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Drug Res (Stuttg) 2022; 72(05): 238-244
DOI: 10.1055/a-1785-4133
Review

Caveolins: Expression of Regulating Systemic Physiological Functions in Various Predicaments

Prabhat Kumar Upadhyay
1   Institute of Pharmaceutical Research, GLA University Mathura, UP, India
,
Vishal Kumar Vishwakarma
2   Department of Pharmacology, All India Institute of Medical Sciences, New Delhi, India
,
Ritesh Kumar Srivastav
3   Faculty of Pharmacy, Kamla Nehru Institute of Management & Technology, Sultanpur, UP, India
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Abstract

Caveolins are membrane proteins which contains caveolae. They are present in the plasma membrane. Many researchers found that caveolae have been associated with expression of the caveolins in major physiological networks of mammalian cells. Subtypes of caveolin including caveolin-1 and caveolin-2 have been found in micro arteries of rat brain, while caveolin-3 has been found in astrocytes. Caveolin-1 and caveolae play important roles in Alzheimer’s disease, cancer, ischemic preconditioning-mediated cardio-protection, postmenopausal alterations in women, and age-related neurodegeneration. Caveolin-1 may modify fatty acid transmembrane flux in adipocytes. The discovery of a link between ischemia preconditioning, cardio-protection, and endothelial nitric oxide synthase has supported cardiovascular research tremendously. Therefore, caveolins are effective in regulation of cellular, cardiovascular, brain, and immune processes. They ascertain new signalling pathways and link the functionalities of these pathways. This review paper focuses on contribution of caveolins in various conditions, caveolin expression at the molecular level and their physiological effects in many organ systems.

Keywords

caveolin - ischemic preconditioning - nitric oxide - ovariectomy - cancer progression - immunosenescence.


Publication History

Received: 26 January 2022

Accepted: 28 February 2022

Article published online:
14 April 2022

© 2022. Thieme. All rights reserved.

