Skip to main content
Advertisement

Main menu

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Special Sections
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Submit
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET

User menu

  • My alerts
  • Log in
  • My Cart

Search

  • Advanced search
Journal of Pharmacology and Experimental Therapeutics
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET
  • My alerts
  • Log in
  • My Cart
Journal of Pharmacology and Experimental Therapeutics

Advanced Search

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Special Sections
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Submit
  • Visit jpet on Facebook
  • Follow jpet on Twitter
  • Follow jpet on LinkedIn
Research ArticleEndocrine and Diabetes

Pharmacological Inhibition of Mitochondrial Carbonic Anhydrases Protects Mouse Cerebral Pericytes from High Glucose-Induced Oxidative Stress and Apoptosis

Gul N. Shah, Tulin O. Price, William A. Banks, Yoichi Morofuji, Andrej Kovac, Nuran Ercal, Christine M. Sorenson, Eui S. Shin and Nader Sheibani
Journal of Pharmacology and Experimental Therapeutics March 2013, 344 (3) 637-645; DOI: https://doi.org/10.1124/jpet.112.201400
Gul N. Shah
Division of Endocrinology, Department of Internal Medicine, Saint Louis University, Edward A. Doisy Research Center, St. Louis, Missouri (G.N.S., T.O.P.); Veterans Affairs Puget Sound Health Care System, Geriatric Research, Education and Clinical Center, Seattle, Washington (W.A.B.); Division of Gerontology and Geriatric Medicine, Department of Medicine, University of Washington, Seattle, Washington (W.A.B., Y.M., A.K.); Department of Chemistry, Missouri University of Science and Technology, Rolla, Missouri (N.E.); and Departments of Pediatrics (C.M.S.) and Ophthalmology and Visual Sciences (E.S.S., N.S.), University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Tulin O. Price
Division of Endocrinology, Department of Internal Medicine, Saint Louis University, Edward A. Doisy Research Center, St. Louis, Missouri (G.N.S., T.O.P.); Veterans Affairs Puget Sound Health Care System, Geriatric Research, Education and Clinical Center, Seattle, Washington (W.A.B.); Division of Gerontology and Geriatric Medicine, Department of Medicine, University of Washington, Seattle, Washington (W.A.B., Y.M., A.K.); Department of Chemistry, Missouri University of Science and Technology, Rolla, Missouri (N.E.); and Departments of Pediatrics (C.M.S.) and Ophthalmology and Visual Sciences (E.S.S., N.S.), University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
William A. Banks
Division of Endocrinology, Department of Internal Medicine, Saint Louis University, Edward A. Doisy Research Center, St. Louis, Missouri (G.N.S., T.O.P.); Veterans Affairs Puget Sound Health Care System, Geriatric Research, Education and Clinical Center, Seattle, Washington (W.A.B.); Division of Gerontology and Geriatric Medicine, Department of Medicine, University of Washington, Seattle, Washington (W.A.B., Y.M., A.K.); Department of Chemistry, Missouri University of Science and Technology, Rolla, Missouri (N.E.); and Departments of Pediatrics (C.M.S.) and Ophthalmology and Visual Sciences (E.S.S., N.S.), University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Yoichi Morofuji
Division of Endocrinology, Department of Internal Medicine, Saint Louis University, Edward A. Doisy Research Center, St. Louis, Missouri (G.N.S., T.O.P.); Veterans Affairs Puget Sound Health Care System, Geriatric Research, Education and Clinical Center, Seattle, Washington (W.A.B.); Division of Gerontology and Geriatric Medicine, Department of Medicine, University of Washington, Seattle, Washington (W.A.B., Y.M., A.K.); Department of Chemistry, Missouri University of Science and Technology, Rolla, Missouri (N.E.); and Departments of Pediatrics (C.M.S.) and Ophthalmology and Visual Sciences (E.S.S., N.S.), University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Andrej Kovac
Division of Endocrinology, Department of Internal Medicine, Saint Louis University, Edward A. Doisy Research Center, St. Louis, Missouri (G.N.S., T.O.P.); Veterans Affairs Puget Sound Health Care System, Geriatric Research, Education and Clinical Center, Seattle, Washington (W.A.B.); Division of Gerontology and Geriatric Medicine, Department of Medicine, University of Washington, Seattle, Washington (W.A.B., Y.M., A.K.); Department of Chemistry, Missouri University of Science and Technology, Rolla, Missouri (N.E.); and Departments of Pediatrics (C.M.S.) and Ophthalmology and Visual Sciences (E.S.S., N.S.), University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Nuran Ercal
Division of Endocrinology, Department of Internal Medicine, Saint Louis University, Edward A. Doisy Research Center, St. Louis, Missouri (G.N.S., T.O.P.); Veterans Affairs Puget Sound Health Care System, Geriatric Research, Education and Clinical Center, Seattle, Washington (W.A.B.); Division of Gerontology and Geriatric Medicine, Department of Medicine, University of Washington, Seattle, Washington (W.A.B., Y.M., A.K.); Department of Chemistry, Missouri University of Science and Technology, Rolla, Missouri (N.E.); and Departments of Pediatrics (C.M.S.) and Ophthalmology and Visual Sciences (E.S.S., N.S.), University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Christine M. Sorenson
Division of Endocrinology, Department of Internal Medicine, Saint Louis University, Edward A. Doisy Research Center, St. Louis, Missouri (G.N.S., T.O.P.); Veterans Affairs Puget Sound Health Care System, Geriatric Research, Education and Clinical Center, Seattle, Washington (W.A.B.); Division of Gerontology and Geriatric Medicine, Department of Medicine, University of Washington, Seattle, Washington (W.A.B., Y.M., A.K.); Department of Chemistry, Missouri University of Science and Technology, Rolla, Missouri (N.E.); and Departments of Pediatrics (C.M.S.) and Ophthalmology and Visual Sciences (E.S.S., N.S.), University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Eui S. Shin
Division of Endocrinology, Department of Internal Medicine, Saint Louis University, Edward A. Doisy Research Center, St. Louis, Missouri (G.N.S., T.O.P.); Veterans Affairs Puget Sound Health Care System, Geriatric Research, Education and Clinical Center, Seattle, Washington (W.A.B.); Division of Gerontology and Geriatric Medicine, Department of Medicine, University of Washington, Seattle, Washington (W.A.B., Y.M., A.K.); Department of Chemistry, Missouri University of Science and Technology, Rolla, Missouri (N.E.); and Departments of Pediatrics (C.M.S.) and Ophthalmology and Visual Sciences (E.S.S., N.S.), University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Nader Sheibani
Division of Endocrinology, Department of Internal Medicine, Saint Louis University, Edward A. Doisy Research Center, St. Louis, Missouri (G.N.S., T.O.P.); Veterans Affairs Puget Sound Health Care System, Geriatric Research, Education and Clinical Center, Seattle, Washington (W.A.B.); Division of Gerontology and Geriatric Medicine, Department of Medicine, University of Washington, Seattle, Washington (W.A.B., Y.M., A.K.); Department of Chemistry, Missouri University of Science and Technology, Rolla, Missouri (N.E.); and Departments of Pediatrics (C.M.S.) and Ophthalmology and Visual Sciences (E.S.S., N.S.), University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF + SI
  • PDF
Loading

