Download PDF
Drug Res (Stuttg) 2019; 69(08): 419-427
DOI: 10.1055/a-0850-6518
Review
© Georg Thieme Verlag KG Stuttgart · New York

Caveolins; An Assailant or An Ally of Various Cellular Disorders

Ritesh Kumar Srivastav
1   Faculty of Pharmacy, Kamla Nehru Institute of Management and Technology, Sultanpur, India
,
Tarique Mahmood Ansari
2   Faculty of Pharmacy, Integral University, Lucknow, Uttar Pradesh, India
,
Mahesh Prasad
1   Faculty of Pharmacy, Kamla Nehru Institute of Management and Technology, Sultanpur, India
,
Vishal Kumar Vishwakarma
3   Department of Pharmacology, R.R.S College of Pharmacy, Amethi, Uttar Pradesh, India
,
Paramdeep Bagga
2   Faculty of Pharmacy, Integral University, Lucknow, Uttar Pradesh, India
,
Farogh Ahsan
2   Faculty of Pharmacy, Integral University, Lucknow, Uttar Pradesh, India
› Author Affiliations
Further Information

Publication History

received 01 January 2019

accepted 01 February 2019

Publication Date:
18 February 2019 (online)

Also available at
   Permissions and Reprints

Abstract

Caveolae have impressive morphological highlights of the cytomembrane of mammalian cells which involve in wide diversity of cellular functions involving signaling pathways and cholesterol hastening. Caveolin proteins possess a ‘scaffolding’ domain which for caveolin-1 and caveolin-3 appear to act a dominant role in signal regulation through caveolae. Caveolin-1 is treated to be protein in the cytomembrane entrapped with caveolae in endothelial cells and vascular smooth muscle cells which diminish nitric oxide (NO) by fill up the calcium/calmodulin (Ca2+/CaM) confining point of endothelial nitric oxide synthase (eNOS), decrease NO generation produce endothelial dysfunction and atherosclerotic injury development. It is a cholesterol-binding layer protein associated with cell cholesterol transport and also shows cardioprotective action through ischemic preconditioning (IPC) in diabetic and postmenopausal rat heart. Additionally it is ensnared in the procedures of tumorigenesis, prostate disease, and inflammation. The present study in the paper is to explore the structural functionalities of caveolins and their contributory role in CVS disorders and various other diseases.

Key words

caveolins - cardiovascular disorder - diabetic - ischaemic preconditioning - nitric oxide - cell growth
 

  • References

  • 1 Pilch PF, Meshulam T, Ding S. et al. Caveolae and lipid trafficking in adipocytes. Clin Lipidol 2011; 6: 49-58
    CrossrefPubMedGoogle Scholar
  • 2 Yamada E. The fine structure of the gall bladder epithelium of the mouse. J Biophys Biochem Cytol 1955; 1: 445-458
    CrossrefPubMedGoogle Scholar
  • 3 Palade GE. Fine structure of blood capillaries. J Appl Physics 1953; 24: 14-24
    PubMedGoogle Scholar
  • 4 Thomas CM, Smart EJ. Caveolae structure and function. J Cell Mol Med 2008; 12: 796-809
    CrossrefPubMedGoogle Scholar
  • 5 Thorn H, Stenkula KG, Karlsson M. et al. Cell surface orifices of caveolae and localization of caveolin to the necks of caveolae in adipocytes. Mol Biol Cell 2003; 14: 3967-3976
    CrossrefPubMedGoogle Scholar
  • 6 Moos T. Brain iron homeostasis. Dan Med Bull 2002; 49: 279-301
    PubMedGoogle Scholar
  • 7 Kiss AL, Turi A, Muller N. et al. Caveolae and caveolin isoforms in rat peritoneal macrophages. Micron 2002; 33: 75-93
    CrossrefPubMedGoogle Scholar
  • 8 Balijepalli RC, Kamp TJ. Caveolae, ion channels and cardiac arrhythmias. Prog biophys Mol Biol 2008; 98: 149-160
    CrossrefPubMedGoogle Scholar
  • 9 Parton RG, Simons K. The multiple faces of caveolae. Nat Rev Mol Cell Biol 2007; 8: 185-194
    CrossrefPubMedGoogle Scholar
  • 10 Smart EJ, Graf GA, McNiven MA. et al. Caveolins, liquid-ordered domains, and signal transduction. Mol Cell Biol 1999; 19: 7289-7304
    CrossrefPubMedGoogle Scholar
  • 11 Halayko AJ, Stelmack GL. The association of caveolae, actin, and the dystrophin-glycoprotein complex: A role in smooth muscle phenotype and function?. Can J Physiol Pharmacol 2005; 83: 877-891
    CrossrefPubMedGoogle Scholar
  • 12 Das M, Das DK. Caveolae, caveolin, and cavins: Potential targets for the treatment of cardiac disease. Ann Med 2012; 44: 530-541
    CrossrefPubMedGoogle Scholar
  • 13 Ajmani P, Yadav HN. Possible involvement of caveolin in attenuation of cardioprotective effect of ischemic preconditioning in diabetic rat heart. BMC Cardiovasc. Disord 2011; 11: 43
    CrossrefPubMedGoogle Scholar
  • 14 Machleidt T, Li WP, Liu P. et al. Multiple domains in caveolin-1 control its intracellular traffic. J Cell Biol 2000; 148: 17-28
    CrossrefPubMedGoogle Scholar
  • 15 Lisanti MP, Tang ZL, Sargiacomo M. Caveolin forms a hetero-oligomeric protein complex that interacts with an apical GPI-linked protein: implications for the biogenesis of caveolae. J Cell Biol 1993; 123: 595-604
    CrossrefPubMedGoogle Scholar
  • 16 Uittenbogaard A, Smart EJ. Palmitoylation of caveolin-1 is required for cholesterol binding, chaperone complex formation, and rapid transport of cholesterol to caveolae. J Biol Chem 2000; 275: 25595-25599
    CrossrefPubMedGoogle Scholar
  • 17 Vinten J, Voldstedlund M, Clausen H. et al. A 60- kDa protein abundant in adipocyte caveolae. Cell Tissue Res 2001; 305: 99-106
    CrossrefPubMedGoogle Scholar
  • 18 Jansa P, Mason SW, Hoffmann-Rohrer U. et al. Cloning and functional characterization of PTRF, a novel protein which induces dissociation of paused ternary transcription complexes. EMBO J 1998; 17: 2855-2864
    CrossrefPubMedGoogle Scholar