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  • References

  • 1 Srivastav RK, Ansari TM, Prasad M. et al. Caveolins; An Assailant or An Ally of Various Cellular Disorders. Drug Res (Stuttg) 2019; 69: 419-427
    Thieme ConnectPubMedSearch in Google Scholar
  • 2 Takaguri A, Kamato M, Satoh Y. et al. Effect of alteration of caveolin-1 expression on doxorubicin-induced apoptosis in H9c2 cardiac cells. Cell Biol Int 2015; 39: 1053-1060
    CrossrefPubMedSearch in Google Scholar
  • 3 Das M, Das DK. Caveolae, caveolin, and cavins: potential targets for the treatment of cardiac disease. Ann Med 2012; 44: 530-541
    CrossrefPubMedSearch in Google Scholar
  • 4 Fridolfsson HN, Roth DM, Insel PA. et al. Regulation of intracellular signaling and function by caveolin. FASEB J 2014; 28: 3823-3831
    CrossrefPubMedSearch in Google Scholar
  • 5 Virgintino D, Robertson D, Errede M. et al. Expression of caveolin-1 in human brain microvessels. Neuroscience 2002; 115: 145-152
    CrossrefPubMedSearch in Google Scholar
  • 6 Chakrabarti S, Morton JS, Davidge ST. Mechanisms of estrogen effects on the endothelium: an overview. Can J Cardiol 2014; 30: 705-712
    CrossrefPubMedSearch in Google Scholar
  • 7 Sun J, Zhang X, Wang C. et al. Curcumin decreases hyperphosphorylation of Tau by down-regulating Caveolin-1/GSK-3β in N2a/APP695swe cells and APP/PS1 double transgenic Alzheimer’s disease Mice. Am J Chin Med 2017; 45: 1667-1682
    CrossrefPubMedSearch in Google Scholar
  • 8 Bender F, Montoya M, Monardes V. et al. Caveolae and caveolae-like membrane domains in cellular signaling and disease: identification of downstream targets for the tumor suppressor protein caveolin-1. Biol Res 2002; 35: 151-167
    CrossrefPubMedSearch in Google Scholar
  • 9 Vallejo J, Hardin CD. Metabolic organization in vascular smooth muscle: distribution and localization of caveolin-1 and phosphofructokinase. Am J Physiol Cell Physiol 2004; 286: C43-C54
    CrossrefPubMedSearch in Google Scholar
  • 10 King DL, Arendash GW. Maintained synaptophysin immuno reactivity in “Tg2576 transgenic mice during aging: correlations with cognitive impairment. Brain Res 2002; 926: 58-68
    CrossrefPubMedSearch in Google Scholar
  • 11 Li Y, Liu LB, Ma T. et al. Effect of caveolin-1 on the expression of tight junction-associated proteins in rat glioma-derived microvascular endothelial cells. Int J Clin Exp Pathol 2015; 8: 13067-13074
    PubMedSearch in Google Scholar
  • 12 Conti E, Carrozza C, Capoluongo E. et al. Insulin-like growth factor-1 as a vascular protective factor. Circulation 2004; 110: 2260-2265
    CrossrefPubMedSearch in Google Scholar
  • 13 Versari D, Daghini E, Virdis A. et al. Endothelium-dependent contractions and endothelial dysfunction in human hypertension. Br J Pharmacol 2009; 157: 527-536
    CrossrefPubMedSearch in Google Scholar
  • 14 Foulquier S, Dupuis F, Perrin-Sarrado C. et al. Differential effects of short-term treatment with two AT1 receptor blockers on diameter of pial arterioles in SHR. PLoS One 2012; 7: e42469
    CrossrefPubMedSearch in Google Scholar
  • 15 Kypreos KE, Zafirovic S, Petropoulou PI. et al. Regulation of endothelial nitric oxide synthase and high-density lipoprotein quality by estradiol in cardiovascular pathology. J Cardiovasc Pharmacol Ther 2014; 19: 256-268
    CrossrefPubMedSearch in Google Scholar
  • 16 Goligorsky MS, Li H, Brodsky S. et al. Relationships between caveolae and eNOS: everything in proximity and the proximity of everything. Am J Physiol Renal Physiol 2002; 283: F1-F10
    CrossrefPubMedSearch in Google Scholar
  • 17 Prabhakar P, Cheng V, Michel T. A chimeric transmembrane domain directs endothelial nitric-oxide synthase palmitoylation and targeting to plasmalemmal caveolae. J Biol Chem 2000; 275: 19416-19421
    CrossrefPubMedSearch in Google Scholar
  • 18 Woodman OL, Missen MA, Boujaoude M. Diadzein and 17beta-estradiol enhance nitric oxide synthase activity associated with an increase in calmodulin and a decrease in caveolin-1. J Cardiovasc Pharm 2004; 44: 155-163
    CrossrefPubMedSearch in Google Scholar
  • 19 Batova S, DeWever J, Godfraind T. et al. The calcium channel blocker amlodipine promotes the unclamping of eNOS from caveolin in endothelial cells. Cardiovasc Res 2006; 71: 478-485
    CrossrefPubMedSearch in Google Scholar
  • 20 Razani B, Engelman JA, Wang XB. et al. Caveolin-1 null mice are viable but show evidence of hyperproliferative and vascular abnormalities. J Biol Chem 2001; 276: 38121-38138
    CrossrefPubMedSearch in Google Scholar
  • 21 Hehlgans S, Cordes N. Caveolin-1 an essential modulator of cancer cell radio-and chemoresistance. Am J Cancer Res 2011; 1: 521-530
    PubMedSearch in Google Scholar
  • 22 Roch-Arveiller M, Couderc R. Caveolae membrane domains, specialized transmembrane exchange zones implicated in cell signalling. Ann Biol Clin 2000; 58: 141-146
    PubMedSearch in Google Scholar
  • 23 Frank PG, Pavlides S, Lisanti MP. Caveolae and transcytosis in endothelial cells: role in atherosclerosis. Cell Tissue Res 2009; 335: 41-47
