth Amendment jurisprudence require a rational selection for death of only the most deserving and deterrable offenders, and this in turn requires an assessment of culpability. We argue that the Supreme Court should address this open question in Eighth Amendment law and that it should correct the lower courts by imposing a Uniform Requirement of at least recklessness with respect to death for capital punishment of felony murder.
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capital punishment of unintentional felony murder
Notre Dame Law Review, 2017Co-Authors: Guyora Binder, Brenner M Fissell, Robert WeisbergAbstract:Under the prevailing interpretation of the Eighth Amendment in the lower courts, a defendant who causes a death inadvertently in the course of a felony is eligible for capital punishment. This unfortunate interpretation rests on an unduly mechanical reading of the Supreme Court's decisions in Enmund v. Florida and Tison v. Arizona, which require culpability for capital punishment of co-felons who do not kill. The lower courts have drawn the unwarranted inference that these cases permit execution of those who cause death without any culpability towards death. This Article shows that this mechanical reading of precedent is mistaken, because the underlying justifications of Eighth Amendment jurisprudence require a rational selection for death of only the most deserving and deferrable offenders, and this in turn requires an assessment of culpability. We argue that the Supreme Court should address this open question in Eighth Amendment law and that it should correct the lower courts by imposing a Uniform Requirement of at least recklessness with respect to death for capital punishment of felony murder. INTRODUCTION That a defendant could be executed for causing death inadvertently might seem absurd. Nevertheless, the great majority of American courts to have considered the question have concluded that the Eighth Amendment of the U.S. Constitution permits such executions. In so doing, they have interpreted Supreme Court doctrine to allow capital punishment of any person who causes death during the commission of a felony, regardless of that person's mental state with respect to the resultant death. Under this reading of precedent, the following defendants are eligible for the death penalty: the driver of a getaway car who kills a jaywalker, the burglar who starles an elderly homeowner and causes a fatal heart attack, and the robber who unknowingly punches a hemophiliac. Such counterintuitive results become conceivable when eligibility for the death penalty is untethered from the defendant's culpability. This disconnect results from an overly mechanical interpretation of the Supreme Court's two key cases applying the Eighth Amendment to the felony murder context: Enmund v. Florida (1) and Tison v. Arizona. (2) Although these cases have been read to permit execution of nonculpable killers, the holdings of both decisions impose a high level of culpability for execution of accomplices in felony murder, on the ground that death should be reserved for the most culpable offenders. In overturning the death sentence of an accomplice in a fatal felony, the Enmund majority stated that a participant in a fatal felony is ineligible for capital punishment if he "does not himself kill, attempt to kill, or intend that a killing take place or that lethal force will be employed." (3) In upholding the death sentences of two accomplices in a fatal felony, the Tison majority permitted capital punishment of felons "whose participation is major and whose mental state is one of reckless indifference to the value of human life." (4) Thus, subsequent readings of Enmund and Tison that permit the execution of actual killers regardless of culpability are largely based on what they did not say about a question that was not before them. To be sure, the Enmund majority did not say that those who "kill" are eligible only if they intend death, but neither did it say they are eligible regardless of their mental state. The Tison majority concluded that Enmund "held" that capital punishment could be imposed on "the felony murderer who actually killed," (5) but only "when the circumstances warranted." (6) Because both cases concerned accomplices of intentional killers, neither Court specified whether those who "killed" included all who caused death, by any means, and with any mental state. Yet most lower courts have assumed that anyone causing death in a predicate felony is death-eligible, regardless of any culpability. Omitting consideration of a culpable mental state is at odds with a central background principle of Eighth Amendment law: that we may only execute people to advance deterrence and retribution and that neither can be furthered if the person does not act with culpability. …
Jane M Bryson - One of the best experts on this subject based on the ideXlab platform.
