PMID- 10329680
OWN - NLM
STAT- MEDLINE
DCOM- 19990709
LR  - 20190508
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 21
DP  - 1999 May 21
TI  - The heparin-binding domain of extracellular superoxide dismutase is
      proteolytically processed intracellularly during biosynthesis.
PG  - 14818-22
AB  - Extracellular superoxide dismutase (EC-SOD) is the only known extracellular
      enzyme designed to scavenge the superoxide anion. The purified enzyme exists in
      two forms when visualized by reduced SDS-polyacrylamide gel electrophoresis: (i) 
      intact EC-SOD (Trp1-Ala222) containing the C-terminal heparin-binding domain and 
      (ii) cleaved EC-SOD (Trp1-Glu209) without the C-terminal heparin-binding domain. 
      The proteolytic event(s) leading to proteolysis at Glu209-Arg210 and removal of
      the heparin-binding domain are not known, but may represent an important
      regulatory mechanism. Removal of the heparin-binding domain affects both the
      affinity of EC-SOD for and its distribution to the extracellular matrix, in which
      it is secreted. During the purification of human EC-SOD, the intact/cleaved ratio
      remains constant, suggesting that proteolytic removal of the heparin-binding
      domain does not occur during purification (Oury, T. D., Crapo, J. D., Valnickova,
      Z., and Enghild, J. J. (1996) Biochem. J. 317, 51-57). This was supported by the 
      finding that fresh mouse tissue contains both intact and cleaved EC-SOD. To study
      other possible mechanisms leading to the formation of cleaved EC-SOD, we examined
      biosynthesis in cultured rat L2 epithelial-like cells using a pulse-chase
      protocol. The results of these studies suggest that the heparin-binding domain is
      removed intracellularly just prior to secretion. In addition, the intact/cleaved 
      EC-SOD ratio appears to be tissue-dependent, implying that the intracellular
      processing event is regulated in a tissue-specific manner. The existence of this 
      intracellular processing pathway may thus represent a novel regulatory pathway
      for affecting the distribution and effect of EC-SOD.
FAU - Enghild, J J
AU  - Enghild JJ
AD  - Department of Pathology, Duke University Medical Center, Durham, North Carolina
      27710, USA. enghi001@mc.duke.edu
FAU - Thogersen, I B
AU  - Thogersen IB
FAU - Oury, T D
AU  - Oury TD
FAU - Valnickova, Z
AU  - Valnickova Z
FAU - Hojrup, P
AU  - Hojrup P
FAU - Crapo, J D
AU  - Crapo JD
LA  - eng
GR  - HL31992/HL/NHLBI NIH HHS/United States
GR  - HL42444/HL/NHLBI NIH HHS/United States
GR  - HL49542/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 9005-49-6 (Heparin)
RN  - EC 1.15.1.1 (Superoxide Dismutase)
SB  - IM
MH  - Animals
MH  - Culture Techniques
MH  - Extracellular Space/metabolism
MH  - Heparin/*pharmacokinetics
MH  - Humans
MH  - Mice
MH  - *Protein Splicing
MH  - Rats
MH  - Superoxide Dismutase/*biosynthesis/*metabolism
EDAT- 1999/05/18 00:00
MHDA- 1999/05/18 00:01
CRDT- 1999/05/18 00:00
PHST- 1999/05/18 00:00 [pubmed]
PHST- 1999/05/18 00:01 [medline]
PHST- 1999/05/18 00:00 [entrez]
AID - 10.1074/jbc.274.21.14818 [doi]
PST - ppublish
SO  - J Biol Chem. 1999 May 21;274(21):14818-22. doi: 10.1074/jbc.274.21.14818.