Indrani Sinha-Hikim, PhD
Title Associate Professor
Institution Charles R. Drew University of Medicine and Science
Department Internal Medicine
School College of Medicine
Address 1731 E. 120th Street, Hawkins Building


Telephone (323) 563-5959
Fax
Email
Overview
1. Cardiac consequences of prenatal cocaine exposure: The central hypotheses of the proposal are: i) that prenatal cocaine exposure induces cardiac myocyte apoptosis through activation of JNK/p38 MAPK-mediated mitochondria-dependent pathway and ii) minocycline, through inhibition of this signal transduction pathway, will confer protection in cardiac myocyte death induced by prenatal cocaine exposure. Specific aims contain characterization of the key molecular components of the JNK/p38-mediated apoptotic pathway in myocyte death and its mitigation by minocycline or JNK inhibitor. Results of this study will provide insight into the underlying mechanism of cardiac myocyte death that occurs in offspring after prenatal cocaine exposure. Identifying signaling pathways leading to myocyte death paves the way to design therapeutic remedies to myocyte death and, in turn, cardiac consequences of prenatal cocaine exposure. 2. Molecular Mechanism of Sarcopenia and its Prevention: Sarcopenia is defined as the progressive decline of skeletal muscle mass and strength, which occurs with aging. I was able to show for the first time that testosterone-induced increase in muscle size is associated with fiber hypertrophy and significant increases in myonuclear and satellite cell numbers in both young and old men (Sinha-Hikim et al., Am J Physiol Endocrinol Metab 2002, 2003; Sinha-Hikim et al., J Clin Endocrinol Metab 2006). My laboratory, using mouse models, has provided new insights into the molecular mechanisms of muscle cell apoptosis (Sinha-Hikim et al, Apoptosis, 2007; Braga et al., Apoptosis, 2008). We were also the first team to provide mechanistic insights by which testosterone supplement may induce skeletal muscle fiber hypertrophy (Brown et al, J Endocrinol, 2009; Kovacheva et al., Endocrinology, 2010). This information is crucial for understanding the skeletal muscle pathophysiology in aging and for further research directed toward clinical management of successful aging, which could lay a foundation based on which rational hormone replacement therapy could be designed for delaying or preventing loss of muscle mass in elderly men as well as in other wasting states. 3. Use of a Novel Antioxidant as a Part of Dietary supplement: The search for natural products that are culturally acceptable and understanding their mechanisms of action is a critical component in the fight to reduce health disparities and improve the overall health of the nation. Nonalcoholic fatty liver disease (NFLD) includes the whole spectrum of fatty liver, including steatosis, steatohepatitis, and cirrhosis. Oxidative stress is pivotal in the pathogenesis of NFLD. We examined the effects of a novel cystine based glutathione precursor fortified with selenium (FT061452 TM or F1) in preventing steatosis in ApoE-/- mice fed with high-fat diet. The results demonstrate that dietary supplementation of F1, a modified glutathione precursor prevents high fat diet-induced induced steatosis in ApoE-/- mice and emphasizes the suitability of this model for investigating the mechanisms of diet-induced steatosis.
Education & Training
Teaching
NIH Awarded Grants
Project TitleProject NumberFY
HORMONE ASSAY CORE3P20RR011145-14S22009
HORMONE ASSAY CORE5P20RR011145-142008
Testosterone Action on Muscle Injury and Repair3S06GM068510-02S42005
Publications
1. Hasan KM, Friedman TC, Shao X, Parveen M, Sims C, Lee DL, Espinoza-Derout J, Sinha-Hikim I, Sinha-Hikim AP. E-cigarettes and Western Diet: Important Metabolic Risk Factors for Hepatic Diseases. Hepatology. 2019 06; 69(6):2442-2454.
  View in: PubMed
 
2. Hasan MK, Friedman TC, Sims C, Lee DL, Espinoza-Derout J, Ume A, Chalfant V, Lee ML, Sinha-Hikim I, Lutfy K, Liu Y, Mahata SK, Sinha-Hikim AP. a7-Nicotinic Acetylcholine Receptor Agonist Ameliorates Nicotine Plus High-Fat Diet-Induced Hepatic Steatosis in Male Mice by Inhibiting Oxidative Stress and Stimulating AMPK Signaling. Endocrinology. 2018 02 01; 159(2):931-944.
  View in: PubMed
 
3. Sinha-Hikim AP, Sinha-Hikim I, Friedman TC. Connection of Nicotine to Diet-Induced Obesity and Non-Alcoholic Fatty Liver Disease: Cellular and Mechanistic Insights. Front Endocrinol (Lausanne). 2017; 8:23.
  View in: PubMed
 
4. Sinha-Hikim I, Friedman TC, Falz M, Chalfant V, Hasan MK, Espinoza-Derout J, Lee DL, Sims C, Tran P, Mahata SK, Sinha-Hikim AP. Nicotine plus a high-fat diet triggers cardiomyocyte apoptosis. Cell Tissue Res. 2017 04; 368(1):159-170.
  View in: PubMed
 