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regulation of mesangial cell hexokinase activity and expression by heparin binding epidermal growth factor like growth factor epidermal growth factors and phorbol esters increase glucose metabolism via a common mechanism involving classic mitogen activated protein kinase pathway activation and induction of hexokinase ii expression
Journal of Biological Chemistry, 2002Co-Authors: Brooks R Robey, Anna V P Santos, Oscar Noboa, Jane M BrysonAbstract:Heparin-binding epidermal growth factor -like growth factor (HB-EGF) expression and hexokinase (HK) activity are increased in various pathologic renal conditions. Although the mitogenic properties of HB-EGF have been well characterized, its effects on glucose (Glc) metabolism have not. We therefore examined the possibility that HB-EGF might regulate HK activity and expression in glomerular mesangial cells, which constitute the principal renal cell type affected by a variety of pathologic conditions. Protein kinase C (PKC)-dependent classic mitogen-activated protein kinase (MAPK) pathway activation has been associated with increased HK activity in this cell type, so we also examined dependence upon these signaling intermediates. HB-EGF (> or =10 nm) increased total HK activity over 50% within 12-24 h, an effect mimicked by other EGF receptor agonists, but not by IGF-1 or elevated Glc. EGF receptor and classic MAPK pathway antagonists prevented this increase, as did general inhibitors of gene transcription and protein synthesis. Both HB-EGF and phorbol esters activated the classic MAPK pathway, albeit via PKC-independent and PKC-dependent mechanisms, respectively. Both stimuli were associated with increased HK activity, selectively increased HKII isoform expression, and increased Glc metabolism via both the glycolytic-tricarboxylic acid cycle route and the pentose phosphate pathway. HB-EGF thus constitutes a novel regulator of mesangial cell HK activity and Glc metabolism. HKII is the principal regulated isoform in these cells, as it is in insulin-sensitive peripheral tissues, such as muscle. However, the Uniform Requirement for classic MAPK pathway activation distinguishes HKII regulation in mesangial cells from that observed in muscle. These findings suggest a novel mechanism whereby growth factors may couple metabolism to glomerular injury.
Guyora Binder - One of the best experts on this subject based on the ideXlab platform.
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capital punishment of unintentional felony murder
Notre Dame Law Review, 2017Co-Authors: Guyora Binder, Brenner M Fissell, Robert WeisbergAbstract:Under the prevailing interpretation of the Eighth Amendment in the lower courts, a defendant who causes a death inadvertently in the course of a felony is eligible for capital punishment. This unfortunate interpretation rests on an unduly mechanical reading of the Supreme Court's decisions in Enmund v. Florida and Tison v. Arizona, which require culpability for capital punishment of co-felons who do not kill. The lower courts have drawn the unwarranted inference that these cases permit execution of those who cause death without any culpability towards death. This Article shows that this mechanical reading of precedent is mistaken, because the underlying justifications of Eighth Amendment jurisprudence require a rational selection for death of only the most deserving and deferrable offenders, and this in turn requires an assessment of culpability. We argue that the Supreme Court should address this open question in Eighth Amendment law and that it should correct the lower courts by imposing a Uniform Requirement of at least recklessness with respect to death for capital punishment of felony murder. INTRODUCTION That a defendant could be executed for causing death inadvertently might seem absurd. Nevertheless, the great majority of American courts to have considered the question have concluded that the Eighth Amendment of the U.S. Constitution permits such executions. In so doing, they have interpreted Supreme Court doctrine to allow capital punishment of any person who causes death during the commission of a felony, regardless of that person's mental state with respect to the resultant death. Under this reading of precedent, the following defendants are eligible for the death penalty: the driver of a getaway car who kills a jaywalker, the burglar who starles an elderly homeowner and causes a fatal heart attack, and the robber who unknowingly punches a hemophiliac. Such counterintuitive results become conceivable when eligibility for the death penalty is untethered from the defendant's culpability. This disconnect results from an overly mechanical interpretation of the Supreme Court's two key cases applying the Eighth Amendment to the felony murder context: Enmund v. Florida (1) and Tison v. Arizona. (2) Although these cases have been read to permit execution of nonculpable killers, the holdings of both decisions impose a high level of culpability for execution of