Surplus antioxidants are pathogenic for hearts and skeletal muscle – The Mix
By daniellenierenberg
This discovery may have clinical importance in management of heart failure.
This discovery may have clinical importance in management of heart failure.Many heart diseases are linked to oxidative stress, an overabundance of reactive oxygen species. The body reacts to reduce oxidative stress where the redox teeter-totter has gone too far up through production of endogenous antioxidants that reduce the reactive oxygen species. This balancing act is called redox homeostasis.
But what happens if the redox teeter-totter goes too far down, creating antioxidative stress, also known as reductive stress? Rajasekaran Namakkal-Soorappan, Ph.D., associate professor in the University of Alabama at Birmingham Department of Pathology, and colleagues have found that reductive stress, or RS/AS, is also pathological. This discovery, they say, may have clinical importance in management of heart failure.
They report that RS causes pathological heart enlargement and diastolic dysfunction in a mouse model. This study, published in the journal Antioxidants and Redox Signaling, was led by Namakkal-Soorappan and Pei Ping, Ph.D., David Geffen School of Medicine at the University of California-Los Angeles.
Antioxidant-based therapeutic approaches for human heart failure should consider a thorough evaluation of antioxidant levels before the treatment, they said. Our findings demonstrate that chronic RS is intolerable and adequate to induce heart failure.
The study used transgenic mice that had upregulated genes for antioxidants in the heart, which increased the amounts of antioxidant proteins and reduced glutathione, creating RS. One mouse line had low upregulation, and one had high upregulation, creating chronic low RS and chronic high RS, respectively, in the hearts of the mice.
The mice with high RS showed pathological heart changes called hypertrophic cardiomyopathy, and had an abnormally high heart ejection fraction and diastolic dysfunction at 6 months of age. Sixty percent of the high-RS mice died by 18 months of age.
The mice with low RS had normal survival rates, but they developed the heart changes at about 15 months of age, suggesting that even moderate RS can lead to irreversible damage in the heart over time.
Giving high-RS mice a chemical that blocked biosynthesis of glutathione, beginning at about 6 weeks of age, prevented RS and rescued the mice from pathological heart changes.
Gobinath Shanmugam, Ph.D., postdoctoral fellow in the UAB Department of Pathology, and Namakkal-Soorappan point out that a 2019 survey found about 77 percent of Americans are consuming dietary supplements every day, and within this group, about 58 percent are consuming antioxidants as multivitamins. Thus, a chronic consumption of antioxidant drugs by any individual without knowing their redox state might result in RS, which can induce pathology and slowly damage the heart.
In a related study, published in the journal Redox Biology, Namakkal-Soorappan looked at the impact of RS on myosatellite cells, which are also known as muscle stem cells. These cells, located near skeletal muscle fibers, are able to regenerate and differentiate into skeletal muscle after acute or chronic muscle injury. The regulation of myosatellite cells is of interest given the loss of skeletal muscle mass during aging or in chronic conditions like diabetes and AIDS.
Recently, Namakkal-Soorappan reported that tilting the redox teeter-totter to oxidative stress impaired regeneration of skeletal muscle. Now, in the Redox Biology paper, he has shown that tilting the redox to RS also causes significant inhibition of muscle satellite cell differentiation.
Rather than genetic manipulation to induce RS, as was done in the heart study, the researchers used the chemical sulforaphane or direct augmentation of intracellular glutathione to induce RS in cultured mouse myoblast cells. Both treatments inhibited myoblast differentiation. Finally, authors attempted to withdraw antioxidative stress by growing cells in medium without sulforaphane, which removes the RS and accelerates the differentiation. Namakkal-Soorappan and colleagues found that a pro-oxidative milieu, through a mild generation of reactive oxygen species, was required for myoblast differentiation.
The researchers also showed that genetic silencing of a negative regulator of the antioxidant genes also inhibited myoblast differentiation.
Co-authors with Namakkal-Soorappan and Ping, and first-author Shanmugam, in the Antioxidants and Redox Signaling study, Reductive stress causes pathological cardiac remodeling and diastolic dysfunction, are Silvio H. Litovsky and Rajesh Kumar Radhakrishnan, UAB Department of Pathology; Ding Wang, UCLA; Sellamuthu S. Gounder, Kevin Whitehead, Sarah Franklin and John R. Hoidal, University of Utah School of Medicine; Jolyn Fernandes and Dean P. Jones, Emory University, Atlanta, Georgia; Thomas W. Kensler, Fred Hutch Cancer Research Center, Seattle, Washington; Louis DellItalia, UAB Department of Medicine; Victor Darley-Usmar, UAB Department of Pathology; and E. Dale Abel, University of Iowa.
