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林威佑、戴槐青、鄭劍廷 1 、余宏政

Activating Nrf-2 Signaling by Sulforaphane Attenuates Unilateral Ureteral Obstruction-Enhanced Apoptosis and Pyroptosis in Kidney. 林威佑、戴槐青、鄭劍廷 1 、余宏政. 台灣大學醫學院附設醫院 泌尿部 1 國立臺灣師範大學生命科學系. Introduction. Clinically, ureteral obstruction is a common problem. Incidence: 3.9% Cause: Ureteral stone

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林威佑、戴槐青、鄭劍廷 1 、余宏政

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  1. Activating Nrf-2 Signaling by Sulforaphane Attenuates Unilateral Ureteral Obstruction-Enhanced Apoptosis and Pyroptosis in Kidney 林威佑、戴槐青、鄭劍廷1、余宏政 台灣大學醫學院附設醫院 泌尿部 1國立臺灣師範大學生命科學系

  2. Introduction • Clinically, ureteral obstruction is a common problem. • Incidence: 3.9% • Cause: • Ureteral stone • Benign prostate hyperplasia • Urothelial tumor • Other causes such as ureteral stricture Hegarty et al., 2001

  3. Increased reactive oxygen species (ROS) may promote two types of programmed cell death in the obstructed kidney • apoptosis and pyroptosis • Sulforaphane (SA) via activating Nrf-2 antioxidant signaling may protect UUO-induced renal damage

  4. Method • Unilateral ureteral obstruction (UUO) • A well animal model of mimic renal injury leading to interstitial fibrosis Nagatoya et al., 2002 • Left kidney of Female Wistar rats • Normal • UUO • UUO and sulforaphane

  5. Reactive oxygen species (ROS) • Fibrosis, ED-1 (macrophage/monocyte) infiltration, oxidative stress, autophagy, apoptosis and pyroptosis Immunohistochemisty and Western blot

  6. Result

  7. H.E.Stain Normal UUO 7day SA UUO 7day ED1 Stain Macrophage Normal UUO 7day SA UUO 7day

  8. 4HNE Stain Lipid Oxide Normal UUO 7day SA UUO7day

  9. Beclin Stain Autophagy Normal UUO 7day UUO & SA 7day Beclin 1 Normal β-actin UUO 7day SA UUO 7day 偵測腎臟組織細胞自噬初期蛋白Beclin-1表現，觀察時間點為Normal、阻塞七天、阻塞七天+DL-蘿蔔硫素(n=3)。 ＊表示與Normal組有顯著差異(p<0.05)。

  10. N Engl J Med 2012

  11. ATG5-ATG12 Stain Autophagy Normal UUO 7day UUO & SA 7day Atg5-Atg12 Normal β-actin UUO 7day SA UUO 7day 偵測腎臟組織細胞自噬過程促自噬泡形成之Atg5-Atg12蛋白表現，觀察時間點為Normal、阻塞七天、阻塞七天+ DL-蘿蔔硫素(n=3)。 ＊表示與Normal組有顯著差異(p<0.05)。

  12. N Engl J Med 2012

  13. LC3II Stain Autophagy Normal UUO 7day UUO & SA 7day LC3II Normal β-actin UUO 7day SA UUO 7day 偵測腎臟組織細胞自噬之自噬泡形成代表性蛋白LC3 typeⅡ表現，觀察時間點為Normal、阻塞七天、阻塞七天+ DL-蘿蔔硫素(n=3)。 ＊表示與Normal組有顯著差異(p<0.05)。

  14. N Engl J Med 2012

  15. IL1-βStain pyropotosis Caspase1 Stain pyropotosis Normal Normal UUO 7day UUO 7day SA UUO 7day SA UUO 7day

  16. Nrf2 Stain Normal UUO 7day UUO & SA 7day Nrf2 Normal β-actin UUO 7day SA UUO 7day 偵測腎臟組織細胞自噬過程Nrf2蛋白表現，觀察時間點為Normal、阻塞七天、阻塞七天+ DL-蘿蔔硫素(n=3)。 ＊表示與control組有顯著差異(p<0.05)。

  17. UOO sulforaphane Cytosolic Nrf-2 Nuclear Nrf-2 translocation Cytosolic Bax translocation to mitochondria MOMP Enhance mitochondrial Cytochrome c release into the cytosol

  18. Cytochrome C Stain Control UUO 7day SA UUO7day

  19. Masson Stain Hydroxylproline Normal UUO 7day SA UUO7day

  20. Conclusion • Conclusion: Sulforaphane via activating Nrf-2 signaling to preserve mitochondrial function and suppressed UUO-induced renal apoptosis and pyroptosis

  21. Thank you for your attention!!

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