accomplices in felony murder, on the ground that death should be reserved for the most culpable offenders. In overturning the death sentence of an accomplice in a fatal felony, the Enmund majority stated that a participant in a fatal felony is ineligible for capital punishment if he "does not himself kill, attempt to kill, or intend that a killing take place or that lethal force will be employed." (3) In upholding the death sentences of two accomplices in a fatal felony, the Tison majority permitted capital punishment of felons "whose participation is major and whose mental state is one of reckless indifference to the value of human life." (4) Thus, subsequent readings of Enmund and Tison that permit the execution of actual killers regardless of culpability are largely based on what they did not say about a question that was not before them. To be sure, the Enmund majority did not say that those who "kill" are eligible only if they intend death, but neither did it say they are eligible regardless of their mental state. The Tison majority concluded that Enmund "held" that capital punishment could be imposed on "the felony murderer who actually killed," (5) but only "when the circumstances warranted." (6) Because both cases concerned accomplices of intentional killers, neither Court specified whether those who "killed" included all who caused death, by any means, and with any mental state. Yet most lower courts have assumed that anyone causing death in a predicate felony is death-eligible, regardless of any culpability. Omitting consideration of a culpable mental state is at odds with a central background principle of Eighth Amendment law: that we may only execute people to advance deterrence and retribution and that neither can be furthered if the person does not act with culpability. …
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capital punishment of unintentional felony murder
Social Science Research Network, 2017Co-Authors: Guyora Binder, Robert Weisberg, Brenner M FissellAbstract:Under the prevailing interpretation of the Eighth Amendment in the lower courts, a defendant who causes a death inadvertently in the course of a felony is eligible for capital punishment. This unfortunate interpretation rests on an unduly mechanical reading of the Supreme Court’s decisions in Enmund v. Florida and Tison v. Arizona, which require culpability for capital punishment of co-felons who do not kill. The lower courts have drawn the unwarranted inference that these cases permit execution of those who cause death without any culpability towards death. This Article shows that this mechanical reading of precedent is mistaken, because the underlying justifications of Eighth Amendment jurisprudence require a rational selection for death of only the most deserving and deterrable offenders, and this in turn requires an assessment of culpability. We argue that the Supreme Court should address this open question in Eighth Amendment law and that it should correct the lower courts by imposing a Uniform Requirement of at least recklessness with respect to death for capital punishment of felony murder.
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capital punishment of unintentional felony murder
Notre Dame Law Review, 2017Co-Authors: Guyora Binder, Brenner M Fissell, Robert WeisbergAbstract:Under the prevailing interpretation of the Eighth Amendment in the lower courts, a defendant who causes a death inadvertently in the course of a felony is eligible for capital punishment. This unfortunate interpretation rests on an unduly mechanical reading of the Supreme Court's decisions in Enmund v. Florida and Tison v. Arizona, which require culpability for capital punishment of co-felons who do not kill. The lower courts have drawn the unwarranted inference that these cases permit execution of those who cause death without any culpability towards death. This Article shows that this mechanical reading of precedent is mistaken, because the underlying justifications of Eighth Amendment jurisprudence require a rational selection for death of only the most deserving and deferrable offenders, and this in turn requires an assessment of culpability. We argue that the Supreme Court should address this open question in Eighth Amendment law and that it should correct the lower courts by imposing a Uniform Requirement of at least recklessness with respect to death for capital punishment of felony murder. INTRODUCTION That a defendant could be executed for causing death inadvertently might seem absurd. Nevertheless, the great majority of American courts to have considered the question have concluded that the Eighth Amendment of the U.S. Constitution permits such executions. In so doing, they have interpreted Supreme Court doctrine to allow capital punishment of any person who causes death during the commission of a felony, regardless of that person's mental state with respect to the resultant death. Under this reading of precedent, the following defendants are eligible for the death penalty: the driver of a