  • 19 Hasegawa T, Takeuchi A, Miyaishi O. et al. PTRF (polymerase I and transcriptrelease factor) is tissue-specific and interacts with the BFCOL1 (binding factor of a type-I collagen promoter) zinc-finger transcription factor which binds to the two mouse type-I collagen gene promoters. Biochem J 2000; 347: 55-59
    CrossrefPubMedGoogle Scholar
  • 20 Vinten J, Johnsen AH, Roepstorff P. et al. Identification of a major protein on the cytosolic face of caveolae. Biochim Biophys Acta 2005; 1717: 34-40
    PubMedGoogle Scholar
  • 21 Chang WJ, Rothberg KG, Kamen BA. et al. Lowering the cholesterol content of MA104 cells inhibits receptor-mediated transport of folate. J Cell Biol 1992; 118: 63-69
    CrossrefPubMedGoogle Scholar
  • 22 Thyberg J, Calara F, Dimayuga P. et al. Role of caveolae in cholesterol transport in arterial smooth muscle cells exposed to lipoproteins in vitro and in vivo. Lab Invest 1998; 78: 825-837
    PubMedGoogle Scholar
  • 23 Hailstones D, Sleer LS, Parton RG. et al. Regulation of caveolin and caveolae by cholesterol in MDCK cells. J Lipid Res 1998; 39: 369-379
    CrossrefPubMedGoogle Scholar
  • 24 Smart EJ, Ying YS, Conrad PA. et al. Caveolin moves from caveolae to the Golgi apparatus in response to cholesterol oxidation. J Cell Biol 1994; 127: 1185-1197
    CrossrefPubMedGoogle Scholar
  • 25 Li S, Couet J, Lisanti MP. Src tyrosine kinases, Galpha subunits, and H-Ras share a common membrane-anchored scaffolding protein, caveolin. Caveolin binding negatively regulates the auto-activation of Src tyrosine kinases. J Biol Chem 1996; 271: 9182-29190
    PubMedGoogle Scholar
  • 26 Schlegel A, Lisanti MP. The caveolin triad: caveolae biogenesis, cholesterol trafficking, and signal transduction. Cytokine Growth Factor Rev 2001; 12: 41-51
    CrossrefPubMedGoogle Scholar
  • 27 Arnal JF, Dinh-Xuan AT, Pueyo M. et al. Endothelium-derived nitric oxide and vascular physiology and pathology. Cell Mol Life Sci 1999; 55: 1078-1087
    CrossrefPubMedGoogle Scholar
  • 28 Andrew PJ, Mayer B. Enzymatic function of nitric oxide synthases. Cardiovasc Res 1999; 43: 521-531
    CrossrefPubMedGoogle Scholar
  • 29 Shaul PW. Endothelial nitric oxide synthase, caveolae and the development of atherosclerosis. J Physiol 2003; 547: 21-33
    CrossrefPubMedGoogle Scholar
  • 30 Balligand JL, Kobzik L, Han X. et al. Nitric oxide-dependent parasympathetic signaling is due to activation of constitutive endothelia (type III) nitric oxide synthase in cardiac myocytes. J Biol Chem 1995; 270: 14582-14586
    CrossrefPubMedGoogle Scholar
  • 31 Garcia-Cardena G, Martasek P, Masters BS. et al. Dissecting the interaction between nitric oxide synthase (NOS) and caveolin. Functional significance of the nos caveolin binding domain in vivo. J Biol Chem 1997; 272: 25437-2544
    CrossrefPubMedGoogle Scholar
  • 32 Campbell L, Gumbleton M, Ritchie K. Caveolae and the caveolins in human disease. Physiol Rev 2004; 84: 1341-1379
    CrossrefPubMedGoogle Scholar
  • 33 Bender SB, Jia G, Sowers JR. Mineralocorticoid receptors: An appealing target to treat coronary microvascular dysfunction in diabetes. Diabetes 2015; 64: 3-5
    CrossrefPubMedGoogle Scholar
  • 34 Seto SW, Krishna SM, Yu H. et al. Impaired acetylcholine-induced endothelium-dependent aortic relaxation by caveolin-1 in angiotensin II-infused apolipoprotein-E (ApoE-/-) knockout mice. PLoS One 2013; 8: e58481
    CrossrefPubMedGoogle Scholar
