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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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Expression levels of PAR proteins in the retinal tissue samples of DM rats were significantly higher, as comapred with the CON group. Following minocycline treatment, the expression levels of the PAR proteins were downregulated in the DM rats, as compared with the DM group. (A and B) Western blot analysis demonstrated a significant increase in the protein expression levels of the PAR proteins of the DM group, as compared with the other three groups, however no significant difference was observed between the CON, T1 and T2 groups (F=39.02). *P<0.01 vs. CON; **P<0.01 vs. DM. (C) PAR expression was observed in the retinal ganglion cell layer, inner nuclear layer, and outer nuclear layer, as determined by immunohistochemistry. The PAR protein staining in the retinal tissue samples of the CON group was weakly positive. (D) Positive PAR expression increased significantly in the DM rats. (E and F) Following minocycline treatment, the expression levels of the PAR proteins were downregulated in the T1 and T2 groups. Scale bars, 50 µm. CON, normal control group; DM, diabetic retinopathy group; T1, 2.5 mg/kg minocycline treatment group; T2, 5 mg/kg minocycline treatment group; PAR, poly (ADP-ribose).
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f2-mmr-12-04-4887: Expression levels of PAR proteins in the retinal tissue samples of DM rats were significantly higher, as comapred with the CON group. Following minocycline treatment, the expression levels of the PAR proteins were downregulated in the DM rats, as compared with the DM group. (A and B) Western blot analysis demonstrated a significant increase in the protein expression levels of the PAR proteins of the DM group, as compared with the other three groups, however no significant difference was observed between the CON, T1 and T2 groups (F=39.02). *P<0.01 vs. CON; **P<0.01 vs. DM. (C) PAR expression was observed in the retinal ganglion cell layer, inner nuclear layer, and outer nuclear layer, as determined by immunohistochemistry. The PAR protein staining in the retinal tissue samples of the CON group was weakly positive. (D) Positive PAR expression increased significantly in the DM rats. (E and F) Following minocycline treatment, the expression levels of the PAR proteins were downregulated in the T1 and T2 groups. Scale bars, 50 µm. CON, normal control group; DM, diabetic retinopathy group; T1, 2.5 mg/kg minocycline treatment group; T2, 5 mg/kg minocycline treatment group; PAR, poly (ADP-ribose).

Mentions: IHC showed that the protein expression levels of PAR in the retinal tissue samples of the DM rats were significantly higher, as compared with the CON group (Fig. 2). Positive PAR protein expression was observed in the retinal GCL) the INL, and the outer nuclear layer. Following treatment with minocycline, the expression levels of the PAR proteins were downregulated in the retinal tissue samples of the DM rats. The results of the western blot analysis demonstrated the presence of statistically significant differences in the expression levels of PAR proteins between the DM group and the other three groups (F=39.02, P<0.01); however no statistically significant difference was observed between the treatment and CON groups.


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)

Expression levels of PAR proteins in the retinal tissue samples of DM rats were significantly higher, as comapred with the CON group. Following minocycline treatment, the expression levels of the PAR proteins were downregulated in the DM rats, as compared with the DM group. (A and B) Western blot analysis demonstrated a significant increase in the protein expression levels of the PAR proteins of the DM group, as compared with the other three groups, however no significant difference was observed between the CON, T1 and T2 groups (F=39.02). *P<0.01 vs. CON; **P<0.01 vs. DM. (C) PAR expression was observed in the retinal ganglion cell layer, inner nuclear layer, and outer nuclear layer, as determined by immunohistochemistry. The PAR protein staining in the retinal tissue samples of the CON group was weakly positive. (D) Positive PAR expression increased significantly in the DM rats. (E and F) Following minocycline treatment, the expression levels of the PAR proteins were downregulated in the T1 and T2 groups. Scale bars, 50 µm. CON, normal control group; DM, diabetic retinopathy group; T1, 2.5 mg/kg minocycline treatment group; T2, 5 mg/kg minocycline treatment group; PAR, poly (ADP-ribose).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f2-mmr-12-04-4887: Expression levels of PAR proteins in the retinal tissue samples of DM rats were significantly higher, as comapred with the CON group. Following minocycline treatment, the expression levels of the PAR proteins were downregulated in the DM rats, as compared with the DM group. (A and B) Western blot analysis demonstrated a significant increase in the protein expression levels of the PAR proteins of the DM group, as compared with the other three groups, however no significant difference was observed between the CON, T1 and T2 groups (F=39.02). *P<0.01 vs. CON; **P<0.01 vs. DM. (C) PAR expression was observed in the retinal ganglion cell layer, inner nuclear layer, and outer nuclear layer, as determined by immunohistochemistry. The PAR protein staining in the retinal tissue samples of the CON group was weakly positive. (D) Positive PAR expression increased significantly in the DM rats. (E and F) Following minocycline treatment, the expression levels of the PAR proteins were downregulated in the T1 and T2 groups. Scale bars, 50 µm. CON, normal control group; DM, diabetic retinopathy group; T1, 2.5 mg/kg minocycline treatment group; T2, 5 mg/kg minocycline treatment group; PAR, poly (ADP-ribose).
Mentions: IHC showed that the protein expression levels of PAR in the retinal tissue samples of the DM rats were significantly higher, as compared with the CON group (Fig. 2). Positive PAR protein expression was observed in the retinal GCL) the INL, and the outer nuclear layer. Following treatment with minocycline, the expression levels of the PAR proteins were downregulated in the retinal tissue samples of the DM rats. The results of the western blot analysis demonstrated the presence of statistically significant differences in the expression levels of PAR proteins between the DM group and the other three groups (F=39.02, P<0.01); however no statistically significant difference was observed between the treatment and CON groups.

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