getaway car who kills a jaywalker, the burglar who starles an elderly homeowner and causes a fatal heart attack, and the robber who unknowingly punches a hemophiliac. Such counterintuitive results become conceivable when eligibility for the death penalty is untethered from the defendant's culpability. This disconnect results from an overly mechanical interpretation of the Supreme Court's two key cases applying the Eighth Amendment to the felony murder context: Enmund v. Florida (1) and Tison v. Arizona. (2) Although these cases have been read to permit execution of nonculpable killers, the holdings of both decisions impose a high level of culpability for execution of accomplices in felony murder, on the ground that death should be reserved for the most culpable offenders. In overturning the death sentence of an accomplice in a fatal felony, the Enmund majority stated that a participant in a fatal felony is ineligible for capital punishment if he "does not himself kill, attempt to kill, or intend that a killing take place or that lethal force will be employed." (3) In upholding the death sentences of two accomplices in a fatal felony, the Tison majority permitted capital punishment of felons "whose participation is major and whose mental state is one of reckless indifference to the value of human life." (4) Thus, subsequent readings of Enmund and Tison that permit the execution of actual killers regardless of culpability are largely based on what they did not say about a question that was not before them. To be sure, the Enmund majority did not say that those who "kill" are eligible only if they intend death, but neither did it say they are eligible regardless of their mental state. The Tison majority concluded that Enmund "held" that capital punishment could be imposed on "the felony murderer who actually killed," (5) but only "when the circumstances warranted." (6) Because both cases concerned accomplices of intentional killers, neither Court specified whether those who "killed" included all who caused death, by any means, and with any mental state. Yet most lower courts have assumed that anyone causing death in a predicate felony is death-eligible, regardless of any culpability. Omitting consideration of a culpable mental state is at odds with a central background principle of Eighth Amendment law: that we may only execute people to advance deterrence and retribution and that neither can be furthered if the person does not act with culpability. …
Robert Weisberg - One of the best experts on this subject based on the ideXlab platform.
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capital punishment of unintentional felony murder
Notre Dame Law Review, 2017Co-Authors: Guyora Binder, Brenner M Fissell, Robert WeisbergAbstract:Under the prevailing interpretation of the Eighth Amendment in the lower courts, a defendant who causes a death inadvertently in the course of a felony is eligible for capital punishment. This unfortunate interpretation rests on an unduly mechanical reading of the Supreme Court's decisions in Enmund v. Florida and Tison v. Arizona, which require culpability for capital punishment of co-felons who do not kill. The lower courts have drawn the unwarranted inference that these cases permit execution of those who cause death without any culpability towards death. This Article shows that this mechanical reading of precedent is mistaken, because the underlying justifications of Eighth Amendment jurisprudence require a rational selection for death of only the most deserving and deferrable offenders, and this in turn requires an assessment of culpability. We argue that the Supreme Court should address this open question in Eighth Amendment law and that it should correct the lower courts by imposing a Uniform Requirement of at least recklessness with respect to death for capital punishment of felony murder. INTRODUCTION That a defendant could be executed for causing death inadvertently might seem absurd. Nevertheless, the great majority of American courts to have considered the question have concluded that the Eighth Amendment of the U.S. Constitution permits such executions. In so doing, they have interpreted Supreme Court doctrine to allow capital punishment of any person who causes death during the commission of a felony, regardless of that person's mental state with respect to the resultant death. Under this reading of precedent, the following defendants are eligible for the death penalty: the driver of a getaway car who kills a jaywalker, the burglar who starles an elderly homeowner and causes a fatal heart attack, and the robber who unknowingly punches a hemophiliac. Such counterintuitive results become conceivable when eligibility for the death penalty is untethered from the defendant's culpability. This disconnect results from an overly mechanical interpretation of the Supreme Court's two key cases applying the Eighth Amendment to the felony murder context: Enmund v. Florida (1) and Tison v. Arizona. (2) Although these cases have been read to permit