  • 35 Sharma A, Sellers S, Stefanovic N. et al. Direct endothelial nitric oxide synthase activation provides atheroprotection in diabetes-accelerated atherosclerosis. Diabetes 2015; 64: 3937-3950
    CrossrefPubMedGoogle Scholar
  • 36 Jia G, Sowers JR. Caveolin-1 in cardiovascular disease: A double-edged sword. Diabetes 2015; 64: 3645-3747
    CrossrefPubMedGoogle Scholar
  • 37 Breton S, Lisanti MP, Tyszkowski R. et al. Basolateral distribution of caveolin-1 in the kidney. Absence from H+-atpase-coated endocytic vesicles in intercalated cells. J Histochem. Cytochem 1998; 46: 205-214
    CrossrefPubMedGoogle Scholar
  • 38 Wang L, Zhang C, Su X. et al. Caveolin-1 defciency inhibits the basolateral K+channels in the distal convoluted tubule and impairs renal k+and Mg2+transport. J Am Soc Nephrol 2015; 26: 2678-2690
    CrossrefPubMedGoogle Scholar
  • 39 Paunescu TG, Lu HA, Russo LM. et al. Vasopressin induces apical expression of caveolin in rat kidney collecting duct principal cells. Am J Physiol Renal Physiol 2013; 305: F1783-F1795
    CrossrefPubMedGoogle Scholar
  • 40 Chen Z, Bakhshi FR, Shajahan AN. et al. Nitric oxide-dependent Src activation and resultant caveolin-1 phosphorylation promote eNOS/caveolin-1 binding and eNOS inhibition. Mol Biol Cell 2012; 23: 1388-1398
    CrossrefPubMedGoogle Scholar
  • 41 Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell 2011; 144: 646-674
    CrossrefPubMedGoogle Scholar
  • 42 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: 25134-15145
    CrossrefPubMedGoogle Scholar
  • 43 Quann K, Gonzales DM, Mercier I. et al Caveolin-1 is a negative regulator of tumor growth in glioblastoma and modulates chemosensitivity to temozolomide. Cell Cycle 2013; 12: 1510-1520
    CrossrefPubMedGoogle Scholar
  • 44 McLaughlin N, Annabi B, Bouzeghrane M. et al. The Survivin-mediated radioresistant phenotype of glioblastomas is regulated by RhoA and inhibited by the green tea polyphenol (-)-epigallocatechin-3-gallate. Brain Res 2006; 1071: 1-9
    CrossrefPubMedGoogle Scholar
  • 45 Shatz M, Liscovitch M. Caveolin-1: a tumor-promoting role in human cancer. Int J Radiat Biol 2008; 84: 177-189
    CrossrefPubMedGoogle Scholar
  • 46 Yang G, Truong LD, Wheeler TM. et al. Caveolin-1 expression in clinically confined human prostate cancer: a novel prognostic marker. Cancer Res 1999; 59: 5719-5723
    PubMedGoogle Scholar
  • 47 Ho CC, Huang PH, Huang HY. et al. Up-regulated caveolin-1 accentuates the metastasis capability of lung adenocarcinoma by inducing filopodia formation. Am J Pathol 2002; 161: 1647-1656
    CrossrefPubMedGoogle Scholar
  • 48 Joo HJ, Oh DK, Kim YS. et al. Increased expression of caveolin1 and microvessel density correlates with metastasis and poor prognosis in clear cell renal cell carcinoma. BJU Int 2004; 93: 291-296
    CrossrefPubMedGoogle Scholar
  • 49 Kato K, Hida Y, Miyamoto M. et al. Overexpression of caveolin-1 in esophageal squamous cell carcinoma correlates with lymph node metastasis and pathologic stage. Cancer 2002; 94: 929-933
    CrossrefPubMedGoogle Scholar
  • 50 Couet J, Sargiacomo M, Lisanti MP. Interaction of a receptor tyrosine kinase, EGF-R, with caveolins. Caveolin binding negatively regulates tyrosine and serine/threonine kinase activities. J Biol Chem 1997; 272: 30429-30438
    CrossrefPubMedGoogle Scholar
