ER Stress Drives Lipogenesis and Steatohepatitis via Caspase-2 Activat…

  • Hit 668
  • Writer 최고관리자
  • 2018-05-25



▶Subject: ER Stress Drives Lipogenesis and Steatohepatitis via Caspase-2 Activation of S1P

▶Speaker: Kim, Ju Youn, Ph.D.

▶Date: 4:00 PM/May. 28(Mon.)/2018

▶Place: Life Science Bldg. #104

Nonalcoholic fatty liver disease (NAFLD) progresses to  nonalcoholic steatohepatitis (NASH) in response to elevated endoplasmic reticulum (ER) stress. Whereas the onset of  simple  steatosis  requires  elevated  de  novo  lipogenesis,  progression  to  NASH  is triggered by accumulation of hepatocyte free cholesterol. We now show that caspase-2, whose  expression  is  ER-stress-inducible  and  elevated  in  human  and  mouse  NASH, controls  the  buildup  of  hepatic  free  cholesterol  and  triglycerides  by  activating  sterol regulatory  element  binding  proteins  (SREBP)  in  a  manner  refractory  to  feedback inhibition. Caspase-2 colocalizes with site 1 protease (S1P) and cleaves it to generate a soluble active fragment that initiates SCAP-independent SREBP1/2 activation in the ER. Caspase-2  ablation  or  pharmacological  inhibition  prevents  diet-induced  steatosis  and NASH  progression  in  ER-stress-prone  mice.  Caspase-2  inhibition  offers  a  specific  and effective  strategy  for  preventing  or  treating  stress-driven  fatty  liver  diseases,  whereas caspase-2-generated S1P proteolytic fragments, which enter the secretory pathway, are potential NASH biomarkers.

▶Inquiry: Prof. Seung Tae Baek(279-2360)

* This seminar will be given in English.
Please refrain from taking photos during seminars. *