Physiology and Biophysics

Seminars

Apr
2
Thu
2020
PBio seminar CANCELED for Lorrie Kirshenbaum
Apr 2 @ 9:30 am – 10:30 am

CANCELED

MOLECULAR REGULATION OF CARDIAC CELL DEATH BY MODULATION OF CYCLOPHILIN D IN DOXORUBCIN CARDIOMOPATHY

Dr. Lorrie A. Kirshenbaum Director, Institute of Cardiovascular Sciences Max Rady College of Medicine, University of Manitoba

Host: Chris Liu

OBJECTIVE To understand the role of Nuclear Factor-κB (NF-κB) in the regulation of mitochondrial permeability transition pore opening (mPTP) and cardiac cell death during doxorubicin cardiotoxicity. METHODS AND RESULTS Cardiac myocytes expressing a kinase defective form of IKKβ (IKKK-M) the principle IKK required for NF-κB activation, displayed impaired NF-κB gene activity. Defects in NF-κB signaling coincided with an increase in mitochondrial permeability transition pore (mPTP) opening and cell death. Interestingly, mPTP opening and cell death observed in the NF-κB defective cardiomyocytes was supressed by inhibition of mPTP modulator CypD, with cyclosporin A (CSA) or by siRNA knock down (CypDsiRNA), suggesting a link between mPTP regulation and NF-κB signaling. Interestingly, we observed a dramatic reduction in NF-κB signaling in cardiac myocytes treated with doxorubicin Dox (18 Hrs), coupled with mitochondrial dysfunction that included impaired calcium signaling, oxidative metabolism and mPTP. Inhibition of CyPD suppressed Dox- induced cell death of cardiac myocytes. Finally restoration of NF-κB signaling in cardiac myocytes treated with Dox by IKKβ, active kinase, suppressed mitochondrial calcium overload, mitochondrial perturbations, respiration and cell death. CONCLUSION The data provides the first evidence that impaired NF-κB signaling predisposes in cardiac myocytes treated with DOX to necrotic cell death through a mechanism that impinges upon mPTP
Apr
9
Thu
2020
PBIO seminar CANCELED for Saskia de Vries
Apr 9 @ 9:30 am – 10:30 am

CANCELED

Saskia de Vries, Ph.D.

Assistant Investigator The Allen Institute

host: Adrienne Fairhall

Apr
16
Thu
2020
CANCELED – Barbara Ehrlich 2020 Hille Lecture @ T - 625, HSB
Apr 16 @ 4:00 pm – 5:00 pm

CANCELED

Barbara Ehrlich, PhD
Professor of Pharmacology and of Cellular And Molecular Physiology
Yale School of Medicine
Host: Stan Froehner
May
14
Thu
2020
2020 Crill Lecture – Eve Marder @ T - 625, HSB
May 14 @ 4:00 pm – 5:00 pm
  Eve Marder, Ph.D. Professor of Biology Brandeis University