5. Sinha I, Sinha-Hikim AP, Wagers AJ, Sinha-Hikim I. Testosterone is essential for skeletal muscle growth in aged mice in a heterochronic parabiosis model. Cell Tissue Res. 2014 Sep; 357(3):815-21.
  View in: PubMed
 
6. Sinha-Hikim I, Friedman TC, Shin CS, Lee D, Ivey R, Sinha-Hikim AP. Nicotine in combination with a high-fat diet causes intramyocellular mitochondrial abnormalities in male mice. Endocrinology. 2014 Mar; 155(3):865-72.
  View in: PubMed
 
7. Sinha-Hikim I, Sinha-Hikim AP, Parveen M, Shen R, Goswami R, Tran P, Crum A, Norris KC. Long-term supplementation with a cystine-based antioxidant delays loss of muscle mass in aging. J Gerontol A Biol Sci Med Sci. 2013 Jul; 68(7):749-59.
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8. Friedman TC, Sinha-Hikim I, Parveen M, Najjar SM, Liu Y, Mangubat M, Shin CS, Lyzlov A, Ivey R, Shaheen M, French SW, Sinha-Hikim AP. Additive effects of nicotine and high-fat diet on hepatic steatosis in male mice. Endocrinology. 2012 Dec; 153(12):5809-20.
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9. Mangubat M, Lutfy K, Lee ML, Pulido L, Stout D, Davis R, Shin CS, Shahbazian M, Seasholtz S, Sinha-Hikim A, Sinha-Hikim I, O'Dell LE, Lyzlov A, Liu Y, Friedman TC. Effect of nicotine on body composition in mice. J Endocrinol. 2012 Mar; 212(3):317-26.
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10. Sinha-Hikim I, Shen R, Nzenwa I, Gelfand R, Mahata SK, Sinha-Hikim AP. Minocycline suppresses oxidative stress and attenuates fetal cardiac myocyte apoptosis triggered by in utero cocaine exposure. Apoptosis. 2011 Jun; 16(6):563-73.
  View in: PubMed
 
11. Sinha-Hikim I, Sinha-Hikim AP, Shen R, Kim HJ, Kim H, French SW, Vaziri ND, Vaziri ND, Crum AC, Crum A, Rajavashisth TB, Norris KC. A novel cystine based antioxidant attenuates oxidative stress and hepatic steatosis in diet-induced obese mice. Exp Mol Pathol. 2011 Aug; 91(1):419-28.
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12. Sinha-Hikim I, Shen R, Paul Lee WN, Crum A, Vaziri ND, Norris KC. Effects of a novel cystine-based glutathione precursor on oxidative stress in vascular smooth muscle cells. Am J Physiol Cell Physiol. 2010 Sep; 299(3):C638-42.
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13. Sinha-Hikim I, Shen R, Kovacheva E, Crum A, Vaziri ND, Norris KC. Inhibition of apoptotic signalling in spermine-treated vascular smooth muscle cells by a novel glutathione precursor. Cell Biol Int. 2010 Apr 01; 34(5):503-11.
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14. Kovacheva EL, Hikim AP, Shen R, Sinha I, Sinha-Hikim I. Testosterone supplementation reverses sarcopenia in aging through regulation of myostatin, c-Jun NH2-terminal kinase, Notch, and Akt signaling pathways. Endocrinology. 2010 Feb; 151(2):628-38.
  View in: PubMed
 
15. Brown D, Hikim AP, Kovacheva EL, Sinha-Hikim I. Mouse model of testosterone-induced muscle fiber hypertrophy: involvement of p38 mitogen-activated protein kinase-mediated Notch signaling. J Endocrinol. 2009 Apr; 201(1):129-39.
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16. Jia Y, Castellanos J, Wang C, Sinha-Hikim I, Lue Y, Swerdloff RS, Sinha-Hikim AP. Mitogen-activated protein kinase signaling in male germ cell apoptosis in the rat. Biol Reprod. 2009 Apr; 80(4):771-80.
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17. Braga M, Sinha Hikim AP, Datta S, Ferrini MG, Brown D, Kovacheva EL, Gonzalez-Cadavid NF, Sinha-Hikim I. Involvement of oxidative stress and caspase 2-mediated intrinsic pathway signaling in age-related increase in muscle cell apoptosis in mice. Apoptosis. 2008 Jun; 13(6):822-32.
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18. Sinha-Hikim I, Braga M, Shen R, Sinha Hikim AP. Involvement of c-Jun NH2-terminal kinase and nitric oxide-mediated mitochondria-dependent intrinsic pathway signaling in cardiotoxin-induced muscle cell death: role of testosterone. Apoptosis. 2007 Nov; 12(11):1965-78.
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19. Herbst KL, Calof OM, Hsia SH, Sinha-Hikim I, Woodhouse LJ, Buchanan TA, Bhasin S. Effects of transdermal testosterone administration on insulin sensitivity, fat mass and distribution, and markers of inflammation and thrombolysis in human immunodeficiency virus-infected women with mild to moderate weight loss. Fertil Steril. 2006 Jun; 85(6):1794-802.
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20. Sinha-Hikim I, Cornford M, Gaytan H, Lee ML, Bhasin S. Effects of testosterone supplementation on skeletal muscle fiber hypertrophy and satellite cells in community-dwelling older men. J Clin Endocrinol Metab. 2006 Aug; 91(8):3024-33.
  View in: PubMed
 