    CrossrefPubMedSearch in Google Scholar
  • 24 Saleh DO, El-Awdan SA, Nofel S. Estrogens improve the cardiovascular alterations in fructose-induced insulin resistant ovariectomized rats. International journal of pharmacy and pharmaceutical science 2015; 7: 241-247
    PubMedSearch in Google Scholar
  • 25 Shatz M, Liscovitch M. Caveolin-1: a tumor-promoting role in human cancer. Int J Radiat Biol 2008; 84: 177-189
    CrossrefPubMedSearch in Google Scholar
  • 26 Williams TM, Lisanti MP. Caveolin-1 in oncogenic transformation, cancer, and metastasis. Am J Physiol Cell Physiol 2005; 288: C494-C506
    CrossrefPubMedSearch in Google Scholar
  • 27 Williams TM, Hassan GS, Li J. et al. Caveolin-1 promotes tumor progression in an autochthonous mouse model of prostate cancer: genetic ablation of Cav-1 delays advanced prostate tumor development in tramp mice. J Biol Chem 2005; 280: 25134-25145
    CrossrefPubMedSearch in Google Scholar
  • 28 Wiechen K, Sers C, Agoulnik A. Down-regulation of caveolin-1, a candidate tumor suppressor gene, in sarcomas. Am J Pathol 2001; 158: 833-839
    CrossrefPubMedSearch in Google Scholar
  • 29 Witkiewicz AK. Loss of stromal caveolin-1 expression predicts poor clinical outcome in triple negative and basal-like breast cancers. Cancer Biol Ther 2010; 10: 135-143
    CrossrefPubMedSearch in Google Scholar
  • 30 Gu Y, Cai R, Zhang C. et al. miR-132-3p boosts caveolae-mediated transcellular transport in glioma endothelial cells by targeting PTEN/PI3K/PKB/Src/Cav-1 signaling pathway. FASEB J 2019; 33: 441-444
    CrossrefPubMedSearch in Google Scholar
  • 31 Chen L, Xue Y, Zheng J. et al. MiR-429 Regulated by Endothelial Monocyte Activating Polypeptide-II (EMAP-II) Influences Blood-Tumor Barrier Permeability by Inhibiting the Expressions of ZO-1, Occludin and Claudin-5. Front Mol Neurosci 2018; 11: 35
    CrossrefPubMedSearch in Google Scholar
  • 32 Neri M, Riezzo I, Pascale N. et al. Ischemia/Reperfusion Injury following Acute Myocardial Infarction: A Critical Issue for Clinicians and Forensic Pathologists. Mediators Inflamm 2017; 2017: 7018393
    CrossrefPubMedSearch in Google Scholar
  • 33 Lastra G, Syed S, Kurukulasuriya LR. et al. Type 2 diabetes mellitus and hypertension: an update. Endocrinol Metab Clin North Am 2014; 43: 103-122
    CrossrefPubMedSearch in Google Scholar
  • 34 Garlid KD, Costa AD, Quinlan CL. et al. Cardioprotective signaling to mitochondria. J Mol Cell Cardiol 2009; 46: 858-866
    CrossrefPubMedSearch in Google Scholar
  • 35 Patel HH, Murray F, Insel PA. Caveolae as organizers of pharmacologically relevant signal transduction molecules. Annu Rev Pharmacol Toxicol 2008; 48: 359-391
    CrossrefPubMedSearch in Google Scholar
  • 36 Murphy E, Steenbergen C. Mechanisms underlying acute protection from cardiac ischemia-reperfusion injury. Physiol Rev 2008; 88: 581-609
    CrossrefPubMedSearch in Google Scholar
  • 37 Sowa G. Caveolae, caveolins, cavins, and endothelial cell function: new insights. Front Physiol 2012; 2: 120
    CrossrefPubMedSearch in Google Scholar
  • 38 Li R, Cui J, Shen Y. Brain Sex Matters: estrogen in cognition and Alzheimer’s disease. Mol Cell Endocrinol 2014; 389: 13-21
    CrossrefPubMedSearch in Google Scholar
  • 39 Marin R, Diaz M. Estrogen Interactions With Lipid Rafts Related to Neuroprotection. Impact of Brain Ageing and Menopause. Front Neurosci 2018; 12: 128
    CrossrefPubMedSearch in Google Scholar
  • 40 Head BP, Peart JN, Panneerselvam M. et al. Loss of caveolin-1 accelerates neurodegeneration and aging. PLoS One 2010; 5: e15697
    CrossrefPubMedSearch in Google Scholar
  • 41 Kim J, Basak JM, Holtzman DM. The role of apolipoprotein E in Alzheimer’s disease. Neuron 2009; 63: 287-303
    CrossrefPubMedSearch in Google Scholar
  • 42 Simons K, Ehehalt R. Cholesterol, lipid rafts, and disease. J Clin Invest 2002; 110: 597-603
    CrossrefPubMedSearch in Google Scholar
  • 43 Leduc V, Jasmin-Bélanger S, Poirier J. APOE and cholesterol homeostasis in Alzheimer’s disease. Trends Mol Med 2010; 16: 469-477
    CrossrefPubMedSearch in Google Scholar
  • 44 Thompson BR, Lobo S, Bernlohr DA. Fatty acid flux in adipocytes: the in’s and out’s of fat cell lipid trafficking. Mol Cell Endocrinol 2010; 318: 24-33
    CrossrefPubMedSearch in Google Scholar
  • 45 Lo HP, Nixon SJ, Hall TE. et al. The caveolin-cavin system plays a conserved and critical role in mechanoprotection of skeletal muscle. J Cell Biol 2015; 210: 833-849
    CrossrefPubMedSearch in Google Scholar
  • 46 Nguyen KC, Cho KA. Versatile Functions of Caveolin-1 in Aging-related Diseases. Chonnam Med J 2017; 53: 28-36
    CrossrefPubMedSearch in Google Scholar
  • 47 Medina FA, de Almeida CJ, Dew E. et al. Caveolin-1-deficient mice show defects in innate immunity and inflammatory immune response during Salmonella entericaserovar Typhimurium infection. Infect Immun 2006; 74: 6665-6674
    CrossrefPubMedSearch in Google Scholar
  • 48 Lim JS, Nguyen KC, Han JM. et al. Direct Regulation of TLR5 Expression by Caveolin-1. Mol Cells 2015; 38: 1111-1117
    CrossrefPubMedSearch in Google Scholar