In the Redox Biology study, Reductive stress impairs myogenic differentiation, co-authors with Namakkal-Soorappan are Sandeep Balu Shelar, UAB Department of Pathology; Dean P. Jones, Emory University; and John R. Hoidal, University of Utah School of Medicine.
Support for both studies came from National Institutes of Health grants HL118067 and AG042860, American Heart Association grant BGIA 0865015F, the University of Utah, and UAB.
In the two studies, Namakkal-Soorappans name is listed as Namakkal S. Rajasekaran.
See original here:
Surplus antioxidants are pathogenic for hearts and skeletal muscle - The Mix
- 001 Cardiac Stem Cell Therapy [Last Updated On: June 24th, 2011] [Originally Added On: June 24th, 2011]
- 002 Wow! UW Research labs [Last Updated On: June 25th, 2011] [Originally Added On: June 25th, 2011]
- 003 cellalign [Last Updated On: June 28th, 2011] [Originally Added On: June 28th, 2011]
- 004 Cardiac Stem Cells in End-Stage Human Failing Hearts: Are they functional? [Last Updated On: August 25th, 2011] [Originally Added On: August 25th, 2011]
- 005 Designer Life: repair brain, heart with stem cells - Future Health keynote speaker [Last Updated On: September 4th, 2011] [Originally Added On: September 4th, 2011]
- 006 Cardiac Stem Cell Therapy at Rostock University [Last Updated On: September 4th, 2011] [Originally Added On: September 4th, 2011]
- 007 Stem Cells: Mending a broken heart? [Last Updated On: September 4th, 2011] [Originally Added On: September 4th, 2011]
- 008 Cardiovascular Derivatives of Embryonic Stem Cells in Cardiac Repair and Drug Discovery [Last Updated On: September 4th, 2011] [Originally Added On: September 4th, 2011]
- 009 Stem Cell Therapy in Cardiac Disease [Last Updated On: September 4th, 2011] [Originally Added On: September 4th, 2011]
- 010 Cardiac Recovery Points to Adult Stem Cells [Last Updated On: September 4th, 2011] [Originally Added On: September 4th, 2011]
- 011 Oral Surgeon utilizes StemSave to preserve stem cells in wisdom teeth to combat cardiac disease [Last Updated On: September 4th, 2011] [Originally Added On: September 4th, 2011]
- 012 Stem Cells and Cardiac Regeneration [Last Updated On: September 4th, 2011] [Originally Added On: September 4th, 2011]
- 013 Dr Victor Dzau on Stem Cells for Cardiac Repair. [Last Updated On: September 4th, 2011] [Originally Added On: September 4th, 2011]
- 014 Cardiomyogenic differentiation of Mesenchymal Stem cells (KUM2/9-15c) [Last Updated On: September 4th, 2011] [Originally Added On: September 4th, 2011]
- 015 Heart Failure Patient After Adult Stem Cell Therapy [Last Updated On: September 5th, 2011] [Originally Added On: September 5th, 2011]
- 016 Stem Cell operation in Cardiac Surgery-Al-Jazeerah [Last Updated On: September 7th, 2011] [Originally Added On: September 7th, 2011]
- 017 Heart Disease Patient Describes His Stem Cell Treatment [Last Updated On: September 9th, 2011] [Originally Added On: September 9th, 2011]
- 018 Cardiovascular Therapies: Spotlight on Stem Cell Research - Douglas Boyd [Last Updated On: September 16th, 2011] [Originally Added On: September 16th, 2011]
- 019 Adult Stem Cell [Last Updated On: September 20th, 2011] [Originally Added On: September 20th, 2011]
- 020 Heart repair using own stem cells after heart attack: Future Health keynote speaker [Last Updated On: September 20th, 2011] [Originally Added On: September 20th, 2011]
- 021 Stem Cell #8 Vas Cath Removal 04/28/11 [Last Updated On: September 20th, 2011] [Originally Added On: September 20th, 2011]
- 022 Adult Stem Cells Used To Rebuild Heart Tissue Video. More at http://www.stemcellfusion.com [Last Updated On: September 20th, 2011] [Originally Added On: September 20th, 2011]
- 023 Davos Question: Stem Cell Answer [Last Updated On: September 22nd, 2011] [Originally Added On: September 22nd, 2011]
