Red blood cells contain a pathway for the degradation of oxidant-damaged hemoglobin that does not require ATP or ubiquitin.

Full Abstract

It is generally accepted that ATP is required for intracellular protein breakdown. Reticulocytes contain a soluble ATP-dependent pathway for the degradation of highly abnormal proteins and for the elimination of certain proteins during cell maturation. Reticulocytes and erythrocytes also selectively degrade proteins damaged by oxidation. When these cells were exposed to oxidants, such as phenylhydrazine or nitrite, they showed a large increase in protein breakdown. This oxidant-induced proteolysis was not inhibited in cells depleted of ATP. However, ATP depletion did prevent the degradation of pre-existent cell proteins. In reticulocyte extracts, phenylhydrazine-treated hemoglobin is also degraded rapidly by an ATP-independent process, unlike endogenous proteins and many exogenous polypeptides. This lack of an ATP requirement means that the degradation of oxidant-damaged proteins does not require ligation to ubiquitin (even though phenylhydrazine treatment does make hemoglobin a very good substrate for ubiquitin conjugation). In many respects, the pathway for breakdown of oxidant-treated hemoglobin differs from the ATP-dependent process. The latter has a much higher activation energy than the degradation of oxidized proteins. The ATP-dependent process is inhibited by hemin, 3,4-dichloroisocoumarin, diisopropylfluorophosphate and N-ethylmaleimide. The ATP-independent pathway is less sensitive to N-ethylmaleimide, hemin, and 3,4-dichloroisocoumarin and is not affected by diisopropylfluorophosphate. In addition, only the ATP-dependent proteolytic process is inactivated by dilution or incubation at 37 degrees C in the absence of nucleotides. Reticulocytes thus contain multiple soluble systems for degrading proteins and can rapidly hydrolyze certain types of abnormal proteins by either an ATP-independent or ATP-dependent process. Erythrocytes lack the ATP-dependent process present in reticulocytes; however, erythrocytes retain the capacity to degrade oxidant-damaged hemoglobin. These two processes probably are active in the elimination of different types of abnormal proteins.

Author information

Author/s: Fagan, J M (JM); Waxman, L (L); Goldberg, A L (AL);

Journal and publication information

Publication Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.

Journal: The Journal of biological chemistry (J Biol Chem), published in UNITED STATES. (Language: eng)

Reference: 1986-May; vol 261 (issue 13) : pp 5705-13

Dates: Created 1986/05/30; Completed 1986/05/30; Revised 2006/11/15;

PMID: 3009430, status: MEDLINE (last retrieval date: 2/18/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

2,4-Dinitrophenol
Adenosine Triphosphate - blood
Animals
Dinitrophenols - pharmacology
Energy Metabolism
Erythrocytes - drug effects; metabolism
Hematocrit
Hemoglobins - metabolism
Humans

Kinetics
Male
Nitrites - pharmacology
Oxidation-Reduction
Phenylhydrazines - pharmacology
Rabbits
Reticulocytes - drug effects; metabolism
Thermodynamics
Ubiquitins - blood

Associated Chemicals: Dinitrophenols (0) ; Hemoglobins (0) ; Nitrites (0) ; Phenylhydrazines (0) ; Ubiquitins (0) ; phenylhydrazine (100-63-0) ; 2,4-Dinitrophenol (51-28-5) ; Adenosine Triphosphate (56-65-5)

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