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| IJCEM Copyright © 2008-All rights reserved. Published by e-Century Publishing Corporation, Madison, WI 53711 |
Int J Clin Exp Med 2(2):149-158;2009
Original Article
Regulation of intracellular calcium in cortical neurons
Najeeb A Shirwany, Jun Xie, Qing Guo
Department of Physiology; University of Oklahoma Health Sciences Center; Oklahoma City, OK 73014, USA.
Received May 25, 2009; accepted June 6, 2009; available online June 12, 2009
Abstract: The pathogenesis of Alzheimer’s Disease (AD) is not fully understood. Amyloid plaques could be causally linked to neuronal
loss in AD. Two proteolytic products of the Amyloid Precursor Protein (APP), Amyloid β40 (Aβ40) and Amyloid β42 (Aβ42), are
considered to be critical in the neurodegeneration seen in AD. However, in transgenic mice that overexpress human Aβ40 or Aβ42, it
was shown that Aβ42 was much more amyloidogenic than Aβ40. In contrast to this observation, we have found that cultured cortical
neurons from mice transgenic for human Aβ40 and for Aβ42 are both and statistically equally vulnerable to nutritive challenge induced
by trophic factor withdrawal (TFW). Aberrant regulation of InsP3R (Inositol triphosphate receptor)-mediated calcium release has been
implicated in neuronal cell death. It is however not clear whether this pathway plays a critical role in cortical neurons transgenic for
different species of human Aβ. We now report that Aβ40 and Aβ42 equally exacerbated intracellular calcium response to TFW in
cortical neurons following TFW. When bradykinin (BK), a potent stimulant of InsP3R-mediated calcium release from ER, was applied to
these cells, wild type (WT) neurons exhibited a steep rise in [Ca2+]i but this was not observed in either Aβ transgenic type. Similarly,
when 1 μM Xestopongin C (XeC), a specific blocker of InsP3R, was applied to these neurons, WT cells showed a significant
attenuation of increase in [Ca2+]i following TFW, while elevation in [Ca2+]i induced by TFW remained largely unchanged in Aβ40 and
Aβ42 cells. Finally, when we treated these cells with a Ca2+ chelator (BAPTA; 10 μM), all three cell types had a marked attenuation of
[Ca2+]i. These findings indicate that the exacerbated calcium dysregulation following TFW in Aβ transgenic neurons are likely to be
mediated by calcium channels other than ER InsP3R receptors. Overall, our results also suggest that a highly amyloidogenic Abeta
species, such as Aβ42, might not necessarily be significantly more neurotoxic than a less or non-amyloidogenic Abeta species, such
as Aβ40. (IJCEM905002).
Key Words: Saphenous vein graft disease, endothelium, thrombosis, subendothelium, atherosclerosis
Full Text PDF
Address all correspondence to:
Najeeb A Shirwany, M.D., or Qing Guo, MD, PhD
Department of Physiology
The University of Oklahoma Health Sciences Center
940 Stanton L. Young Blvd., BMSB Rm.607
Oklahoma City, OK 73104, USA
Tel: (405) 271-2226 ext. 56268, FAX: (405) 271-3181
E-mails: Najeeb-shirwany@ouhsc.edu; Or qing-guo@ouhc.edu
Original Article
Regulation of intracellular calcium in cortical neurons
Najeeb A Shirwany, Jun Xie, Qing Guo
Department of Physiology; University of Oklahoma Health Sciences Center; Oklahoma City, OK 73014, USA.
Received May 25, 2009; accepted June 6, 2009; available online June 12, 2009
Abstract: The pathogenesis of Alzheimer’s Disease (AD) is not fully understood. Amyloid plaques could be causally linked to neuronal
loss in AD. Two proteolytic products of the Amyloid Precursor Protein (APP), Amyloid β40 (Aβ40) and Amyloid β42 (Aβ42), are
considered to be critical in the neurodegeneration seen in AD. However, in transgenic mice that overexpress human Aβ40 or Aβ42, it
was shown that Aβ42 was much more amyloidogenic than Aβ40. In contrast to this observation, we have found that cultured cortical
neurons from mice transgenic for human Aβ40 and for Aβ42 are both and statistically equally vulnerable to nutritive challenge induced
by trophic factor withdrawal (TFW). Aberrant regulation of InsP3R (Inositol triphosphate receptor)-mediated calcium release has been
implicated in neuronal cell death. It is however not clear whether this pathway plays a critical role in cortical neurons transgenic for
different species of human Aβ. We now report that Aβ40 and Aβ42 equally exacerbated intracellular calcium response to TFW in
cortical neurons following TFW. When bradykinin (BK), a potent stimulant of InsP3R-mediated calcium release from ER, was applied to
these cells, wild type (WT) neurons exhibited a steep rise in [Ca2+]i but this was not observed in either Aβ transgenic type. Similarly,
when 1 μM Xestopongin C (XeC), a specific blocker of InsP3R, was applied to these neurons, WT cells showed a significant
attenuation of increase in [Ca2+]i following TFW, while elevation in [Ca2+]i induced by TFW remained largely unchanged in Aβ40 and
Aβ42 cells. Finally, when we treated these cells with a Ca2+ chelator (BAPTA; 10 μM), all three cell types had a marked attenuation of
[Ca2+]i. These findings indicate that the exacerbated calcium dysregulation following TFW in Aβ transgenic neurons are likely to be
mediated by calcium channels other than ER InsP3R receptors. Overall, our results also suggest that a highly amyloidogenic Abeta
species, such as Aβ42, might not necessarily be significantly more neurotoxic than a less or non-amyloidogenic Abeta species, such
as Aβ40. (IJCEM905002).
Key Words: Saphenous vein graft disease, endothelium, thrombosis, subendothelium, atherosclerosis
Full Text PDF
Address all correspondence to:
Najeeb A Shirwany, M.D., or Qing Guo, MD, PhD
Department of Physiology
The University of Oklahoma Health Sciences Center
940 Stanton L. Young Blvd., BMSB Rm.607
Oklahoma City, OK 73104, USA
Tel: (405) 271-2226 ext. 56268, FAX: (405) 271-3181
E-mails: Najeeb-shirwany@ouhsc.edu; Or qing-guo@ouhc.edu
