Protein kinase B (Akt) and mitogen-activated protein kinase p38α in retinal ischemic post-conditioning

John C. Dreixler; Ajay Sampat; Afzhal R. Shaikh; Michael Alexander; Marcus M. Marcet; Steven Roth

doi:10.1007/s12031-011-9523-5

Protein kinase B (Akt) and mitogen-activated protein kinase p38α in retinal ischemic post-conditioning

John C. Dreixler, Ajay Sampat, Afzhal R. Shaikh, Michael Alexander, Marcus M. Marcet, Steven Roth^*

^*Corresponding author for this work

Medicine, Pulmonary Division

Research output: Contribution to journal › Article › peer-review

9 Scopus citations

Abstract

In previous studies, it was shown that post-conditioning, a transient period of brief ischemia following prolonged severe ischemia in the retina, could provide significant improvement in post-ischemic recovery, attenuation of cell loss, and decreased apoptosis. However, the mechanisms of post-conditioning in the retina have not been elucidated. We hypothesized that two kinases, mitogen-activated protein kinase p38α and protein kinase B (Akt), were involved in the mechanism of post-conditioning. Ischemia was induced in rat retina in vivo. Recovery after ischemia followed by 8 min of post-conditioning early in the reperfusion period after prolonged ischemia was assessed functionally (electroretinography) and histologically at 7 days after ischemia. We examined the role of p38α and Akt subtypes 1-3 in post-conditioning by intravitreal injection of interfering RNA 6 h prior to ischemia and post-conditioning and compared the results to injection of non-silencing interfering RNA sequence. The blockade of p38α significantly decreased the recovery after ischemia and post-conditioning, and enhanced cell loss and disorganization of the retina. Blockade of Akt1, and to a lesser degree, Akt2, significantly decreased the recovery after ischemia and enhanced cell loss and disorganization. These differences in the effects of blockade of Akt subtypes were not explainable by distribution of Akt subtypes in the retina, which were similar. In conclusion, both p38 and Akt are essential components of the neuroprotection induced by post-ischemic conditioning in the retina.

Original language	English (US)
Pages (from-to)	309-320
Number of pages	12
Journal	Journal of Molecular Neuroscience
Volume	45
Issue number	2
DOIs	https://doi.org/10.1007/s12031-011-9523-5
State	Published - Oct 2011

Funding

Acknowledgments Supported by National Institutes of Health (Rockville, MD) grants RO1 EY10343 and RO1 EY10343-16S2 (American Recovery and Reinvestment Act) to Dr. Roth, AG029795-02 for the Medical Student Summer Research Program at the Pritzker School of Medicine, UL1RR024999 to the University of Chicago Institute for Translational Medicine; the Illinois Society for the Prevention of Blindness (Chicago, IL); and the Dean’s Research Advisory Committee of the Division of Biological Sciences of the University of Chicago. Ajay Sampat was the recipient of a Medical Student Research Fellowship Award from the American Academy of Neurology, St Paul, MN. There is no conflict of interest or commercial interest for any of the authors.

Keywords

Akt
Post-conditioning
Retinal ischemia
p38

ASJC Scopus subject areas

Cellular and Molecular Neuroscience

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10.1007/s12031-011-9523-5

Cite this

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title = "Protein kinase B (Akt) and mitogen-activated protein kinase p38α in retinal ischemic post-conditioning",

abstract = "In previous studies, it was shown that post-conditioning, a transient period of brief ischemia following prolonged severe ischemia in the retina, could provide significant improvement in post-ischemic recovery, attenuation of cell loss, and decreased apoptosis. However, the mechanisms of post-conditioning in the retina have not been elucidated. We hypothesized that two kinases, mitogen-activated protein kinase p38α and protein kinase B (Akt), were involved in the mechanism of post-conditioning. Ischemia was induced in rat retina in vivo. Recovery after ischemia followed by 8 min of post-conditioning early in the reperfusion period after prolonged ischemia was assessed functionally (electroretinography) and histologically at 7 days after ischemia. We examined the role of p38α and Akt subtypes 1-3 in post-conditioning by intravitreal injection of interfering RNA 6 h prior to ischemia and post-conditioning and compared the results to injection of non-silencing interfering RNA sequence. The blockade of p38α significantly decreased the recovery after ischemia and post-conditioning, and enhanced cell loss and disorganization of the retina. Blockade of Akt1, and to a lesser degree, Akt2, significantly decreased the recovery after ischemia and enhanced cell loss and disorganization. These differences in the effects of blockade of Akt subtypes were not explainable by distribution of Akt subtypes in the retina, which were similar. In conclusion, both p38 and Akt are essential components of the neuroprotection induced by post-ischemic conditioning in the retina.",