21. Singh AB, Lee ML, Sinha-Hikim I, Kushnir M, Meikle W, Rockwood A, Afework S, Bhasin S. Pharmacokinetics of a testosterone gel in healthy postmenopausal women. J Clin Endocrinol Metab. 2006 Jan; 91(1):136-44.
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22. Gray PB, Singh AB, Woodhouse LJ, Storer TW, Casaburi R, Dzekov J, Dzekov C, Sinha-Hikim I, Bhasin S. Dose-dependent effects of testosterone on sexual function, mood, and visuospatial cognition in older men. J Clin Endocrinol Metab. 2005 Jul; 90(7):3838-46.
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23. Bhasin S, Woodhouse L, Casaburi R, Singh AB, Mac RP, Lee M, Yarasheski KE, Sinha-Hikim I, Dzekov C, Dzekov J, Magliano L, Storer TW. Older men are as responsive as young men to the anabolic effects of graded doses of testosterone on the skeletal muscle. J Clin Endocrinol Metab. 2005 Feb; 90(2):678-88.
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24. Jasuja R, Ramaraj P, Mac RP, Singh AB, Storer TW, Artaza J, Miller A, Singh R, Taylor WE, Lee ML, Davidson T, Sinha-Hikim I, Gonzalez-Cadavid N, Bhasin S. Delta-4-androstene-3,17-dione binds androgen receptor, promotes myogenesis in vitro, and increases serum testosterone levels, fat-free mass, and muscle strength in hypogonadal men. J Clin Endocrinol Metab. 2005 Feb; 90(2):855-63.
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25. Sinha-Hikim I, Taylor WE, Gonzalez-Cadavid NF, Zheng W, Bhasin S. Androgen receptor in human skeletal muscle and cultured muscle satellite cells: up-regulation by androgen treatment. J Clin Endocrinol Metab. 2004 Oct; 89(10):5245-55.
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26. Bhasin S, Taylor WE, Singh R, Artaza J, Sinha-Hikim I, Jasuja R, Choi H, Gonzalez-Cadavid NF. The mechanisms of androgen effects on body composition: mesenchymal pluripotent cell as the target of androgen action. J Gerontol A Biol Sci Med Sci. 2003 Dec; 58(12):M1103-10.
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27. Reisz-Porszasz S, Bhasin S, Artaza JN, Shen R, Sinha-Hikim I, Hogue A, Fielder TJ, Gonzalez-Cadavid NF. Lower skeletal muscle mass in male transgenic mice with muscle-specific overexpression of myostatin. Am J Physiol Endocrinol Metab. 2003 Oct; 285(4):E876-88.
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28. Sinha-Hikim I, Roth SM, Lee MI, Bhasin S. Testosterone-induced muscle hypertrophy is associated with an increase in satellite cell number in healthy, young men. Am J Physiol Endocrinol Metab. 2003 Jul; 285(1):E197-205.
  View in: PubMed
 
29. Schroeder ET, Singh A, Bhasin S, Storer TW, Azen C, Davidson T, Martinez C, Sinha-Hikim I, Jaque SV, Terk M, Sattler FR. Effects of an oral androgen on muscle and metabolism in older, community-dwelling men. Am J Physiol Endocrinol Metab. 2003 Jan; 284(1):E120-8.
  View in: PubMed
 
30. Sinha-Hikim I, Artaza J, Woodhouse L, Gonzalez-Cadavid N, Singh AB, Lee MI, Storer TW, Casaburi R, Shen R, Bhasin S. Testosterone-induced increase in muscle size in healthy young men is associated with muscle fiber hypertrophy. Am J Physiol Endocrinol Metab. 2002 Jul; 283(1):E154-64.
  View in: PubMed
 
31. Singh AB, Hsia S, Alaupovic P, Sinha-Hikim I, Woodhouse L, Buchanan TA, Shen R, Bross R, Berman N, Bhasin S. The effects of varying doses of T on insulin sensitivity, plasma lipids, apolipoproteins, and C-reactive protein in healthy young men. J Clin Endocrinol Metab. 2002 Jan; 87(1):136-43.
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Funding Opportunities

Click terms below for current NIH/NSF funding opportunities.
  • Testosterone


  • Muscle, Skeletal


  • Oxidative Stress


  • Apoptosis


  • Muscle Fibers, Skeletal


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Keyword
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Keywords   
Testosterone
Muscle, Skeletal
Oxidative Stress
Apoptosis
Muscle Fibers, Skeletal
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Co-Authors  
Artaza, Jorge
Espinoza-Derout, Jorge
Friedman, Theodore
Gonzalez-Cadavid, Nestor
Sinha-Hikim, Amiya
See all (15) people
Physical Neighbors  
Davidson, Mayer
Gonzalez-Cadavid, Nestor
Sinha, Satyesh
Friedman, Theodore
Rajavashisth, Tripathi


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