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Minocycline inhibits PARP‑1 expression and decreases apoptosis in diabetic retinopathy.

Wu Y, Chen Y, Wu Q, Jia L, Du X - Mol Med Rep (2015)

Bottom Line: The present study aimed to investigate the mechanism underlying the effects of minocycline on diabetic retinopathy‑associated cellular apoptosis.Following treatment with minocycline, the abnormal expression of PARP‑1 in the retina was inhibited, and cellular apoptosis was decreased.In conclusion, the results of the present study suggest that PARP‑1 is involved in the development of diabetic retinopathy, and minocycline is able to inhibit PARP‑1 expression and decrease cellular apoptosis, suggesting that minocycline may prove to be a promising drug for the treatment of diabetic retinopathy.

View Article: PubMed Central - PubMed

Affiliation: Department of Ultrasound, Shanghai First People's Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200080, P.R. China.

ABSTRACT
The present study aimed to investigate the mechanism underlying the effects of minocycline on diabetic retinopathy‑associated cellular apoptosis. A total of 40 Sprague Dawley (SD) rats were used as a diabetic retinopathy model following injection with streptozotocin. Among the 34 rats in which the diabetes model was successfully established, 24 rats were divided into two experimental groups: I and II (T1 and T2, respectively), and orally administered with various doses of minocycline. The remaining 10 rats served as the diabetic retinopathy control group. An additional group of 10 healthy SD rats with comparable weight served as normal controls. The rats in T1 and T2 groups were treated daily for eight consecutive weeks with minocycline at a dose of 2.5 mg/kg and 5 mg/kg, respectively. The mRNA expression levels of poly (ADP‑ribose) polymerase‑1 (PARP‑1) were subsequently measured by reverse transcription‑quantitative polymerase chain reaction, and the protein expression levels of poly‑ADP‑ribose were measured by western blot analysis and immunohistochemistry. Retinal morphology was observed following hematoxylin and eosin staining, and retinal cell apoptosis was measured by terminal deoxynucleotidyl transferase dUTP nick end labeling and caspase‑3 activity assays. The amplitudes of the electroretinogram (ERG) b‑wave and oscillary potentials (OPs) were measured using visual electrophysiology, and compared among the four groups. The results of the present study demonstrated that in the diabetic rats, retinal PARP‑1 gene expression was markedly upregulated, the number of apoptotic cells and the activity levels of caspase‑3 were increased, and the amplitude of the ERG b‑wave and the OPs were markedly lower as compared with the normal rats. Following treatment with minocycline, the abnormal expression of PARP‑1 in the retina was inhibited, and cellular apoptosis was decreased. In conclusion, the results of the present study suggest that PARP‑1 is involved in the development of diabetic retinopathy, and minocycline is able to inhibit PARP‑1 expression and decrease cellular apoptosis, suggesting that minocycline may prove to be a promising drug for the treatment of diabetic retinopathy.

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The activity levels of caspase-3 in the retinal tissue samples of the CON, DM, T1 and T2 groups. The activity levels of caspase-3 were significantly elevated in the retinal tissue samples of the DM rats, as compared with the CON group. Following minocycline treatment, the elevated activity levels of caspase-3 in the retinal tissue samples of the DM rats was suppressed (F=27.24; *P<0.01 vs. CON and **P<0.01 vs. DM). No statistically significant difference in the activity levels of caspase-3 was observed between the T1 and T2 treatment groups (P>0.05) CON, normal control group; DM, diabetic retinopathy group; T1, 2.5 mg/kg minocycline treatment group; T2, 5 mg/kg minocycline treatment group.
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f4-mmr-12-04-4887: The activity levels of caspase-3 in the retinal tissue samples of the CON, DM, T1 and T2 groups. The activity levels of caspase-3 were significantly elevated in the retinal tissue samples of the DM rats, as compared with the CON group. Following minocycline treatment, the elevated activity levels of caspase-3 in the retinal tissue samples of the DM rats was suppressed (F=27.24; *P<0.01 vs. CON and **P<0.01 vs. DM). No statistically significant difference in the activity levels of caspase-3 was observed between the T1 and T2 treatment groups (P>0.05) CON, normal control group; DM, diabetic retinopathy group; T1, 2.5 mg/kg minocycline treatment group; T2, 5 mg/kg minocycline treatment group.

Mentions: The b-wave amplitudes of the CON group, DM group, and T1 and T2 treatment groups were 255.7±32.79, 148.3±32.62, 161.1±31.47, and 197.1±33.19 µV, respectively (Fig. 4 and 5). The differences between all of the groups were statistically significant (F=32.52, P<0.0001). The b-wave amplitude in the DM group was significantly lower, as compared with the CON, T1 and T2 groups. The b-wave amplitude and OPs in the T1 and T2 treatment groups were lower than in the CON group, but no statistically significant difference was observed between the T1 and T2 groups. The b-wave amplitude in the CON, DM, and T1 and T2 groups was 125.9±19.47, 76.5±16.72, 97.8±15.82, and 101.0±10.45 µV, respectively. Statistically significant differences were present among all four groups. The OP amplitudes in the DM group were significantly lower than in the CON group (F=10.46, P=0.0011). Following treatment with minocycline, the OP amplitude in the T1 and T2 groups was significantly higher as compared with the DM group (P<0.01), and lower as compared with the CON group (P<0.05). The differences in OPs between the T1 and T2 groups was not statistically significant (P>0.05).