execution of nonculpable killers, the holdings of both decisions impose a high level of culpability for execution of accomplices in felony murder, on the ground that death should be reserved for the most culpable offenders. In overturning the death sentence of an accomplice in a fatal felony, the Enmund majority stated that a participant in a fatal felony is ineligible for capital punishment if he "does not himself kill, attempt to kill, or intend that a killing take place or that lethal force will be employed." (3) In upholding the death sentences of two accomplices in a fatal felony, the Tison majority permitted capital punishment of felons "whose participation is major and whose mental state is one of reckless indifference to the value of human life." (4) Thus, subsequent readings of Enmund and Tison that permit the execution of actual killers regardless of culpability are largely based on what they did not say about a question that was not before them. To be sure, the Enmund majority did not say that those who "kill" are eligible only if they intend death, but neither did it say they are eligible regardless of their mental state. The Tison majority concluded that Enmund "held" that capital punishment could be imposed on "the felony murderer who actually killed," (5) but only "when the circumstances warranted." (6) Because both cases concerned accomplices of intentional killers, neither Court specified whether those who "killed" included all who caused death, by any means, and with any mental state. Yet most lower courts have assumed that anyone causing death in a predicate felony is death-eligible, regardless of any culpability. Omitting consideration of a culpable mental state is at odds with a central background principle of Eighth Amendment law: that we may only execute people to advance deterrence and retribution and that neither can be furthered if the person does not act with culpability. …
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capital punishment of unintentional felony murder
Social Science Research Network, 2017Co-Authors: Guyora Binder, Robert Weisberg, Brenner M FissellAbstract:Under the prevailing interpretation of the Eighth Amendment in the lower courts, a defendant who causes a death inadvertently in the course of a felony is eligible for capital punishment. This unfortunate interpretation rests on an unduly mechanical reading of the Supreme Court’s decisions in Enmund v. Florida and Tison v. Arizona, which require culpability for capital punishment of co-felons who do not kill. The lower courts have drawn the unwarranted inference that these cases permit execution of those who cause death without any culpability towards death. This Article shows that this mechanical reading of precedent is mistaken, because the underlying justifications of Eighth Amendment jurisprudence require a rational selection for death of only the most deserving and deterrable offenders, and this in turn requires an assessment of culpability. We argue that the Supreme Court should address this open question in Eighth Amendment law and that it should correct the lower courts by imposing a Uniform Requirement of at least recklessness with respect to death for capital punishment of felony murder.
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capital punishment of unintentional felony murder
Notre Dame Law Review, 2017Co-Authors: Guyora Binder, Brenner M Fissell, Robert WeisbergAbstract:Under the prevailing interpretation of the Eighth Amendment in the lower courts, a defendant who causes a death inadvertently in the course of a felony is eligible for capital punishment. This unfortunate interpretation rests on an unduly mechanical reading of the Supreme Court's decisions in Enmund v. Florida and Tison v. Arizona, which require culpability for capital punishment of co-felons who do not kill. The lower courts have drawn the unwarranted inference that these cases permit execution of those who cause death without any culpability towards death. This Article shows that this mechanical reading of precedent is mistaken, because the underlying justifications of Eighth Amendment jurisprudence require a rational selection for death of only the most deserving and deferrable offenders, and this in turn requires an assessment of culpability. We argue that the Supreme Court should address this open question in Eighth Amendment law and that it should correct the lower courts by imposing a Uniform Requirement of at least recklessness with respect to death for capital punishment of felony murder. INTRODUCTION That a defendant could be executed for causing death inadvertently might seem absurd. Nevertheless, the great majority of American courts to have considered the question have concluded that the Eighth Amendment of the U.S. Constitution permits such executions. In so doing, they have interpreted Supreme Court doctrine to allow capital punishment of any person who causes death during the commission of a felony, regardless of that person's mental state with respect to the resultant