Disease relevance of Tnnt2

• Staining for cTnT decreased simultaneously with increases in the severity of the cardiomyopathy scores [1].
• Thus, monitoring serum levels of cTnT can detect doxorubicin-induced myocyte damage in SHR and may prove useful for the noninvasive evaluation of this toxicity in humans [2].
• No arrhythmia was observed in human wt cTnT expressors [3].
• By contrast, human cTnT wild-type animals reveal a gain of function and cardiac hypertrophy without arrhythmias [3].
• In contrast, human wt cTnT hearts showed improved contractile performance and moderate myocardial hypertrophy [3].

High impact information on Tnnt2

• Restriction-digest analysis of genomic DNA has indicated that the rabbit cTnT gene is a single-copy gene. cTnT cDNA clones were isolated from cDNA libraries, yielding a consensus sequence for the protein [4].
• CONCLUSION: cTnT is released from doxorubicin-damaged myocytes [1].
• RESULTS: Increases in serum levels of cTnT (0.03 to 0.05 ng/mL) and myocardial lesions (cardiomyopathy scores of 1 or 1.5) were found in one out of five and two out of five SHR given 2 and 4 mg/kg doxorubicin, respectively [1].
• However, the alternative splicing patterns of canine cTnT are different in developing cardiac and skeletal muscles, suggesting abnormality of trans-regulatory factors [5].
• Adult cardiac muscle normally expresses a single cardiac troponin T (cTnT) [5].

Chemical compound and disease context of Tnnt2

• This study was aimed to evaluate the preventive role of naringin on cardiac troponin T (cTnT), lactate dehydrogenase (LDH)-isoenzyme, cardiac marker enzymes, electrocardiographic (ECG)-patterns and lysosomal enzymes in isoproterenol (ISO)-induced myocardial infarction (MI) in male Wistar rats [6].

Biological context of Tnnt2

• By using DNA affinity purification, DNA-binding proteins with apparent molecular masses of 22-26 kDa were identified from rat heart extract but not from skeletal and liver extracts, suggesting the involvement of cardiac-specific proteins in regulating the cTnT gene expression [7].
• To investigate the causal relationship of cTnT mutations and this particular phenotype, we sought to establish a transgenic rat model for the disease [3].
• Transgenic rat hearts were characterized by histology, immunohistochemistry and in the 'working heart'. RESULTS: Human wild-type and del ex16 cTnT were stably expressed and incorporated into the sarcomere of transgenic cardiomyocytes [3].
• Cardiac troponin T (cTnT) is an established marker of myocyte damage, and a rat transplantation model of heart transplant rejection has suggested that cTnT may be of value in detecting rejection [8].
• Correlations between maximal cTnI and cTnT and AUC were 0.69 (P=0.0001) and 0.60 (P=0.0066), respectively [9].

Anatomical context of Tnnt2

• Our observation demonstrates that qualitative changes in MHC isoform alters the nature of cardiac myofilament dysfunction induced by mutations in cTnT [10].
• At the end of the second day, blood samples were taken from the abdominal aorta shortly after the rats were anesthetized for the purpose of measuring cardiac troponins T (cTnT) and I (cTnI); hearts were removed, preserved and examined microscopically [11].
• Whereas the cytomegalovirus (CMV) promoter yielded high levels of protein expression in all cells studied, cardiac troponin T (cTnT) promoter segments demonstrated high specificity for cardiac myocytes [12].
• Tissue homogenates of the left ventricle were analyzed by Western blot analysis for cardiac troponin T (cTnT) [13].
• Conventional and confocal microscopy of transfected cells, double-labelled with antibodies against cTnT and against TM, revealed that neither isoform appears to associate with the nonmuscle TM in CHO cells, although both are able to colocalize with muscle TM-containing microfilament bundles in the myogenic CEM cells [14].

Associations of Tnnt2 with chemical compounds

• All animals given 6 mg/kg or more of doxorubicin had increases in serum cTnT and myocardial lesions [1].
• Such differences in tension cost were substantiated by the mechano-dynamic analysis of cTnT mutant reconstituted muscle fibres from normal and PTU-treated rat hearts [10].
• Haemodynamic parameters were continuously recorded and at the end of the experiments infarct size (with p-nitro-blue tetrazolium) and cTnT release were determined [15].
• The cTnT loss could not be prevented by using polystyrene or siliconized glass, but was partially inhibited in effluent with albumin [16].
• Pretreatment with naringin (10, 20 or 40mg/kg) daily for a period of 56 days positively altered the levels of cTnT, intensity of the bands of the LDH1 and LDH2-isoenzyme and the activities of cardiac marker enzymes, ECG-patterns and lysosomal hydrolases in ISO-induced rats [6].

Analytical, diagnostic and therapeutic context of Tnnt2

• RT-PCR in the 3' half of the cDNAs confirmed an additional region of heterogeneity: the presence, in part or in full, or absence of a 9-nt region, which matches the alternatively spliced exon 12 described for rat cTnT [4].
• Cardiomyopathy scores were assessed according to the method of Billingham and serum levels of cTnT were quantified by a noncompetitive immunoassay [1].
• Myocardial localization of cTnT was studied by immunohistochemical staining and confocal microscopy [1].
• METHODS: Skeletal muscles (gastrocnemius) were collected from both five-sixths nephrectomized rats (n = 11) and sham-operated controls (n = 11). cTnT content was analyzed by Elecsys (Roche), immunoblotting, and immunohistochemistry with antibodies M7 and M11-7 (Roche) [17].
• Elevation of cTnT after transplantation does not seem to be directly related to ischemic time [8].

References