Minocycline inhibits PARP‑1 expression and decreases apoptosis in diabetic retinopathy.

Wu Y, Chen Y, Wu Q, Jia L, Du X - Mol Med Rep (2015)

The activity levels of caspase-3 in the retinal tissue samples of the CON, DM, T1 and T2 groups. The activity levels of caspase-3 were significantly elevated in the retinal tissue samples of the DM rats, as compared with the CON group. Following minocycline treatment, the elevated activity levels of caspase-3 in the retinal tissue samples of the DM rats was suppressed (F=27.24; *P<0.01 vs. CON and **P<0.01 vs. DM). No statistically significant difference in the activity levels of caspase-3 was observed between the T1 and T2 treatment groups (P>0.05) CON, normal control group; DM, diabetic retinopathy group; T1, 2.5 mg/kg minocycline treatment group; T2, 5 mg/kg minocycline treatment group.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4581760&req=5

f4-mmr-12-04-4887: The activity levels of caspase-3 in the retinal tissue samples of the CON, DM, T1 and T2 groups. The activity levels of caspase-3 were significantly elevated in the retinal tissue samples of the DM rats, as compared with the CON group. Following minocycline treatment, the elevated activity levels of caspase-3 in the retinal tissue samples of the DM rats was suppressed (F=27.24; *P<0.01 vs. CON and **P<0.01 vs. DM). No statistically significant difference in the activity levels of caspase-3 was observed between the T1 and T2 treatment groups (P>0.05) CON, normal control group; DM, diabetic retinopathy group; T1, 2.5 mg/kg minocycline treatment group; T2, 5 mg/kg minocycline treatment group.
Mentions: The b-wave amplitudes of the CON group, DM group, and T1 and T2 treatment groups were 255.7±32.79, 148.3±32.62, 161.1±31.47, and 197.1±33.19 µV, respectively (Fig. 4 and 5). The differences between all of the groups were statistically significant (F=32.52, P<0.0001). The b-wave amplitude in the DM group was significantly lower, as compared with the CON, T1 and T2 groups. The b-wave amplitude and OPs in the T1 and T2 treatment groups were lower than in the CON group, but no statistically significant difference was observed between the T1 and T2 groups. The b-wave amplitude in the CON, DM, and T1 and T2 groups was 125.9±19.47, 76.5±16.72, 97.8±15.82, and 101.0±10.45 µV, respectively. Statistically significant differences were present among all four groups. The OP amplitudes in the DM group were significantly lower than in the CON group (F=10.46, P=0.0011). Following treatment with minocycline, the OP amplitude in the T1 and T2 groups was significantly higher as compared with the DM group (P<0.01), and lower as compared with the CON group (P<0.05). The differences in OPs between the T1 and T2 groups was not statistically significant (P>0.05).

Bottom Line: The present study aimed to investigate the mechanism underlying the effects of minocycline on diabetic retinopathy‑associated cellular apoptosis.Following treatment with minocycline, the abnormal expression of PARP‑1 in the retina was inhibited, and cellular apoptosis was decreased.In conclusion, the results of the present study suggest that PARP‑1 is involved in the development of diabetic retinopathy, and minocycline is able to inhibit PARP‑1 expression and decrease cellular apoptosis, suggesting that minocycline may prove to be a promising drug for the treatment of diabetic retinopathy.

View Article: PubMed Central - PubMed

Affiliation: Department of Ultrasound, Shanghai First People's Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200080, P.R. China.

ABSTRACT
The present study aimed to investigate the mechanism underlying the effects of minocycline on diabetic retinopathy‑associated cellular apoptosis. A total of 40 Sprague Dawley (SD) rats were used as a diabetic retinopathy model following injection with streptozotocin. Among the 34 rats in which the diabetes model was successfully established, 24 rats were divided into two experimental groups: I and II (T1 and T2, respectively), and orally administered with various doses of minocycline. The remaining 10 rats served as the diabetic retinopathy control group. An additional group of 10 healthy SD rats with comparable weight served as normal controls. The rats in T1 and T2 groups were treated daily for eight consecutive weeks with minocycline at a dose of 2.5 mg/kg and 5 mg/kg, respectively. The mRNA expression levels of poly (ADP‑ribose) polymerase‑1 (PARP‑1) were subsequently measured by reverse transcription‑quantitative polymerase chain reaction, and the protein expression levels of poly‑ADP‑ribose were measured by western blot analysis and immunohistochemistry. Retinal morphology was observed following hematoxylin and eosin staining, and retinal cell apoptosis was measured by terminal deoxynucleotidyl transferase dUTP nick end labeling and caspase‑3 activity assays. The amplitudes of the electroretinogram (ERG) b‑wave and oscillary potentials (OPs) were measured using visual electrophysiology, and compared among the four groups. The results of the present study demonstrated that in the diabetic rats, retinal PARP‑1 gene expression was markedly upregulated, the number of apoptotic cells and the activity levels of caspase‑3 were increased, and the amplitude of the ERG b‑wave and the OPs were markedly lower as compared with the normal rats. Following treatment with minocycline, the abnormal expression of PARP‑1 in the retina was inhibited, and cellular apoptosis was decreased. In conclusion, the results of the present study suggest that PARP‑1 is involved in the development of diabetic retinopathy, and minocycline is able to inhibit PARP‑1 expression and decrease cellular apoptosis, suggesting that minocycline may prove to be a promising drug for the treatment of diabetic retinopathy.

Show MeSH
Related in: MedlinePlus