- 024 Did you have a Heart Attack and Need to Recover your Cardiac Muscle? [Last Updated On: September 22nd, 2011] [Originally Added On: September 22nd, 2011]
- 025 Cardiac Tissue Can Regenerate [Last Updated On: September 22nd, 2011] [Originally Added On: September 22nd, 2011]
- 026 William F. Testimonial of Treatment Stem Cell [Last Updated On: September 23rd, 2011] [Originally Added On: September 23rd, 2011]
- 027 Stem Cell Heart Surgery must see [Last Updated On: September 24th, 2011] [Originally Added On: September 24th, 2011]
- 028 Valentine's Day Stem Cell Wish: Mending Broken Hearts [Last Updated On: September 24th, 2011] [Originally Added On: September 24th, 2011]
- 029 Advanced Cell Technology OneMedForum 2011 [Last Updated On: September 24th, 2011] [Originally Added On: September 24th, 2011]
- 030 Human 2.0: The Helix of Our Future [Last Updated On: September 24th, 2011] [Originally Added On: September 24th, 2011]
- 031 heart cell generation from human ES and iPS cells (embryonic and induced pluripotent stem cells).flv [Last Updated On: September 24th, 2011] [Originally Added On: September 24th, 2011]
- 032 Stem Cell Therapy and Stem Cell Treatment with Dell [Last Updated On: September 24th, 2011] [Originally Added On: September 24th, 2011]
- 033 UCD Med Student Receives Fulbright Award [Last Updated On: September 24th, 2011] [Originally Added On: September 24th, 2011]
- 034 Cardiomyocytes derived from mouse Embryonic stem cells [Last Updated On: September 25th, 2011] [Originally Added On: September 25th, 2011]
- 035 Immune Control of Stem Cell Mobilization [Last Updated On: September 25th, 2011] [Originally Added On: September 25th, 2011]
- 036 Better Drugs Through Stem Cells [Last Updated On: September 25th, 2011] [Originally Added On: September 25th, 2011]
- 037 stem cell derived cardiomyocytes [Last Updated On: September 25th, 2011] [Originally Added On: September 25th, 2011]
- 038 Stem Cells: Heart cells grown from mouse stem cells [Last Updated On: September 25th, 2011] [Originally Added On: September 25th, 2011]
- 039 Patel Stem Cell Heart Failure [Last Updated On: September 25th, 2011] [Originally Added On: September 25th, 2011]
- 040 Turning Adult Stem Cells into Medicine - Zannos Grekos, MD [Last Updated On: September 25th, 2011] [Originally Added On: September 25th, 2011]
- 041 Kevin's 2 Heart Transplants and Stem Cell Transplant [Last Updated On: September 25th, 2011] [Originally Added On: September 25th, 2011]
- 042 Breakthrough in Stem cell technology [Last Updated On: September 25th, 2011] [Originally Added On: September 25th, 2011]
- 043 Affordable Stem Cell Therapy in Guatemala (2hrs from Miami) [Last Updated On: September 26th, 2011] [Originally Added On: September 26th, 2011]
- 044 Cadiomyogenesis of human mesenchymal stem cells [Last Updated On: September 26th, 2011] [Originally Added On: September 26th, 2011]
- 045 Mark Mercola: Differentiating embryonic stem cells into adult tissues [Last Updated On: September 26th, 2011] [Originally Added On: September 26th, 2011]
- 046 Cardiomyocytic differentiation of endometrial stem cells. [Last Updated On: September 26th, 2011] [Originally Added On: September 26th, 2011]
- 047 Adult Stem Cell vs Embryonic Stem Cell Research Ethics Video [Last Updated On: September 26th, 2011] [Originally Added On: September 26th, 2011]
- 048 Pt. 1--Dr. Ali Denktas--Stem Cells as Markers after Myocardial Infarctions [Last Updated On: September 27th, 2011] [Originally Added On: September 27th, 2011]
- 049 Repairing Damaged Hearts with Stem Cells [Last Updated On: September 29th, 2011] [Originally Added On: September 29th, 2011]
- 050 Mouse GEN cells overexpressing Csx/Nkx2.5 and GATA4 behave like transient amplifying cells [Last Updated On: September 29th, 2011] [Originally Added On: September 29th, 2011]
- 051 20100804_axiogenesis.wmv [Last Updated On: September 29th, 2011] [Originally Added On: September 29th, 2011]