death. Under this reading of precedent, the following defendants are eligible for the death penalty: the driver of a getaway car who kills a jaywalker, the burglar who starles an elderly homeowner and causes a fatal heart attack, and the robber who unknowingly punches a hemophiliac. Such counterintuitive results become conceivable when eligibility for the death penalty is untethered from the defendant's culpability. This disconnect results from an overly mechanical interpretation of the Supreme Court's two key cases applying the Eighth Amendment to the felony murder context: Enmund v. Florida (1) and Tison v. Arizona. (2) Although these cases have been read to permit execution of nonculpable killers, the holdings of both decisions impose a high level of culpability for execution of accomplices in felony murder, on the ground that death should be reserved for the most culpable offenders. In overturning the death sentence of an accomplice in a fatal felony, the Enmund majority stated that a participant in a fatal felony is ineligible for capital punishment if he "does not himself kill, attempt to kill, or intend that a killing take place or that lethal force will be employed." (3) In upholding the death sentences of two accomplices in a fatal felony, the Tison majority permitted capital punishment of felons "whose participation is major and whose mental state is one of reckless indifference to the value of human life." (4) Thus, subsequent readings of Enmund and Tison that permit the execution of actual killers regardless of culpability are largely based on what they did not say about a question that was not before them. To be sure, the Enmund majority did not say that those who "kill" are eligible only if they intend death, but neither did it say they are eligible regardless of their mental state. The Tison majority concluded that Enmund "held" that capital punishment could be imposed on "the felony murderer who actually killed," (5) but only "when the circumstances warranted." (6) Because both cases concerned accomplices of intentional killers, neither Court specified whether those who "killed" included all who caused death, by any means, and with any mental state. Yet most lower courts have assumed that anyone causing death in a predicate felony is death-eligible, regardless of any culpability. Omitting consideration of a culpable mental state is at odds with a central background principle of Eighth Amendment law: that we may only execute people to advance deterrence and retribution and that neither can be furthered if the person does not act with culpability. …
Brooks R Robey - One of the best experts on this subject based on the ideXlab platform.
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regulation of mesangial cell hexokinase activity and expression by heparin binding epidermal growth factor like growth factor epidermal growth factors and phorbol esters increase glucose metabolism via a common mechanism involving classic mitogen activated protein kinase pathway activation and induction of hexokinase ii expression
Journal of Biological Chemistry, 2002Co-Authors: Brooks R Robey, Anna V P Santos, Oscar Noboa, Jane M BrysonAbstract:Heparin-binding epidermal growth factor -like growth factor (HB-EGF) expression and hexokinase (HK) activity are increased in various pathologic renal conditions. Although the mitogenic properties of HB-EGF have been well characterized, its effects on glucose (Glc) metabolism have not. We therefore examined the possibility that HB-EGF might regulate HK activity and expression in glomerular mesangial cells, which constitute the principal renal cell type affected by a variety of pathologic conditions. Protein kinase C (PKC)-dependent classic mitogen-activated protein kinase (MAPK) pathway activation has been associated with increased HK activity in this cell type, so we also examined dependence upon these signaling intermediates. HB-EGF (> or =10 nm) increased total HK activity over 50% within 12-24 h, an effect mimicked by other EGF receptor agonists, but not by IGF-1 or elevated Glc. EGF receptor and classic MAPK pathway antagonists prevented this increase, as did general inhibitors of gene transcription and protein synthesis. Both HB-EGF and phorbol esters activated the classic MAPK pathway, albeit via PKC-independent and PKC-dependent mechanisms, respectively. Both stimuli were associated with increased HK activity, selectively increased HKII isoform expression, and increased Glc metabolism via both the glycolytic-tricarboxylic acid cycle route and the pentose phosphate pathway. HB-EGF thus constitutes a novel regulator of mesangial cell HK activity and Glc metabolism. HKII is the principal regulated isoform in these cells, as it is in insulin-sensitive peripheral tissues, such as muscle. However, the Uniform Requirement for classic MAPK pathway activation distinguishes HKII regulation in mesangial cells from that observed in muscle. These findings suggest a novel mechanism whereby growth factors may couple metabolism to glomerular injury.
