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Effects of Resveratrol on diabetes‐induced up‐regulation of apoptosis and MAPK signaling in retinal pigment epithelium of dark Agouti rats
Author(s) -
Kittaneh Rawan,
AlHussaini Heba,
Narayana Kilarkaje
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.lb140
Subject(s) - resveratrol , diabetes mellitus , streptozotocin , apoptosis , mapk/erk pathway , cytochrome c , medicine , endocrinology , caspase 3 , kinase , chemistry , biology , pharmacology , microbiology and biotechnology , biochemistry , programmed cell death
Although diabetic retinopathy (DRT) is a treacherous outcome of uncontrolled hyperglycemia, the mechanisms which initiate the onset of DRT are not yet clear. The current study investigated modulatory effects of Resveratrol on type 1 diabetes‐induced changes in apoptosis and mitogen‐activated protein kinase (MAPK) signaling in retinal pigmented epithelium (RPE) of dark Agouti rats. Adult male rats (12–14 weeks, n=15) were segregated in duplicates into normal control, Resveratrol‐treated, streptozotocin‐induced diabetic, and Resveratrol‐treated (5mg/kg/d, from the day of confirmation of diabetes to the sample collection day) diabetic groups. The RPE was collected on days 30 and 90. For the latter sampling time, another Resveratrol‐treated (from 45d after the confirmation of diabetes to sampling day 90) diabetic group was included to investigate the effects of different treating protocol of Resveratrol. Resveratrol when administered to normal rats, increased gene expressions (RT‐PCR analysis) of caspases‐3 , 8 and 9 , Bax , Bcl2 , p38MAPK , JNK , and p53 on 30d (P<0.05). On the other hand, diabetes decreased gene expressions of caspase‐3 and 8 , Erk , p38MAPK , and JNK (P<0.05). Resveratrol reversed the inhibited gene expressions of caspase‐8 , Erk , JNK and p38MAPK to normal control levels in diabetic rats (P<0.05). Resveratrol normalized diabetes‐induced upregulation of proteins (Western blotting analysis) caspase‐3 and 9, cytochrome‐c, Bcl2 and ERK (P<0.05) on 30d. On 90d, Resveratrol recovered diabetes‐induced decreases in caspases‐3 and 8 (18 kDa fragment), cytochrome‐c, and Bcl2 proteins to the control level. Similar effects of Resveratrol were observed when given to diabetic rats only for 45d instead of 90d. In conclusion, Resveratrol when given to normal rats upregulates transcription of apoptosis and MAPK genes, however, their protein levels do not increase suggesting the lack of induction of apoptosis and MAPK‐mediated cell signaling. Resveratrol imparts its protective effects by normalizing apoptosis and MAPK signaling. These results are suggestive of beneficial effects of Resveratrol on the RPE in diabetic rats. Support or Funding Information College of Graduate studies and Research sector, Kuwait University This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .