[Expressions of PDCD5 and other apoptosis-related proteins in muscle of patients with mitochondrial cytopathy].
OBJECTIVE
To investigate the expression of PDCDS, Caspase-3, Bcl-2 and Bax in skeletal muscle of patients with mitochondrial encephalomyopathies with lactate acidosis and stroke like episodes (MELAS), limb-girdle type mitochondrial myopathy (LGMM) and chronic progressive external ophthalmoplegia (CPEO), and to explore the correlation between apoptosis and the pathogenesis of mitochondrial cytopathy.


METHODS
Three patients with MELAS, 2 patients with LGMM and 6 patients with CPEO were enrolled, including eight males and three females, the diagnosis of MELAS, LGMM or CPEO was made on the basis of clinical manifestations, muscle biopsy specimen findings and a point mutation or a large-scale mitochondrial DNA deletion. Controls consisted of 11 muscle biopsy samples from subjects with no diagnostic findings (age and gender matched with patients'). Muscle biopsy was performed after obtaining the informed consent. The specimens were quickly frozen and transverse sections stained for hematoxylineosin, periodic acid Schiff reaction, oil red "0", modified Gomori trichrome, ATPase, NADH-TR, succinate dehydrogenase, cytochrome c oxidase, and nonspecific esterase. The expression of PDCD5, Caspase-3, Bcl-2 and Bax were detected by immunohistochemistry. The authors used the tissue slices of prostate or tonsil containing the target protein as positive control and PBS in place of these primary antibodies as negative control.


RESULTS
PDCDS was highly expressed in some ragged red fibers in 2 patients with LGMM and 3 patients with CPEO. And it was also expressed in some capillary of patients with MELAS and LGMM. Caspase-3 was expressed in a few ragged red fibers in 1 patients with MELAS, 2 patients with LGMM and 1 patient with CPEO. And there was also expression in some capillary of both MELAS and LGMM. Bcl-2 staining showed a high expression in sarcoplasm of some ragged red fibers and atrophic fibers in 4 patients with MELAS, 2 patients with LGMM and 5 patients with CPEO, at the same time, it was weakly expressed in sarcoplasm of all type 2 muscle fibers and some small vessels of both patients and controls. There was no Bax immunoreactive fiber or vessel in MELAS, LGMM and CPEO patients. All of the above-mentioned proteins except Bcl-2 were negative in muscle fibers and vessels of controls.


CONCLUSIONS
Abnormal regulation of apoptosis is involved in the pathophysiology of mitochondrial cytopathy. And PDCDS, Bcl-2 and Caspase-3 take part in regulation.
Li
Yong-fie
YF
Department of Neurology, First Hospital, Peking University, Beijing, China.
Wang
Zhao-xia
ZX
Gao
Xu-guang
XG
Hong
Dao-jun
DJ
Yuan
Yun
Y
D000293:Adolescent; D000328:Adult; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D053148:Caspase 3 / Q000378:metabolism; D005260:Female; D006801:Humans; D017241:MELAS Syndrome / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D028361:Mitochondrial Diseases / Q000378:metabolism* / Q000473:pathology*; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology; D009363:Neoplasm Proteins / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D055815:Young Adult; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D051017:Apoptosis Regulatory Proteins; C494826:BAX protein, human; D009363:Neoplasm Proteins; C117283:PDCD5 protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D053148:Caspase 3