- 052 Beating Cardiomyocytes from E14 Cells [Last Updated On: September 29th, 2011] [Originally Added On: September 29th, 2011]
- 053 Heart cells grown from human embryonic stem cells [Last Updated On: September 29th, 2011] [Originally Added On: September 29th, 2011]
- 054 First US Patient In Stem Cell Transplant [Last Updated On: September 29th, 2011] [Originally Added On: September 29th, 2011]
- 055 Be still my beating stem cell heart [Last Updated On: October 1st, 2011] [Originally Added On: October 1st, 2011]
- 056 Beating Human Heart Cells from Embryonic Stem Cells [Last Updated On: October 1st, 2011] [Originally Added On: October 1st, 2011]
- 057 Spontaneously and rhythmically beating engineered human heart tissue from pluripotent stem cells [Last Updated On: October 3rd, 2011] [Originally Added On: October 3rd, 2011]
- 058 Cardiac Stem Cell Therapy - How it works [Last Updated On: October 3rd, 2011] [Originally Added On: October 3rd, 2011]
- 059 Doctors To Use 'Trained' Stem Cells To Heal Heart [Last Updated On: October 5th, 2011] [Originally Added On: October 5th, 2011]
- 060 Beating Heart Stem Cells [Last Updated On: October 5th, 2011] [Originally Added On: October 5th, 2011]
- 061 AM RADIO, DR. AMIT PATEL AND STEM CELLS SAVED MY LIFE - Video [Last Updated On: October 14th, 2011] [Originally Added On: October 14th, 2011]
- 062 New heart built with stem cells - Video [Last Updated On: October 15th, 2011] [Originally Added On: October 15th, 2011]
- 063 Adult Stem Cells For Heart Disease: Today's Reality - Video [Last Updated On: October 15th, 2011] [Originally Added On: October 15th, 2011]
- 064 H9 beating stem cells - Video [Last Updated On: October 27th, 2011] [Originally Added On: October 27th, 2011]
- 065 Double Blind Trial of Stem Cells for Heart Failure - Video [Last Updated On: October 27th, 2011] [Originally Added On: October 27th, 2011]
- 066 Repairing Damaged Hearts with Stem Cells - Video [Last Updated On: October 27th, 2011] [Originally Added On: October 27th, 2011]
- 067 Cardiac differentiation of hES cells at 20x - Video [Last Updated On: October 27th, 2011] [Originally Added On: October 27th, 2011]
- 068 SPRAY-ON STEM CELLS - Video [Last Updated On: October 28th, 2011] [Originally Added On: October 28th, 2011]
- 069 Stem Cells: A smart use for wisdom teeth - Video [Last Updated On: November 12th, 2011] [Originally Added On: November 12th, 2011]
- 070 VistaGen's Stem Cell Derived Cardiomyocytes - Video [Last Updated On: November 12th, 2011] [Originally Added On: November 12th, 2011]
- 071 Stem Cell Research [Last Updated On: November 12th, 2011] [Originally Added On: November 12th, 2011]
- 072 The Power of Stem Cells - Video [Last Updated On: November 12th, 2011] [Originally Added On: November 12th, 2011]
- 073 Beating iCellĀ® Cardiomyocytes - Video [Last Updated On: November 13th, 2011] [Originally Added On: November 13th, 2011]
- 074 SCIPIO: Cardiac stem cells and postinfarction heart failure - Video [Last Updated On: November 15th, 2011] [Originally Added On: November 15th, 2011]
- 075 Beating Cardiomyocytes in Cell Culture - Video [Last Updated On: November 15th, 2011] [Originally Added On: November 15th, 2011]
- 076 Stem Cells Heal Heart Attack Damage. - Video [Last Updated On: December 7th, 2011] [Originally Added On: December 7th, 2011]
- 077 C2CAM - 2011.11.15 - Dulce Base - Regenerative Medicine - Info - Video [Last Updated On: December 7th, 2011] [Originally Added On: December 7th, 2011]
- 078 Latest Update on Stem Cell Research at UW - Dr. Timothy Kamp - Video [Last Updated On: December 7th, 2011] [Originally Added On: December 7th, 2011]
- 079 Coast To Coast AM: Regenerative Medicine / Dulce Base 11-15-2011 Download Link - Video [Last Updated On: December 7th, 2011] [Originally Added On: December 7th, 2011]
- 080 C2CAM - 2011.11.15 - Dulce Base - Regenerative Medicine - Video [Last Updated On: December 7th, 2011] [Originally Added On: December 7th, 2011]