  • 51 Eldar-Finkelman H, Krebs EG. Phosphorylation of insulin receptor substrate 1 by glycogen synthase kinase 3 impairs insulin action. Proc Natl Acad Sci USA 1997; 94: 9660-9664
    CrossrefPubMedGoogle Scholar
  • 52 Yamamoto M, Toya Y, Jensen RA. et al. Caveolin is an inhibitor of platelet-derived growth factor receptor signaling. Exp Cell Res 1999; 247: 380-388
    CrossrefPubMedGoogle Scholar
  • 53 Ishikawaa Y, Otsua K, Oshikawa J. Caveolin; different roles for insulin signal?. Cell Signal 2005; 17: 1175-1182
    CrossrefPubMedGoogle Scholar
  • 54 Zagoory O, Braiman A, Priel Z. The mechanism of ciliary stimulation by acetylcholine: Roles of calcium, PKA, and PKG. J Gen Physiol 2002; 119: 329-339
    CrossrefPubMedGoogle Scholar
  • 55 Wessler IK, Kirkpatrick CJ. The non-neuronal cholinergic system: An emerging drug target in the airways. Pulm Pharmacol Ther 2001; 14: 423-434
    CrossrefPubMedGoogle Scholar
  • 56 Konig P, Dedio J, Oess S. et al. NOSIP and its interacting protein, eNOS, in the rat trachea and lung. J Histochem Cytochem 2005; 53: 155-164
    CrossrefPubMedGoogle Scholar
  • 57 Krasteva G, Pfeil U, Drab M. et al. Caveolin-1 and -2 in airway epithelium: Expression and in situ association as detected by FRET-CLSM. Respir Res 2006; 7: 108
    CrossrefPubMedGoogle Scholar
  • 58 Li C, Duan W, Yang F. et al. Caveolin-3-anchored microdomains at the rabbit sarcoplasmic reticulum membranes. Biochem Biophys Res Commun 2006; 344: 1135-1140
    CrossrefPubMedGoogle Scholar
  • 59 Krasteva G, Pfeil U, Filip AM. et al. Caveolin-3 and eNOS colocalize and interact in ciliated airway epithelial cells in the rat. Int J Biochem Cell Biol 2007; 39: 615-625
    CrossrefPubMedGoogle Scholar
  • 60 McNally EM, de Sa Moreira E, Duggan DJ. et al. Caveolin-3 in muscular dystrophy. Hum Mol Genet 1998; 7: 871-877
    CrossrefPubMedGoogle Scholar
  • 61 Gazzerro E, Sotgia F, Bruno C. et al. Caveolinopathies: from the biology of caveolin-3 to human diseases. Eur J Hum Genet 2010; 18: 137-145
    PubMedGoogle Scholar
  • 62 Bruning JC, Michael MD, Winnay JN. et al. A muscle-specific insulin receptor knockout exhibits features of the metabolic syndrome of NIDDM without altering glucose tolerance. Mol Cell 1998; 2: 559-569
    CrossrefPubMedGoogle Scholar
  • 63 Eldar-Finkelman H, Schreyer SA, Shinohara MM. et al. Increased glycogen synthase kinase-3 activity in diabetes- and obesity-prone C57BL/6J mice. Diabetes 1999; 48: 1662-1666
    CrossrefPubMedGoogle Scholar
  • 64 Nandi A, Kitamura Y, Accili D. Mouse models of insulin resistance. Physiol Rev 2004; 84: 623-647
    CrossrefPubMedGoogle Scholar
  • 65 Cohen AW, Combs TP, Scherer PE. et al. Role of caveolin and caveolae in insulin signaling and diabetes. Am J Physiol Endocrinol Metab 2003; 285: 1151-1160
    CrossrefPubMedGoogle Scholar
  • 66 Dupuy AM, Mas E, Ritchie K. et al. The relationship between apolipoprotein E4 and lipid metabolism is impaired in Alzheimer’s disease. Gerontology 2001; 47: 213-218
    CrossrefPubMedGoogle Scholar
  • 67 Corder EH, Saunders AM, Strittmatter WJ. et al. Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer’s disease in late onset families. Science 1993; 261: 921-923
    CrossrefPubMedGoogle Scholar