keywords = "Akt, Post-conditioning, Retinal ischemia, p38",

author = "Dreixler, {John C.} and Ajay Sampat and Shaikh, {Afzhal R.} and Michael Alexander and Marcet, {Marcus M.} and Steven Roth",

note = "Funding Information: Acknowledgments Supported by National Institutes of Health (Rockville, MD) grants RO1 EY10343 and RO1 EY10343-16S2 (American Recovery and Reinvestment Act) to Dr. Roth, AG029795-02 for the Medical Student Summer Research Program at the Pritzker School of Medicine, UL1RR024999 to the University of Chicago Institute for Translational Medicine; the Illinois Society for the Prevention of Blindness (Chicago, IL); and the Dean{\textquoteright}s Research Advisory Committee of the Division of Biological Sciences of the University of Chicago. Ajay Sampat was the recipient of a Medical Student Research Fellowship Award from the American Academy of Neurology, St Paul, MN. There is no conflict of interest or commercial interest for any of the authors.",

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AU - Marcet, Marcus M.

AU - Roth, Steven

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N2 - In previous studies, it was shown that post-conditioning, a transient period of brief ischemia following prolonged severe ischemia in the retina, could provide significant improvement in post-ischemic recovery, attenuation of cell loss, and decreased apoptosis. However, the mechanisms of post-conditioning in the retina have not been elucidated. We hypothesized that two kinases, mitogen-activated protein kinase p38α and protein kinase B (Akt), were involved in the mechanism of post-conditioning. Ischemia was induced in rat retina in vivo. Recovery after ischemia followed by 8 min of post-conditioning early in the reperfusion period after prolonged ischemia was assessed functionally (electroretinography) and histologically at 7 days after ischemia. We examined the role of p38α and Akt subtypes 1-3 in post-conditioning by intravitreal injection of interfering RNA 6 h prior to ischemia and post-conditioning and compared the results to injection of non-silencing interfering RNA sequence. The blockade of p38α significantly decreased the recovery after ischemia and post-conditioning, and enhanced cell loss and disorganization of the retina. Blockade of Akt1, and to a lesser degree, Akt2, significantly decreased the recovery after ischemia and enhanced cell loss and disorganization. These differences in the effects of blockade of Akt subtypes were not explainable by distribution of Akt subtypes in the retina, which were similar. In conclusion, both p38 and Akt are essential components of the neuroprotection induced by post-ischemic conditioning in the retina.

AB - In previous studies, it was shown that post-conditioning, a transient period of brief ischemia following prolonged severe ischemia in the retina, could provide significant improvement in post-ischemic recovery, attenuation of cell loss, and decreased apoptosis. However, the mechanisms of post-conditioning in the retina have not been elucidated. We hypothesized that two kinases, mitogen-activated protein kinase p38α and protein kinase B (Akt), were involved in the mechanism of post-conditioning. Ischemia was induced in rat retina in vivo. Recovery after ischemia followed by 8 min of post-conditioning early in the reperfusion period after prolonged ischemia was assessed functionally (electroretinography) and histologically at 7 days after ischemia. We examined the role of p38α and Akt subtypes 1-3 in post-conditioning by intravitreal injection of interfering RNA 6 h prior to ischemia and post-conditioning and compared the results to injection of non-silencing interfering RNA sequence. The blockade of p38α significantly decreased the recovery after ischemia and post-conditioning, and enhanced cell loss and disorganization of the retina. Blockade of Akt1, and to a lesser degree, Akt2, significantly decreased the recovery after ischemia and enhanced cell loss and disorganization. These differences in the effects of blockade of Akt subtypes were not explainable by distribution of Akt subtypes in the retina, which were similar. In conclusion, both p38 and Akt are essential components of the neuroprotection induced by post-ischemic conditioning in the retina.

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Protein kinase B (Akt) and mitogen-activated protein kinase p38α in retinal ischemic post-conditioning

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