Abstract

Diabetes-associated complications in the microvasculature of the brain are caused by oxidative stress, generated by overproduction of reactive oxygen species from hyperglycemia-induced accelerated oxidative metabolism of glucose. Pericytes, essential for the viability of the microvasculature, are especially susceptible to oxidative stress. Mitochondrial carbonic anhydrases, regulators of the oxidative metabolism of glucose, determine the rate of reactive oxygen species production and inhibition of mitochondrial carbonic anhydrases rescues glucose-induced pericyte loss in the diabetic mouse brain. We hypothesized that high glucose induces intracellular oxidative stress and pericyte apoptosis and that inhibition of mitochondrial carbonic anhydrases protects pericytes from oxidative stress-induced apoptosis. To validate our hypothesis, conditionally immortalized cerebral pericyte (IPC) cultures were established from Immortomice to investigate the effect of high glucose on oxidative stress and pericyte apoptosis. The IPCs expressed pericyte markers and induced high transendothelial electrical resistance and low permeability in brain endothelial cell monolayers comparable with pericytes in primary cultures. The IPCs also secreted cytokines constitutively and in response to lipopolysaccharide similar to pericytes. High glucose caused oxidative stress and apoptosis of these cells, with both oxidative stress and apoptosis significantly reduced after mitochondrial carbonic anhydrase inhibition. These results provide the first evidence that pharmacological inhibition of mitochondrial carbonic anhydrases attenuates pericyte apoptosis caused by high glucose-induced oxidative stress. Carbonic anhydrase inhibitors have a long history of safe clinical use and can be immediately evaluated for this new indication in translational research. Thus, mitochondrial carbonic anhydrases may provide a new therapeutic target for oxidative stress-related illnesses of the brain.

