Fas, Caspase‐8, and Caspase‐9 pathway‐mediated bile acid‐induced fetal cardiomyocyte apoptosis in intrahepatic cholestasis pregnant rat models

ABSTRACT A previous study demonstrated that infection of rat oligodendrocytes by mouse hepatitis virus (MHV) resulted in apoptosis, which is caspase dependent (Y. Liu, Y. Cai, and X. Zhang, J. Virol. 77:11952-11963, 2003). Here we determined the involvement of the mitochondrial pathway in MHV-induced oligodendrocyte apoptosis. We found that caspase-9 activity was 12-fold higher in virus-infected cells than in mock-infected cells at 24 h postinfection (p.i.). Pretreatment of cells with a caspase-9 inhibitor completely blocked caspase-9 activation and partially inhibited the apoptosis mediated by MHV infection. Analyses of cytochrome c release further revealed an activation of the mitochondrial apoptotic pathway. Stable overexpression of the two antiapoptotic proteins Bcl-2 and Bcl-xL significantly, though only partially, blocked apoptosis, suggesting that activation of the mitochondrial pathway is partially responsible for the apoptosis. To identify upstream signals, we determined caspase-8 activity, cleavage of Bid, and expression of Bax and Bad by Western blotting. We found a drastic increase in caspase-8 activity and cleavage of Bid at 24 h p.i. in virus-infected cells, suggesting that Bid may serve as a messenger to relay the signals from caspase-8 to mitochondria. However, treatment with a caspase-8 inhibitor only slightly blocked cytochrome c release from the mitochondria. Furthermore, we found that Bax but not Bad was significantly increased at 12 h p.i. in cells infected with both live and UV-inactivated viruses and that Bax activation was partially blocked by treatment with the caspase-8 inhibitor. These results thus establish the involvement of the mitochondrial pathway in MHV-induced oligodendrocyte apoptosis.

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Coronary Microembolization Induces Cardiomyocyte Apoptosis in Swine by Activating the LOX-1-Dependent Mitochondrial Pathway and Caspase-8-Dependent Pathway

Journal of Cardiovascular Pharmacology and Therapeutics ◽

10.1177/1074248415599265 ◽

2015 ◽

Vol 21 (2) ◽

pp. 209-218 ◽

Cited By ~ 9

Author(s):

Tao Liu ◽

You Zhou ◽

Jiang-You Wang ◽

Qiang Su ◽

Zhong-Li Tang ◽

...

Keyword(s):

Mitochondrial Pathway ◽

Cardiomyocyte Apoptosis ◽

Caspase 8 ◽

Coronary Microembolization ◽

Dependent Pathway

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Intrahepatic cholestasis of pregnancy: maternal and fetal outcome and its correlation with serum bile acid levels

International Journal of Reproduction Contraception Obstetrics and Gynecology ◽

10.18203/2320-1770.ijrcog20184480 ◽

2018 ◽

Vol 7 (11) ◽

pp. 4403

Author(s):

Bhawna Sharma ◽

Neetu Arora ◽

Kusum Dogra ◽

Kamal S. Negi

Keyword(s):

Bile Acid ◽

Cesarean Delivery ◽

Intrahepatic Cholestasis ◽

Perinatal Death ◽

Tertiary Care ◽

Neonatal Outcomes ◽

Serum Bile Acid ◽

Intrahepatic Cholestasis Of Pregnancy ◽

Vaginal Deliveries ◽

Cholestasis Of Pregnancy

Background: Maternal, fetal, and neonatal outcomes in parturients with intrahepatic cholestasis of pregnancy (ICP) have been retrospectively documented. We aimed to present pregnancy outcomes of parturients with ICP who underwent delivery. The study was conducted during a 1-year period in a tertiary care centre.Methods: Data from 1 January to 31 December 2017 were collected to identify parturients with ICP.Results: Almost 3/4th of births came to a vaginal delivery (76.74%) and only 10 parturients had cesarean delivery. 4 of 10 parturients underwent nonelective cesarean section, while 6 had elective cesarean delivery. 15.15 % vaginal deliveries were instrumental. The most common indications for emergency LSCS and instrumental deliveries was fetal distress followed by failure to progress of labour. Most births occurred at or after 37 weeks of gestation (65%). Regarding neonatal outcomes in terms of birth weight and Apgar scores at 1 and 5 min, they were positive, as well. None of the babies had Apgar score < 7 at 5 minutes. No case of perinatal death was observed.Conclusions: Although the results were generally positive, larger studies need to be conducted to evaluate the maternal and fetal outcomes in ICP and correlation with serum bile acid levels.

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Inclusion Complex of Zerumbone with Hydroxypropyl-β-Cyclodextrin Induces Apoptosis in Liver Hepatocellular HepG2 Cells via Caspase 8/BID Cleavage Switch and Modulating Bcl2/Bax Ratio

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2013/810632 ◽

2013 ◽

Vol 2013 ◽

pp. 1-16 ◽

Cited By ~ 13

Author(s):

Nabilah Muhammad Nadzri ◽

Ahmad Bustamam Abdul ◽

Mohd Aspollah Sukari ◽

Siddig Ibrahim Abdelwahab ◽

Eltayeb E. M. Eid ◽

...

Keyword(s):

Inclusion Complex ◽

Mitochondrial Membrane ◽

Morphological Study ◽

Caspase 3 ◽

Anticancer Agent ◽

Caspase 8 ◽

Caspase 9 ◽

Solubility In Water ◽

Anticancer Effects ◽

First Time

Zerumbone (ZER) isolated fromZingiber zerumbetwas previously encapsulated with hydroxypropyl-β-cyclodextrin (HPβCD) to enhance ZER’s solubility in water, thus making it highly tolerable in the human body. The anticancer effects of this new ZER-HPβCD inclusion complex via apoptosis cell death were assessed in this study for the first time in liver hepatocellular cells, HepG2. Apoptosis was ascertained by morphological study, nuclear stain, and sub-G1 cell population accumulation with G2/M arrest. Further investigations showed the release of cytochrome c and loss of mitochondrial membrane potential, proving mitochondrial dysfunction upon the ZER-HPβCD treatment as well as modulating proapoptotic and anti-apototic Bcl-2 family members. A significant increase in caspase 3/7, caspase 9, and caspase 8 was detected with the depletion of BID cleaved by caspase 8. Collectively, these results prove that a highly soluble inclusion complex of ZER-HPβCD could be a promising anticancer agent for the treatment of hepatocellular carcinoma in humans.

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