TAL (transaldolase) was originally described in the yeast as an enzyme of the PPP (pentose phosphate pathway). However, certain organisms and mammalian tissues lack TAL, and the overall reason for its existence is unclear. Recently, deletion of Ser171 (TALΔS171) was found in five patients causing inactivation, proteasome-mediated degradation and complete deficiency of TAL. In the present study, microarray and follow-up Western-blot, enzyme-activity and metabolic studies of TALΔS171 TD (TAL-deficient) lymphoblasts revealed co-ordinated changes in the expression of genes involved in the PPP, mitochondrial biogenesis, oxidative stress, and Ca2+ fluxing. Sedoheptulose 7-phosphate was accumulated, whereas G6P (glucose 6-phosphate) was depleted, indicating a failure to recycle G6P for the oxidative branch of the PPP. Nucleotide analysis showed depletion of NADPH and NAD+ and accumulation of ADP-ribose. TD cells have diminished Δψm (mitochondrial transmembrane potential) and increased mitochondrial mass associated with increased production of nitric oxide and ATP. TAL deficiency resulted in enhanced spontaneous and H2O2-induced apoptosis. TD lymphoblasts showed increased expression of CD38, which hydrolyses NAD+ into ADP-ribose, a trigger of Ca2+ release from the endoplasmic reticulum that, in turn, facilitated CD20-induced apoptosis. By contrast, TD cells were resistant to CD95/Fas-induced apoptosis, owing to a dependence of caspase activity on redox-sensitive cysteine residues. Normalization of TAL activity by adeno-associated-virus-mediated gene transfer reversed the elevated CD38 expression, ATP and Ca2+ levels, suppressed H2O2- and CD20-induced apoptosis and enhanced Fas-induced cell death. The present study identified the TAL deficiency as a modulator of mitochondrial homoeostasis, Ca2+ fluxing and apoptosis.
Skip Nav Destination
Follow us on Twitter @Biochem_Journal
Article navigation
October 2008
-
Cover Image
Cover Image
- PDF Icon PDF LinkFront Matter
- PDF Icon PDF LinkTable of Contents
- PDF Icon PDF LinkEditorial Board
Research Article|
September 12 2008
Transaldolase deficiency influences the pentose phosphate pathway, mitochondrial homoeostasis and apoptosis signal processing Available to Purchase
Yueming Qian;
Yueming Qian
*Department of Medicine, SUNY Upstate Medical University, Syracuse, NY 13210, U.S.A.
Search for other works by this author on:
Sanjay Banerjee;
Sanjay Banerjee
*Department of Medicine, SUNY Upstate Medical University, Syracuse, NY 13210, U.S.A.
Search for other works by this author on:
Craig E. Grossman;
Craig E. Grossman
*Department of Medicine, SUNY Upstate Medical University, Syracuse, NY 13210, U.S.A.
†Department of Microbiology and Immunology, SUNY Upstate Medical University, Syracuse, NY 13210, U.S.A.
Search for other works by this author on:
Wendy Amidon;
Wendy Amidon
*Department of Medicine, SUNY Upstate Medical University, Syracuse, NY 13210, U.S.A.
Search for other works by this author on:
Gyorgy Nagy;
Gyorgy Nagy
*Department of Medicine, SUNY Upstate Medical University, Syracuse, NY 13210, U.S.A.
Search for other works by this author on:
Maureen Barcza;
Maureen Barcza
‡Department of Physiology, SUNY Upstate Medical University, Syracuse, NY 13210, U.S.A.
Search for other works by this author on:
Brian Niland;
Brian Niland
*Department of Medicine, SUNY Upstate Medical University, Syracuse, NY 13210, U.S.A.
†Department of Microbiology and Immunology, SUNY Upstate Medical University, Syracuse, NY 13210, U.S.A.
Search for other works by this author on:
David R. Karp;
David R. Karp
§University of Texas Southwestern Medical Center, Dallas, TX 75390, U.S.A.
Search for other works by this author on:
Frank A. Middleton;
Frank A. Middleton
‡Department of Physiology, SUNY Upstate Medical University, Syracuse, NY 13210, U.S.A.
Search for other works by this author on:
Katalin Banki;
Katalin Banki
∥Department of Pathology, SUNY Upstate Medical University, Syracuse, NY 13210, U.S.A.
Search for other works by this author on:
Andras Perl
Andras Perl
1
*Department of Medicine, SUNY Upstate Medical University, Syracuse, NY 13210, U.S.A.
†Department of Microbiology and Immunology, SUNY Upstate Medical University, Syracuse, NY 13210, U.S.A.
1To whom correspondence should be addressed (email [email protected]).
Search for other works by this author on:
Publisher: Portland Press Ltd
Received:
April 07 2008
Revision Received:
May 19 2008
Accepted:
May 22 2008
Accepted Manuscript online:
May 22 2008
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2008 Biochemical Society
2008
Biochem J (2008) 415 (1): 123–134.
Article history
Received:
April 07 2008
Revision Received:
May 19 2008
Accepted:
May 22 2008
Accepted Manuscript online:
May 22 2008
Citation
Yueming Qian, Sanjay Banerjee, Craig E. Grossman, Wendy Amidon, Gyorgy Nagy, Maureen Barcza, Brian Niland, David R. Karp, Frank A. Middleton, Katalin Banki, Andras Perl; Transaldolase deficiency influences the pentose phosphate pathway, mitochondrial homoeostasis and apoptosis signal processing. Biochem J 1 October 2008; 415 (1): 123–134. doi: https://doi.org/10.1042/BJ20080722
Download citation file:
Sign in
Don't already have an account? Register
Sign in to your personal account
You could not be signed in. Please check your email address / username and password and try again.
Could not validate captcha. Please try again.
Biochemical Society Member Sign in
Sign InSign in via your Institution
Sign in via your InstitutionGet Access To This Article
Follow us on Twitter @Biochem_Journal
Open Access for all
We offer compliant routes for all authors from 2025. With library support, there will be no author nor reader charges in 5 journals. Check here |
![]() View past webinars > |