Footnotes

  • This study was supported by the National Institutes of Health [Grants R01-DK083485, RC4-EY021357, EY016695, P30-EY016665, and P30-CA014520].

  • dx.doi.org/10.1124/jpet.112.201400.

  • ↵Embedded ImageThis article has supplemental material available at jpet.aspetjournals.org.

  • Received October 26, 2012.
  • Accepted December 14, 2012.
  • U.S. Government work not protected by U.S. copyright
View Full Text

JPET articles become freely available 12 months after publication, and remain freely available for 5 years. 

Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page. 

 

  • Click here for information on institutional subscriptions.
  • Click here for information on individual ASPET membership.

 

Log in using your username and password

Forgot your user name or password?

Purchase access

You may purchase access to this article. This will require you to create an account if you don't already have one.
PreviousNext
Back to top

In this issue

Journal of Pharmacology and Experimental Therapeutics: 344 (3)
Journal of Pharmacology and Experimental Therapeutics
Vol. 344, Issue 3
1 Mar 2013
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover
  • Index by author
  • Editorial Board (PDF)
  • Front Matter (PDF)
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this Journal of Pharmacology and Experimental Therapeutics article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
Pharmacological Inhibition of Mitochondrial Carbonic Anhydrases Protects Mouse Cerebral Pericytes from High Glucose-Induced Oxidative Stress and Apoptosis
(Your Name) has forwarded a page to you from Journal of Pharmacology and Experimental Therapeutics
(Your Name) thought you would be interested in this article in Journal of Pharmacology and Experimental Therapeutics.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Research ArticleEndocrine and Diabetes

Mitochondrial CA Inhibition Protects Apoptosis of Brain PCs

Gul N. Shah, Tulin O. Price, William A. Banks, Yoichi Morofuji, Andrej Kovac, Nuran Ercal, Christine M. Sorenson, Eui S. Shin and Nader Sheibani
Journal of Pharmacology and Experimental Therapeutics March 1, 2013, 344 (3) 637-645; DOI: https://doi.org/10.1124/jpet.112.201400

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero

Share
Research ArticleEndocrine and Diabetes

Mitochondrial CA Inhibition Protects Apoptosis of Brain PCs

Gul N. Shah, Tulin O. Price, William A. Banks, Yoichi Morofuji, Andrej Kovac, Nuran Ercal, Christine M. Sorenson, Eui S. Shin and Nader Sheibani
Journal of Pharmacology and Experimental Therapeutics March 1, 2013, 344 (3) 637-645; DOI: https://doi.org/10.1124/jpet.112.201400
del.icio.us logo Digg logo Reddit logo Twitter logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • Introduction
    • Materials and Methods
    • Results
    • Discussion
    • Acknowledgments
    • Authorship Contributions
    • Footnotes
    • Abbreviations
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF + SI
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • PF-5190457 metabolite activity at the ghrelin receptor
  • Insulin Inhibits Ubiquitination via USP14.
  • Characterization of a Novel Weekly Basal Insulin
Show more Endocrine and Diabetes

Similar Articles

Advertisement
  • Home
  • Alerts
Facebook   Twitter   LinkedIn   RSS

Navigate

  • Current Issue
  • Fast Forward by date
  • Fast Forward by section
  • Latest Articles
  • Archive
  • Search for Articles
  • Feedback
  • ASPET

More Information

  • About JPET
  • Editorial Board
  • Instructions to Authors
  • Submit a Manuscript
  • Customized Alerts
  • RSS Feeds
  • Subscriptions
  • Permissions
  • Terms & Conditions of Use

ASPET's Other Journals

  • Drug Metabolism and Disposition
  • Molecular Pharmacology
  • Pharmacological Reviews
  • Pharmacology Research & Perspectives
ISSN 1521-0103 (Online)

Copyright © 2023 by the American Society for Pharmacology and Experimental Therapeutics