Kearns‐sayre syndrome: Biochemical studies of mitochondrial metabolism

Martens, Margaret E.; Peterson, Pamela E.; Lee, C. P.; Nigro, Michael A.; Hart, Zwi H.; Glasberg, Mark R.; Hatfield, James S.; Chang, Chung Ho

doi:10.1002/ana.410240507

Cited by 23 publications

(8 citation statements)

References 26 publications

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“…Clearly the deletion of mitochondrial DNA in KSS has a major effect on many organ systems. Mitochondria1 oxidative phosphorylation is impaired (Martens et al, 1988). Measurements of intermediary metabolites such as lactate, pyruvate and alanine indicate this is a general feature of mitochondrial disease.…”

Section: Discussionmentioning

confidence: 99%

Endocrine dysfunction in Kearns‐Sayre syndrome

Harvey

Barnett

1992

Clinical Endocrinology

150

100

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Kearns-Sayre syndrome (KSS) is a form of mitochondrial myopathy in which specific clinical features, namely progressive external ophthalmoplegia, pigmentary retinal degeneration and cardiac conduction defects, occur. KSS has also been associated with a variety of endocrine and metabolic disorders, in particular short stature, gonadal failure, diabetes mellitus, thyroid disease, hyperaldosteronism, hypomagnesaemia, and bone, tooth and calcification abnormalities. A case is described exhibiting all of these features. A survey of the literature was conducted to determine the prevalence of these conditions among reported cases. Cases with hypoparathyroidism were considered separately to see if they constituted a distinct subgroup with multiple endocrine dysfunction. Short stature was common, being documented in 38% of cases. Gonadal dysfunction before or after puberty was also common (20% of cases) and affected both sexes equally. Diabetes mellitus was recorded in 13% of cases, half of which required insulin. Thyroid disease, hyperaldosteronism and hypomagnesaemia were uncommon but were probably not looked for in many cases. Bone or tooth abnormalities and calcification of the basal ganglia were found both in those with and without hypoparathyroidism. While endocrine and metabolic dysfunction was found more commonly in those with hypoparathyroidism this is likely to be due to increased recognition rather than increased prevalence. No evidence of an autoimmune polyendocrine syndrome including hypoparathyroidism was found.

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Section: Discussionmentioning

confidence: 99%

Endocrine dysfunction in Kearns‐Sayre syndrome

Harvey

Barnett

1992

Clinical Endocrinology

150

100

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“…Routine diagnostic studies included standard histological and histochemical staining of frozen sections and polarographic analysis of oxygen consumption by isolated mitochondria (patients 3 and 4) (12). Frozen autopsy specimens were obtained from a 13-year-old girl with chronic external ophthalmoplegia and cardiac dysfunction, studied clinically and biochemically at the Wayne State University School of Medicine (13). All studies were approved by the Joint Committee on Clinical Investigation of the Johns Hopkins Medical Institutions and those of the referring institutions.…”

Section: Methodsmentioning

confidence: 99%

Directly repeated sequences associated with pathogenic mitochondrial DNA deletions.

Johns

Rutledge

Stine³

et al. 1989

Proc. Natl. Acad. Sci. U.S.A.

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“…The respiratory control ratio and phosphate to oxygen ratio number of these preparations were 4.7 and 2.1, respectively, assayed in the presence of 10 mM succinate and 0.45 mM ADP in reaction buffer (0.225 M sucrose, 10 mM potassium phosphate, 5 mM MgCl 2 , 20 mM Hepes, pH 7.4). The absorption spectra were recorded using an SLM-Aminco DW-2C UV-visible spectrophotometer as described previously (33). The difference spectra of samples, which contained 1 mg of mitochondrial protein in reaction buffer, were recorded under the following conditions: 20 …”

Section: Role Of S-nitrosoglutathione Metabolism In the Hydrogenmentioning

confidence: 99%

The Modulation of Oxygen Radical Production by Nitric Oxide in Mitochondria

Sarkela

Berthiaume²,

Elfering³

et al. 2001

Journal of Biological Chemistry

107

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Biological systems that produce or are exposed to nitric oxide (NO ⅐ ) exhibit changes in the rate of oxygen free radical production. Considering that mitochondria are the main intracellular source of oxygen radicals, and based on the recently documented production of NO ⅐ by intact mitochondria, we investigated whether NO ⅐ , produced by the mitochondrial nitric-oxide synthase, could affect the generation of oxygen radicals. Toward this end, changes in H 2 O 2 production by rat liver mitochondria were monitored at different rates of endogenous NO ⅐ production. The observed changes in H 2 O 2 production indicated that NO ⅐ affected the rate of oxygen radical production by modulating the rate of O 2 consumption at the cytochrome oxidase level. This mechanism was supported by these three experimental proofs: 1) the reciprocal correlation between H 2 O 2 production and respiratory rates under different conditions of NO ⅐ production; 2) the pattern of oxidized/reduced carriers in the presence of NO ⅐ , which pointed to cytochrome oxidase as the crossover point; and 3) the reversibility of these effects, evidenced in the presence of oxymyoglobin, which excluded a significant role for other NO ⅐ -derived species such as peroxynitrite. Other sources of H 2 O 2 investigated, such as the aerobic formation of nitrosoglutathione and the GSH-mediated decay of nitrosoglutathione, were found quantitatively negligible compared with the total rate of H 2 O 2 production.Biological systems of diverse complexity, when exposed to NO ⅐ 1 or stimulated to produce NO ⅐ , usually present changes in the rate of oxygen free radical production (Ref. 1 and references therein). Decreases in the rate of oxygen free radical production are often attributed to the diffusion-controlled reaction between O 2 . and NO ⅐ , which yields peroxynitrite. Increases in reactive oxygen species (ROS) production are usually associated with the damage and/or inactivation of mitochondrial components by peroxynitrite or peroxynitrite-like species.Considering that under physiological conditions mitochondria constitute the main intracellular source of oxygen free radicals (2, 3) and that these organelles can produce NO ⅐ (4 -8), it becomes of interest to examine whether the production of mitochondrial ROS is affected by endogenous NO ⅐ . The accurate documentation of the rates of production of nitrogen and oxygen radicals is an essential step to understanding the role of these interactions in different, more complex pathophysiological situations and underlines the relevance of studying the mechanisms behind these processes in relatively simpler models. Furthermore, transient changes in ROS production have become an area of intense research given the growing interest in the role of ROS as mediators of signal transduction pathways, organ preconditioning (9), and apoptotic processes (10).In this study, we examined the rates of O 2 free radical production by intact mitochondria under various conditions of endogenous NO ⅐ production; different mechanisms underlying th...

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Kearns‐sayre syndrome: Biochemical studies of mitochondrial metabolism

Cited by 23 publications

References 26 publications

Endocrine dysfunction in Kearns‐Sayre syndrome

Endocrine dysfunction in Kearns‐Sayre syndrome

Directly repeated sequences associated with pathogenic mitochondrial DNA deletions.

The Modulation of Oxygen Radical Production by Nitric Oxide in Mitochondria

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