  • 68 Hyman BT, West HL, Rebeck GW. et al. Quantitative analysis of senile plaques in Alzheimer disease: observation of log-normal size distribution and molecular epidemiology of differences associated with apolipoprotein E genotype and trisomy 21 (Down syndrome). Proc Natl Acad Sci USA 1995; 92: 3586-3590
    CrossrefPubMedGoogle Scholar
  • 69 Premkumar DR, Cohen DL, Hedera P. et al. Apolipoprotein E-epsilon4 alleles in cerebral amyloid angiopathy and cerebrovascular pathology associated with Alzheimer’s disease. Am J Pathol 1996; 148: 2083-2095
    PubMedGoogle Scholar
  • 70 Poirier J, Davignon J, Bouthillier D. et al. Apolipoprotein E polymorphism and Alzheimer’s disease. Lancet 1993; 342: 697-699
    CrossrefPubMedGoogle Scholar
  • 71 Simons K, Ikonen E. Functional rafts in cell membranes. Nature 1997; 387: 569-572
    CrossrefPubMedGoogle Scholar
  • 72 Galbiati F, Razani B, Lisanti MP. Emerging themes in lipid rafts and caveolae. Cell 2001; 106: 403-411
    CrossrefPubMedGoogle Scholar
  • 73 Gaudreault SB, Dea D, Poirier J. Increased caveolin-1 expression in Alzheimer’s disease brain. Neurobiol Aging 2004; 25: 753-759
    CrossrefPubMedGoogle Scholar
  • 74 Garrean S, Gao XP, Brovkovych V. et al. Caveolin-1 regulates NF-kappaB activation and lung inflammatory response to sepsis induced by lipopolysaccharide. J Immunol 2006; 177: 4853-4860
    CrossrefPubMedGoogle Scholar
  • 75 Ohnuma K, Inoue H, Uchiyama M. et al. T-cell activation via CD26 and caveolin-1 in rheumatoid synovium. Mod Rheumatol 2006; 16: 3-13
    CrossrefPubMedGoogle Scholar
  • 76 Malkin CJ, Channer KS, Jones TH. Testosterone and heart failure. Curr Opin Endocrinol Diabetes Obes 2010; 17: 262-268
    CrossrefPubMedGoogle Scholar
  • 77 Golden KL, Marsh JD, Jiang Y. et al. Gonadectomy alters myosin heavy chain composition in isolated cardiac myocytes. Endocrine 2004; 24: 137-140
    CrossrefPubMedGoogle Scholar
  • 78 Campelo AE, Cutini PH, Massheimer VL. Testosterone modulates platelet aggregation and endothelial cell growth through nitric oxide pathway. J Endocrinol 2012; 213: 77-87
    CrossrefPubMedGoogle Scholar
  • 79 Ota H, Akishita M, Akiyoshi T. et al. Testosterone deficiency accelerates neuronal and vascular aging of SAMP8 mice: protective role of eNOS and SIRT1. PLoS One 2012; 7: e29598
    CrossrefPubMedGoogle Scholar
  • 80 Marsh JD, Lehmann MH, Ritchie RH. et al. Androgen receptors mediate hypertrophy in cardiac myocytes. Circulation 1998; 98: 256-261
    CrossrefPubMedGoogle Scholar
  • 81 Feron O, Dessy C, Moniotte S. et al. Hypercholesterolemia decreases nitric oxide production by promoting the interaction of caveolin and endothelial nitric oxide synthase. J Clin Invest 1999; 103: 897-905
    CrossrefPubMedGoogle Scholar
  • 82 Marber MS, Latchman DS, Walker JM. et al. Cardiac stress protein elevation 24 hours after brief ischemia or heat stress is associated with resistance to myocardial infarction. Circulation 1993; 88: 1264-1272
    CrossrefPubMedGoogle Scholar
  • 83 Goyal A, Semwal BC, Yadav HN. Abrogated cardioprotective effect of ischemic preconditioning in ovariectomized rat heart. Hum Exp Toxicol 2016; 35: 644-653
    CrossrefPubMedGoogle Scholar
  • 84 Gupta I, Goyal A, Singh NK. et al. Hemin, a heme oxygenase-1 inducer, restores the attenuated cardioprotective effect of ischemic preconditioning in isolated diabetic rat heart. Hum Exp Toxicol 2017; 36: 867-875
    CrossrefPubMedGoogle Scholar